tbuckley/cabot-search huggingface dataset:
Abstract 4464: Ciclopirox Olamine alters PEAK-1-mediated cytoskeleton organization and invasion of metastatic cancer cells
Authors: Jessica M. Weems, Richard L. Klemke
Journal: Cancer Research (2011)

Abstract The majority of cancer patients die from metastatic disease because there are no drugs available to prevent the spread of cancer and eradicate metastases in patients. The antimycotic drug ciclopirox olamine (CPX) is under investigation as a repositioned drug candidate which has anti-tumor and anti-angiogenesis activity in experimental models. Because CPX has been FDA tested and shows exceptionally low side effects in patients even at high doses, it has significant potential as both a therapeutic to prevent cancer recurrence after surgical resection and for the long term systemic treatment of cancer patients with overt metastatic disease. However, CPX has not yet been tested for its ability to inhibit metastatic cell function. In this study we examined the ability of CPX to inhibit metastatic cancer cell migration, invasion, and proliferation, and evaluated the signal transduction pathways that regulate these processes. Interestingly, CPX was observed to inhibit the expression of the tyrosine kinase, pseudopodium-enriched atypical kinase 1 (PEAK1), which is necessary for proper remodeling of the actin cytoskeleton and focal adhesion dynamics in metastatic cancer cells (PNAS, 107(24), 10920-5). Associated with the decrease in PEAK1 expression by CPX was decreased total cellular tyrosine phosphoprotein content, pseudopodium protrusion, cancer cell spreading, movement, and proliferation on extracellular matrix proteins. Collectively, our findings indicate that at therapeutic doses, CPX potently alters cytoskeletal signaling, cancer cell movement, and proliferation by modulating PEAK1 activity. These findings are important in light of the fact that PEAK1 amplification and cytoskeleton modulation have been linked to anchorage-independent cell growth, cell migration, and tumor progression in human gastrointestinal cancers. The exceptional safety record of CPX and our findings support the notion that CPX has significant potential as a repositioned therapeutic agent to combat cancer recurrence and spread in patients. 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 4464. doi:10.1158/1538-7445.AM2011-4464
Treatment of Supraventricular Tachycardia Due to Atrioventricular Nodal Reentry by Radiofrequency Catheter Ablation of Slow-Pathway Conduction
Authors: Warren M. Jackman, Karen J. Beckman, James H. McClelland, Xunzhang Wang, Karen J. Friday, Carlos A. Roman, Kriegh P. Moulton, Nicholas Twidale, H. Andrew Hazlitt, Michael I. Prior, Jess Oren, Edward D. Overholt, Ralph Lazzara
Journal: New England Journal of Medicine (1992)

Atrioventricular nodal reentrant tachycardia (AVNRT), the most common form of supraventricular tachycardia, results from conduction through a reentrant circuit comprising fast and slow atrioventricular nodal pathways. Antiarrhythmic-drug therapy is not consistently successful in controlling this rhythm disturbance. Catheter ablation of the fast pathway with radiofrequency current eliminates AVNRT, but it can produce heart block. We hypothesized that catheter ablation of the site of insertion of the slow pathway into the atrium would eliminate AVNRT while leaving normal (fast-pathway) atrioventricular nodal conduction intact.
Hypercalcemia and Ectopic Secretion of Parathyroid Hormone by an Ovarian Carcinoma with Rearrangement of the Gene for Parathyroid Hormone
Authors: Samuel R. Nussbaum, Randall D. Gaz, Andrew Arnold
Journal: New England Journal of Medicine (1990)

HYPERCALCEMIA accompanied by elevated serum concentrations of parathyroid hormone (PTH) is the cardinal feature of primary hyperparathyroidism. The excessive production of PTH is due most often to a parathyroid adenoma, less often to parathyroid hyperplasia, and rarely to parathyroid carcinoma. In contrast, humoral hypercalcemia of cancer is now recognized to be a syndrome that is not dependent on PTH. Levels of the novel peptide PTH-related peptide are increased in the serum of most patients with squamous carcinoma,1 and through its binding to a common receptor for PTH and PTH-related peptide, it produces the biochemical features of hyperparathyroidism.2 Immunoradiometric assays for . . .
Correlation between kinetic features on breast MRI computer-aided detection (CAD) and prognostic factors of breast cancer.
Authors: H Kim, H Kim, H Shin, J Lee, M Ko, J Moon
Journal: Cancer Research (2009)

