tbuckley/cabot-search huggingface dataset:
Abstract 3882: Myb contributes to pancreatic cancer growth and metastasis.
Authors: Sanjeev K. Srivastava, Seema Singh, Arun Bhardwaj, Sumit Arora, Steven McClellan, William E. Grizzle, Ajay P. Singh
Journal: Cancer Research (2013)

Abstract Pancreatic cancer (PC) is a disease of insidious progression. In most cases, it is diagnosed late at a stage when it is either locally advanced or has already metastasized to distant sites, resulting in a poor prognosis of the patients. Therefore, there is an urgent need to identify novel molecular targets regulating PC progression and metastasis, so that an effective treatment strategy can be developed against this devastating disease. In this study, we investigated the role of Myb in pancreatic cancer pathogenesis. Myb/c-Myb, a cellular progenitor of v-Myb oncogenes, is amplified in a sub-set of PC and encodes for a transcription factor. Myb confers its oncogenic activity by regulating the expression of several target genes. To examine the pathological significance of Myb in pancreatic cancer, we silenced its expression in Myb-overexpressing pancreatic cancer cell lines (Panc1 and MiaPaCa), and ectopically overexpressed it in a poorly-tumorigenic low Myb-expressing cell line (BxPC3). Our data showed that short-hairpin RNA (shRNA)-mediated stable silencing of Myb in Panc1 and MiaPaCa cells led to diminished growth and clonogenic ability as compared to their respective scrambled-transfected control cells. Furthermore, Myb-silenced Panc1 and MiaPaCa cells also exhibited reduced, motility and invasion as compared to their respective controls. Accordingly, enhanced growth, clonogenicity, motility and invasion were observed in Myb-overexpressing BXPC3 cells as compared to vector only-transfected cells. Immunoblot analyses demonstrated altered expression of cell cycle- and apoptosis- associated proteins in Myb-silenced and overexpressing pancreatic cancer cells. Moreover, loss of mesenchymal and gain of epithelial markers was observed in Myb-silenced Panc1 and MiaPaCa cells, whereas Myb overexpressing BXPC3 cells exhibited an opposite pattern. These changes were also associated with actin reorganization, thus suggesting a role of Myb in epithelial to mesenchymal transition (EMT) of PC cells. In vivo studies in orthotopic mouse model of pancreatic cancer demonstrated decreased tumor growth and metastasis of the Myb- silenced MiaPaCa cells, while an increase was observed in Myb-overexpressing BXPC3 cells as compared to their respective control cells. Altogether, our studies provide the first experimental evidence for a functional role of Myb in progression and metastasis of pancreatic cancer. Citation Format: Sanjeev K. Srivastava, Seema Singh, Arun Bhardwaj, Sumit Arora, Steven McClellan, William E. Grizzle, Ajay P. Singh. Myb contributes to pancreatic cancer growth and metastasis. [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 3882. doi:10.1158/1538-7445.AM2013-3882
Abstract 537: Mechanisms by which pantoprazole, a proton pump inhibitor, enhances the activity of doxorubicin in solid tumors
Authors: Qian Tan, Krupa Patel, Carol M. Lee, Junyan Zhang, Anthony Joshua, Marianne Koritzinsky, Bradly G. Wouters, Ian F. Tannock
Journal: Cancer Research (2011)

Abstract Purpose: Mechanisms of tumour resistance to cytotoxic drugs in solid tumours include limited drug distribution from tumour blood vessels and other effects of the tumour microenvironment. Proton pump inhibitors, such as pantoprazole (PTP), raise endosomal pH and thereby decrease sequestration of basic drugs in acidic compartments. This may allow more drugs to interact with DNA, while decreased net cellular uptake of drug, may allow more drugs to penetrate tissue to distal cells. PTP might also inhibit autophagy, a possible target for anticancer therapy, since endosomes are important intermediaries of this process. Here we describe the effects of PTP on doxorubicin uptake and distribution in cell cultures and solid tumours, and effects to cause growth delay. We have also evaluated the effect of PTP on autophagy of tumour cells. Methods: Endosomal pH of cells was measured by using Lysosensor and fluorescence spectroscopy. Cytotoxicity was evaluated by a colony-forming assay. Doxorubicin distribution was quantified in MCF-7 xenografts by immunohistochemistry, in relation to blood vessels (recognized by an antibody to CD31), and regions of hypoxia (recognized by an antibody to EF5), with and without pre-treatment with PTP. Anti-tumour effects were evaluated by growth delay following treatment with single or multiple doses of doxorubicin with and without PTP. Effects of PTP on autophagy were evaluated by (i) expression of the LC3II protein by Western blotting and (ii) effects of PTP on prostate cancer PC3 cells transfected with green fluorescent protein) and with LC3 protein (a marker of autophagy) tagged with red fluorescent protein (mRFP-GFP-LC3 cells) Results: PTP increased endosomal pH and decreased endosomal sequestration of doxorubicin in cultured cells. Pre-treatment with PTP increased the distribution of doxorubicin in solid tumours. PTP alone had no effect on tumour growth but increased the effect of doxorubicin to cause growth delay of human tumour xenografts with no apparent increase in toxicity. PTP showed marked effects to inhibit autophagy in cultured tumour cells in a dose and time dependent manner. Conclusions/Discussion: PTP increases the effectiveness of doxorubicin against solid tumours and this combination is being investigated in a phase I clinical trial. Potential mechanisms underlying this effect include inhibition of sequestration of doxorubicin in endosomes permitting better drug distribution, and inhibition of autophagy. Supported by a research grant from the Canadian Institutes of Health Research 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 537. doi:10.1158/1538-7445.AM2011-537
Masters and Johnson on Sex and Human Loving
Authors: Domeena C. Renshaw
Journal: JAMA (1987)

Pioneering sex researchers William Masters, MD, and Virginia Johnson (later to become Mrs Masters) have written<i>Human Sexual Responses</i>(1966) and<i>Human Sexual Inadequacy</i>(1970). Although their impact was dramatic, these two books were stylistically severe and were dubbed "least read bestsellers." The same cannot be said for their latest contribution, co-authored also by Robert Kolodny, MD. <i>Sex and Human Loving</i>is 600 pages of enjoyable reading. It is filled with helpful information for both clinicians and patients on intimate human relationships and sexuality. The illustrations included are of practical value. The anatomy, physiology, problems, dysfunctions, and treatments of male and female sexuality from childhood to late age are skillfully covered. Furthermore a useful index makes these discussions easily accessible. Contraception, sexually transmitted diseases, homosexuality, varieties of sexual behavior, coercive assault, sexual fantasy, solitary sexual behavior, love, communication skills, and intimacy are each given a chapter. A three-page subsection on
Reply to Gyökeres et al.
Authors: S. Wada
Journal: Endoscopy (2002)

We are grateful to Dr. Gyökeres and his colleagues for their comments on our recent report, to which we would like to reply here. The merit of the O-ring ligation method is that cutting and sampling are both simple. We believe the risk of bleeding with this method differs little from that with the conventional endoscopic incision. With regard to aspiration and ligation, we cannot see that there is any risk when the cyst has sufficient underlying space.
Abstract 4714: Oral human papillomavirus infection among HIV infected and uninfected men who have sex with men
Authors: Daniel C. Beachler, Lisa P. Jacobson, Joseph B. Margolick, Maura L. Gillsion, Gypsyamber D'Souza
Journal: Cancer Research (2010)