Abstract Abstract #4015 The purpose of this study was to correlate the kinetic features of breast MR computer-aided detection (CAD) with the prognostic factors of breast cancer.&amp;#x2028; A total of 65 patients were included in our study from December 2007 to March 2008. We reviewed kinetic features of MR CAD such as proportion of initial rapid rise enhancement, percentage of washout, and enhancement patterns. We also recorded prognostic factors such as tumor size, estrogen receptor, progesterone receptor, HER-2/neu status, lymphovascular invasion, and histologic grade on pathology. We correlated the kinetic features on MR CAD with prognostic factors. Pearson and Spearman correlation test were used to evaluate correlation between kinetic features and tumor size. Fisher exact test also used for the statistical analysis between kinetic features and other prognostic factors.&amp;#x2028; In 65 cases, 59 cases showed rapid washout enhancement patterns, 5 cases showed rapid plateau pattern and only one case showed medium plateau. Tumor size showed correlation with the initial rapid rise enhancement (p=0.03) on Pearson correlation test and the delayed washout percentage (p=0.05) on Spearman correlation test.&amp;#x2028; Positive progesterone receptor status was significantly associated with rapid early enhancement (p=0.023) and delayed washout (p=0.05), respectively. HER-2/neu status showed trend with the early enhancement (p=0.063). Other prognostic factors such as estrogen receptor, lymphovascular invasion and histologic grade showed no significant correlation with the kinetic features on MR CAD.&amp;#x2028; Several kinetic features on MR CAD were correlated with the specific prognostic factors of breast cancer. Recognition of several kinetic features correlated with prognostic factors might help to predict of patients' prognosis and to decide the treatment plan. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4015.
Abstract 3692: Single center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver predominant metastatic colorectal adenocarcinoma after failure of 1st-line combination chemotherapy
Authors: Eric J. Roeland, Shakeela Dad, Kelly Shimabukuro, Paul Fanta, Steven Rose, Tony Reid
Journal: Cancer Research (2012)

Abstract Background: Colorectal cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death. Liver metastases develop in half of all the colorectal cancer (CRC) cases and cause death in ∼90% of patients. We are evaluating the treatment of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using Yttrium-90 radioactive microspheres for subjects with liver progressive disease following failure of first-line FOLFOX (± bevacizumab). We are presenting our preliminary data for the phase II study evaluating the tumor response rates, PFS, and long-term safety and toxicity to SIRT following FOLFOX (± bevacizumab) prior to FOLFIRI. Methods: Subjects with predominantly hepatic metastatic CRC whose disease progressed on first-line FOLFOX (± bevacizumab) based therapy are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives their SIRT treatment(s) followed by second-line FOLFIRI based therapy 4-6 weeks after the final SIRT treatment. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. Results: To date, 9 metastatic CRC subjects have been treated and 11 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. Four of 8 subjects (50%) achieved PFS at 6 months and average TTP is 6.7 months (0.7-17.3 months). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (Subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 months median PFS. In 8 subjects with predominant liver metastatic CRC, we have observed 50% PFS at 6 months. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy. 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 3692. doi:1538-7445.AM2012-3692
Improving Adjuvant Therapy for Rectal Cancer by Combining Protracted-Infusion Fluorouracil with Radiation Therapy after Curative Surgery
Authors: Michael J. O'Connell, James A. Martenson, Harry S. Wieand, James E. Krook, John S. Macdonald, Daniel G. Haller, Robert J. Mayer, Leonard L. Gunderson, Tyvin A. Rich
Journal: New England Journal of Medicine (1994)