Abstract Introduction: Human papillomavirus (HPV) causes a subset of oropharyngeal cancers but the prevalence and risk factors for oral HPV infection are not well understood. Initial studies suggest HIV-infected individuals have an increased incidence of HPV-related cancers including oropharyngeal cancer. Methods: Oral exfoliated cells were collected using a swish and gargle with 10ml of Scope mouthwash in 149 HIV-infected and HIV-uninfected men who have sex with men (MSM) in the Baltimore center of the MACS. Samples were tested for 37 types of HPV DNA using PGMY09/11 consensus primers and line blot hybridization. Logistic regression was used to explore risk factors for infection. Results: Prevalent oral HPV infection was common among the 62 HIV-infected and the 87 HIV-uninfected MSM (39% vs 28%, p=0.15). HPV16 was the most common HPV type detected and was found in an alarming 13% of MSM (8.2% of HIV-infected and 16% of HIV-uninfected MSM, p=0.15). The most common other oncogenic oral HPV infections detected were HPV 66, 68, 83 (2.0% prevalence each), and 45, 53, 58, 59, 73 (1.3% each). In this study 32% of men reported multiple oral sex partners in the past six months. Oral HPV16 prevalence was significantly associated with number of recent oral sexual partners among HIV uninfected (p-trend=0.04) but not HIV infected participants. The majority of HIV-infected participants were currently on HAART (74%), had CD4 cell count&amp;gt;500 (65%) and HIV viral load &amp;lt;500 copies/ml (78%). Oral HPV prevalence was similar among current HAART users (41%) compared to former or never HAART users (27% and 40% respectively) and prevalence increased non-significantly with low CD4 and high HIV viral load. In multivariate analysis of HIV infected but not HIV-uninfected MSM, current marijuana users were over ten times more likely (OR=11.5 95%CI=1.5-17) to have prevalent high risk HPV infection. Conclusions: Oral HPV16 prevalence is high among both HIV uninfected and HIV infected MSM suggesting they may be at increased risk for HPV-associated oropharyngeal cancers. Oral HPV risk factor profiles differed by HIV status. Oral HPV prevalence was similar among HIV infected HAART users and non-users suggesting HAART may not improve oral HPV clearance. 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 4714.
Early Assessment of Metabolic Response by 18F-FDG PET During Concomitant Radiochemotherapy of Non–Small Cell Lung Carcinoma Is Associated With Survival
Authors: Séna Yossi, Samar Krhili, Jean-Pierre Muratet, Anne-Lise Septans, Loïc Campion, Fabrice Denis
Journal: Clinical Nuclear Medicine (2014)

We performed a retrospective single-center study to assess if midtreatment 18F-FDG PET/CT could predict local control and survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.Thirty-one consecutive patients with unresectable or locally advanced lung cancer (T2-4 N0-3 M0) were treated with concurrent chemoradiotherapy in our center. Each patient received 18F-FDG PET/CT before treatment and at midtreatment time when a radiation therapy dose of 30 Gy was delivered. We assessed several PET/CT parameters as follows: SUV max, ΔSUV mean, ΔSUV max, variation of hypermetabolic tumor volume, and the variation of tumor total lesion glycolysis (ΔTLG). Univariate analysis was performed, and a stepwise procedure was used to define final multivariate model.The ΔTLG was statistically correlated to overall survival (OS) (P = 0.035), progression-free survival (P = 0.023), and local control (P = 0.043) in univariate analysis. A decrease in TLG over 15% was statistically correlated to a better OS (P = 0.007; hazards ratio [HR], 7.439; 95% confidence interval [CI], 1.168-28.897) and progression-free survival (P = 0.010; HR, 5.695; 95% CI, 1.506-21.537) in univariate analysis. In multivariate analysis, ΔTLG superior to -15% was significantly correlated to a worse OS (P = 0.020; HR, 5.973; 95% CI, 1.324-26.953).Early assessment of TLG response by 18F-FDG PET/CT during concomitant radiochemotherapy of non-small cell lung cancer might be associated with survival.
PTU-257 “Trials and tribulations of setting up an anaesthetist led day-case endoscopy list”
Authors: S V Murugesan, M Davies, N Haslam, H L Smart, S Sarkar
Journal: Gut (2012)