The combination of radiation therapy and chemotherapy with fluorouracil plus semustine after surgery has been established as an effective approach to decreasing the risk of tumor relapse and improving survival in patients with rectal cancer who are at high risk for relapse or death. We sought to determine whether the efficacy of chemotherapy could be improved by administering fluorouracil by protracted infusion throughout the duration of radiation therapy and whether the omission of semustine would reduce the toxicity and delayed complications of chemotherapy without decreasing its antitumor efficacy.
Abstract 5177: Assessment of EpCAM function in lung cancer progression
Authors: Han Jee Seung, Youngwook Kim, Keunchil Park, Myung-ju Ahn
Journal: Cancer Research (2010)

Abstract The epithelial cell adhesion molecule (EpCAM) is expressed on the basolateral membrane of the majority of epithelial tissues and it is upregulated or expressed de novo in various carcinomas. Several studies showed that high level EpCAM expression is associated with poor survival and tumor grading. EpCAM remains an attractive cancer therapeutic target. Until recently, however, molecular impact of EpCAM on cancer signaling processes and growth regulation has not been clearly understood. We show here that inhibition of EpCAM by inducible shRNA resulted in a change of cell cycle profile and decreased cellular proliferation in non-small cell lung cancer cells. Cancer cells were apparently arrested in G1 phase, and subsequent western blotting experiments showed that p27 protein increased upon EpCAM inhibition. To test whether EpCAM depletion would also lead to changes in tumor progression in vivo, we assessed the effect of EpCAM shRNA induction in lung cancer animal xenograft model. EpCAM knock-down led to almost complete tumor progression in vivo. Additional studies showed that inhibition of EpCAM expression was related to decreased microvessel density, revealed by CD31 immunohistochemical staining. Overall, the data presented here suggest that EpCAM can be another therapeutic target of lung cancer. Development of inhibitory modality of EpCAM function needs to be tested further alone or in combination of other therapeutic reagents. 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 5177.
Abstract P4-11-20: Integration of SPECT/CT Lymphoscintigraphy into Breast Cancer Radiation for Lymphatic Sparing
Authors: AL Cheville, IA Petersen, DH Brinkman, SB Ward, BP Mullan, J Durski, MK O'Connor, PJ Schomberg, E Yan, YI Garces, NN. Laack
Journal: Cancer Research (2010)