<h3>Introduction</h3> Endoscopy in UK is performed under conscious sedation in daycase (DC) endoscopy units. Patients intolerant of the procedure subsequently undergo the procedure under a general anaesthetic in operating theatres. However whether this service could be effectively offered in a “non-operating theatre room” setting through an anaesthetist-led sedation service (ALS) is not well established within the UK. <h3>Aim</h3> To evaluate a new provision of an ALS in a day case endoscopy unit. <h3>Methods</h3> Service evaluation audit (June–August 2011) of a new weekly dedicated ALS at the Royal Liverpool Hospital was performed. Administrative, anaesthetic and case records and satisfaction scores (1=unsatisfactory; 5=fully satisfied; patients, anaesthetists, endoscopists) and “patient journey” was evaluated. <h3>Results</h3> <b>Administration</b>: Three cases were scheduled per listed. Waiting time was a median 9 weeks compared to a median 6 weeks for other lists. Of the 25 patients listed, only 20 (80%) had a procedure. DNA rate was 16% and cancellation rate 4%. <b>Patients and Indication</b>: Median age was 53 years (range 18–80 years), median ASA was 2 (range 1–3), 8 (42%) were female. 20 underwent propofol assisted endoscopy (7 colonoscopy, 8 HALO<sup>®</sup>, 3 ERCP, 1 OGD and 1 EUS). <b>Procedural details</b>: ALS was provided by a consultant anaesthetist assisted by operating theatre personnel and endoscopic procedures by a consultant gastroenterologist. All were successfully completed (mean duration of 33 min, range 20–70 min). Modification of anaesthetic equipment was required in all but one and additional equipment had to be borrowed in all. Adverse events were minor (rate 10%)—transient hypoxia (not required ventilation) and hypotension. All patients were discharged successfully as DC. 7-day readmissions and 30-day mortality was 0. The median satisfaction score was 5 (range 4–5) for patients, 5 (range 4–5) for anaesthetists and 5 (3–5) for endoscopists. The additional cost for provision of such a service included the services of the anaesthetist (one programmed activity) and OTP and for drugs (propofol). <h3>Conclusion</h3> Deep sedation for selected endoscopic procedures can be safely and efficiently provided through a dedicated anaesthetist-led list in a remote endoscopy unit. However, waiting times were longer than other lists and a significant number of patients DNA9d/cancelled. We are now setting up pre-assessment clinics and increasing the number of lists to improve the service further. <h3>Competing interests</h3> None declared.
Abstract 5529: Fluorescence-guided navigation surgery for resection of human glioma in an orthotopic model in nude mice
Authors: Masashi Momiyama, Yukihiko Hiroshima, Atsushi Suetsugu, Yasunori Tome, Sumiyuki Mii, Shuya Yano, Michael Bouvet, Takashi Chishima, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract Malignant glioma tumors are the most common primary central nervous system tumors and they are very difficult to completely resect due to their invasive margins. In this study, we compared fluorescence-guided and standard bright-light resection. U87-RFP human glioma cells (2 x 105) were injected stereotactically into the nude mouse brain through a craniotomy open window. Two weeks after tumor-cell inoculation, brain tumors were resected under fluorescence guidance or under bright light. U87-RFP tumors were clearly visualized under fluorescent microscopy with long working distance at the single cell level. Almost all cancer cells were removed using fluorescence-guided navigation without damage to the brain tissue. However, brain tumors were difficult to visualize under bright light and many residual cancer cells remained in the brain after surgery. These results suggest that fluorescence-guided surgery has significant potential for treatment of brain cancer. 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 5529. doi:1538-7445.AM2012-5529
Evaluating the Learning Curve of Magnetic Resonance Imaging (MRI) as a Predictive Tool in Locally Advanced Rectal Cancer (RC) - a Retrospective 12-Year Experience
Authors: Coleman Niamh, Jayaram Anuradha, Connell Louise, Mohamad Rom Fatimah, Keegan Niamh, Harrold Emily, Lee ChaLen, Mehigan Brian, Kennedy Michael John
Journal: Annals of Oncology (2014)
FRI0463-HPR Correlation between self reported physical activity and outcome expectations of physical activity on health and symptoms in patients with rheumatoid arthritis
Authors: G. Wettermark, C.H. Opava
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Physical inactivity in patients with rheumatoid arthritis (RA) is a major problem with increased risks of co-morbidity and premature death. In order to address this problem we need more knowledge on factors that could change sedentary behavior and promote physical activity. <h3>Objectives</h3> The aim of this study was to investigate whether there is a correlation between self rated physical activity and outcome expectations of physical activity (OEPA) regarding health and symptoms of RA. <h3>Methods</h3> Demographics and disease-related data, data on self rated physical activity with the International Physical Activity Questionnaire (IPAQ) and outcome expectations of physical activity (OEPA) were collected from 3152 (2309 women and 843 men) patients with RA. Patients were independent in daily life, Health Assessment Questionnaire (HAQ) &lt;2, had a median age of 62 (range 18-75), and relatively low disease activity with a median disease activity score (DAS 28) of 2.82 (range 0.15-7.62). OEPA were measured with two study-specific questions on expectations of benefits of physical activity on (i) general health and on (ii) symptoms of RA respectively. The two questions were answered on numerical rating scales (1 to 10). Correlations were analyzed with Spearman's rank correlation coefficient. <h3>Results</h3> Analyses showed high scores on the two OEPA- questions, median 10 (range 1-10) and median 8 (range 1-10) respectively. Moderate or high intensity physical activity performance were both reported as median 3 (range 0-7) days per week. No correlations (r ≤0.09) were found between physical activity at moderate or high intensities and Outcome expectations regarding either general health or symptoms of RA. <h3>Conclusions</h3> In conclusion our results indicate that patients with RA in Sweden are well aware of the benefits and positive effects of physical activity on long-term health as well as on the symptoms of RA. However, we found no correlation between outcome expectations of physical activity and self-reported physical activity. The role of outcome expectations in motivating patients to be more physically active is still unclear and more situation specific scales are needed to study this further. <h3>Disclosure of Interest</h3> None Declared
Abstract 1294: Identification of the binding domains that allow ligand-independent co-activation of androgen receptor by Gli2.
Authors: Na Li, Mengqian Chen, Ralph Buttyan
Journal: Cancer Research (2013)