Abstract Lymphedema (LE) is a common complication of cancer treatment, and has been identified as the number one issue by breast cancer survivors with incidence as high as 70%. Given the long-term survivorship of these women, LE is a widely prevalent condition. Irradiation of axillary and supraclavicular lymph nodes increases a patient's risk of LE onset and progression by as much as 2-fold. It is anticipated that a more individualized approach to post-surgical irradiation of breast cancer patients may reduce radiation-induced lymph node (LN) damage without sacrificing control rates, although it is noted that a definitive radiation exposure threshold below which LNs physiological integrity will be preserved is currently lacking. To identify the locations of the small, non-pathological but physiologically relevant LNs which drain the arm after breast cancer surgery and incorporate them into radiation planning, filtered 99mTc sulfur colloid (TcSC) was administered and a SPECT-CT scan was acquired for 22 patients immobilized in the treatment position. These images were registered with the Radiation Oncology planning CT scan, and draining LN were contoured automatically using a threshold of 50% maximum intensity. Two treatment plans were generated for each patient, one per routine clinical practice (STD) and the other (MOD) with treatment fields modified to minimize dose to the LNs visible on SPECT/CT images while ensuringthat ≥50Gy or biologic equivalent is delivered to target tissues. 53 draining LN were identified, 54% of which were inside the STD plan fields but could be blocked in the MOD plan fields. 62% of LN in the STD plans vs. 17% in the MOD plans receiving a mean of ≥10Gy, and 27% in the STD plans vs. 6% in the MOD plans receiving a mean of ≥40Gy. Patient-specific LN dose reduction can be achieved through integration of SPECT/CT images into the radiation planning process. These patients will be followed for the development of LE, to estimate an exposure threshold below which LN preservation is assured. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-20.
AB0856 Real-life effectiveness of infliximab in the treatment of ankylosing spondylitis over 3 years: The canadian experience
Authors: P. Rahman, W. Bensen, S. Shaikh, N. Longo, J. Sampalis, S. Otawa, S. Khalil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Ankylosing Spondylitis (AS) is a chronic inflammatory disorder affecting as much as 1% of the general population.<sup>1</sup> The efficacy of Infliximab in the management of AS has been demonstrated in several controlled clinical trials with limited follow-up periods. Longitudinal observational studies assessing real-life effectiveness of anti-TNF agents are essential in order to demonstrate the true benefits. The objective of this study was to assess in Canadian clinical practice the 36-month outcomes in patients with AS treated with Infliximab. <h3>Methods</h3> The data for this analysis were obtained from BioTRAC, an observational prospective registry of adult AS patients initiated on treatment with Infliximab since 2005 and managed as per routine care. Patients enrolled were biologic-naïve or had initiated treatment with a biologic for a period of &lt;6 months prior to enrolment. <h3>Results</h3> A total of 204 AS patients who had at least one follow-up assessment were included in this analysis, with a mean age of 46 years and mean disease duration since diagnosis of 10.6 years. Among these, 148, 83, and 46 had a 12-, 24-, and 36-month assessment, respectively. At the time of enrollment in the registry, mean (SD) patient parameters were: C-reactive protein (CRP) =1.7 (1.9) mg/dL, erythrocyte sedimentation rate (ESR) =26.9 (20.5) mm/hr, morning stiffness =75.9 (39.3) mins, health assessment questionnaire (HAQ) =1.1 (0.6), physician global assessment of disease activity (PGA) =67.2 (18.1), BASDAI =6.5 (2.1), BASFI =6.2 (2.4), and ASDAS =3.8 (0.9). By 6 months of treatment significant improvements (P&lt;0.05) were observed in all clinical and patient outcome parameters studied, which were sustained over 36 months of treatment. By 6, 12, 24, and 36 months 58%/68%/76%/84% and 30%/38%/48%/45%, achieved Clinically Important Improvement in ASDAS (Δ≥1.1) and ASDAS Major Improvement (Δ≥2.0), respectively. The proportion of patients with very high disease activity (ASDAS &gt;3.5) decreased from 64.2% at baseline to 7.9% at 36 months. <h3>Conclusions</h3> The results of this Canadian, longitudinal, real-life observational study demonstrate that treatment with infliximab over three years is effective in reducing symptom severity and improving outcomes in patients with ankylosing spondylitis. <h3>References</h3> Elyan M, Khan MA. Diagnosing ankylosing spondylitis. J Rheumatol 2006;33 Suppl 78:12-23. <h3>Disclosure of Interest</h3> None Declared
Abstract 218: R-Spondin (RSPO) signaling drives the growth of multiple human tumor types.
Authors: Austin Gurney, Cecile Chartier, Fumiko Axelrod, Jennifer Cain, Wan-Ching Yen, Christopher Murriel, Janak Raval, Marcus Fischer, Jalpa Shah, May Ji, Christopher Bond, Ann Kapoun, John Lewicki, Timothy Hoey
Journal: Cancer Research (2013)

Abstract The R-spondin-LGR signaling axis is a recently appreciated pathway that promotes beta-catenin signaling in normal stem cell populations. Beta-catenin signaling had long been considered synonymous with Wnt signaling. We conducted a reporter-based screen for secreted beta-catenin signaling activities produced by a panel of human tumors. This exercise and further molecular characterization efforts discovered RSPO activity produced by numerous human tumors of multiple tumor types including ovarian, pancreatic, colon, breast and non-small cell lung cancer. Specific antibody antagonists of RSPO family members were developed. In minimally passaged human tumor xenograft models, anti-RSPO treatment markedly inhibited tumor growth in several tumor types. Moreover, RPSO blockade promoted tumor differentiation and reduced the frequency of tumor initiating cells. These data highlight the potential for therapeutic intervention with this newly appreciated signaling axis. Citation Format: Austin Gurney, Cecile Chartier, Fumiko Axelrod, Jennifer Cain, Wan-Ching Yen, Christopher Murriel, Janak Raval, Marcus Fischer, Jalpa Shah, May Ji, Christopher Bond, Ann Kapoun, John Lewicki, Timothy Hoey. R-Spondin (RSPO) signaling drives the growth of multiple human tumor types. [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 218. doi:10.1158/1538-7445.AM2013-218
Riociguat for Pulmonary Hypertension — A Glass Half Full
Authors: Stephen L. Archer
Journal: New England Journal of Medicine (2013)