Abstract Gli proteins are transcription factors that mediate the cellular response to Hedgehog signaling. Gli activity guides cell fate decisions during development and is required for the proper morphogenesis of embryonic tissues, including the prostate gland. Previously, we showed that exogenous overexpression of Gli1 or Gli2 in androgen-deprived LNCaP cells increased the expressions of androgen-dependent genes in prostate cancer (PCa) cells and conferred androgen-independent growth behavior to them (Chen et al., Mol Cancer, 9: 89-101, 2010). We also showed that Gli1 or Gli2 proteins co-immunoprecipitate with AR, suggesting that AR interacts with Gli proteins to mediate these effects. Based upon this data, we proposed that Gli1/2 proteins are ligand-independent co-activators of AR in PCa. To better understand the Gli2-AR interaction and its effects on PCa responsiveness to androgen ablation, we fine mapped the specific interaction domains between Gli2 and AR. Complete or partial recombinant Gli2 cDNAs were tagged with GST and the GST-tagged proteins were purified on glutathione beads prior to incubation with in vitro translated human AR protein fragments. GST pulldown assays showed that GLI2 specifically recognizes and binds the Tau5 region within the AR N-terminal domain (AA 391-555). Likewise, AR binds to Gli2 within an extended C-terminal domain (AA 628-1091) that may involve two distinct AR binding sites. AR co-activation studies in 293T cells shows that the presence of binding site(s) and the Gli2 activation domain are required for Gli2 co-activation of AR. Gli2 was tested for its ability to co-activate natural truncated variants of the AR. The interaction of Gli2 with the Tau4 domain of AR was consistent with the ability of Gli2 to co-activate truncated variants of the AR that lack the DNA binding domain. Our work demonstrates that Gli2 co-activation of AR requires direct interaction between the tau5 domain in the AR N-terminus and the AR binding domains in the Gli2 C-terminus as well as the Gli2 activation domain. Gli2 binding at tau5 supports co-activation of the wildtype AR (in both the presence and absence of androgen) as well as co-activation of truncated receptors that do not bind androgens. As such, the evidence that Gli2 expression is increased in PCa by androgen ablation suggests that it may be a factor in progression to castration resistant PCa. Supported by the DOD PCRP (W81XH-10-1-0493, to RB). Citation Format: Na Li, Mengqian Chen, Ralph Buttyan. Identification of the binding domains that allow ligand-independent co-activation of androgen receptor by Gli2. [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 1294. doi:10.1158/1538-7445.AM2013-1294
Calcium-Antagonist Drugs
Authors: Darrell R. Abernethy, Janice B. Schwartz
Journal: New England Journal of Medicine (1999)

Drugs classified as calcium antagonists or calcium-channel blockers were introduced into clinical medicine in the 1960s and are now among the most frequently prescribed drugs for the treatment of cardiovascular diseases.1 Although the currently available calcium antagonists are chemically diverse, they share the common property of blocking the transmembrane flow of calcium ions through voltage-gated L-type (slowly inactivating) channels.2 These drugs have proved effective in patients with hypertension, angina pectoris, and cardiac arrhythmias and may be beneficial in patients with left ventricular diastolic dysfunction, Raynaud's phenomenon, migraine, preterm labor, esophageal spasm, and bipolar disorders.L-Type Calcium ChannelsAll calcium antagonists . . .