In this issue of the Journal, Ghofrani et al. assess riociguat, a soluble guanylate cyclase stimulator, as an oral therapy for two forms of pulmonary hypertension. The Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (CHEST-1)1 and the Pulmonary Arterial Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (PATENT-1)2 are international, multicenter, randomized, placebo-controlled, clinical trials that enrolled patients with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension, respectively.The World Health Organization (WHO) classification recognizes five groups of disorders that cause pulmonary hypertension. Pulmonary vascular obstruction is the prime pathologic feature in both pulmonary arterial hypertension (Group 1) and chronic . . .
IN VIVO MAGNETIC RESONANCE TRACKING OF MESENCHYMAL STROMAL CELLS LABELED WITH ULTRA-SMALL PARAMAGNETIC IRON OXIDE PARTICLES AFTER INTRAMYOCARDIAL INJECTION IN PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Anders Bruun Mathiasen, Erik Jørgensen, Steffen Helqvist, Annette Ekblond, Kishore Bhakoo, Carsten Thomsen, Jens Kastrup
Journal: Journal of the American College of Cardiology (2016)
Hemolytic Anemia after Open-Heart Repair of Ostium-Primum Defects
Authors: Thomas A. Verdon, Ralph H. Forrester, William H. Crosby
Journal: New England Journal of Medicine (1963)

DESTRUCTION of red cells by mechanical battering during circulation may result in hemolytic reactions, with hemoglobinemia and, if severe enough, hemoglobinuria. Prolonged, strenuous exertion has provoked the syndrome,1 , 2 and it has recently occurred in two other situations associated with cardiovascular surgery: after the insertion of a lucite ball-valve prosthesis within the thoracic aorta3; and as a complication of cardiac repair after open-heart surgery.4 The purpose of this report is to present 2 further cases of the second syndrome illustrating two degrees of severity of hemolytic disease.Case ReportsCase 1. A 17-year-old boy was admitted to Walter Reed General . . .
PTH-037 Do Patients with a Previous Negative Colonoscopy and Positive Fob Test Need a Bowel Cancer Screening Colonscopy?
Authors: K Sahnan, P G Vaughan-Shaw, R Valori
Journal: Gut (2013)

<h3>Introduction</h3> Patients with a positive faecal occult blood test invited for screening colonoscopy may have undergone previous colonoscopy. Excluding such patients from a repeat colonoscopy may reduce endoscopy waiting lists and avoid repeated and unnecessary invasive investigations. This study investigates the prevalence of previous colonoscopy in Bowel Cancer Screening Programme (BCSP) patients and considers whether repeat colonoscopy is required. <h3>Methods</h3> All patients undergoing BCSP colonoscopy over a 30-month period at our unit were identified and cross-referenced against colonoscopy records for the preceding 3 years. New diagnoses of colorectal cancer in the cohort were identified and cancer yield in those with and without recent colonoscopy compared using the chi-squared test. <h3>Results</h3> 1419 BCSP colonoscopies were performed in 1339 patients over the study period. 109 colonoscopies were repeats with median interval to repeat 378 days. Indication for prior colonoscopy included prior BCSP invitation (n = 90), polyp surveillance (n = 6) and symptoms (n = 13). There were 111 diagnoses of colorectal cancer in the cohort but no patient with a previous colonoscopy was found to have colorectal cancer. Cancer yield in first time BCSP colonoscopy was greater than in repeated colonoscopy (8% <i>vs.</i> 0% p = 0.002). <h3>Conclusion</h3> Cancer yield is reduced in BCSP patients with a recent negative colonoscopy. Excluding such patients would reduce pressure on endoscopy units and any morbidity associated with repeat colonoscopy. However, such an approach would be associated with a small risk of missed pathology. Larger studies are required to define the safety of this approach and inform national guidance. <h3>Disclosure of Interest</h3> None Declared.