tbuckley/cabot-search huggingface dataset:
Abstract 368: MUC1-targeted gold nanoparticle-based theranostic approach
Authors: Brian P. Danysh, Pamela E. Constantinou, Ekaterina Lukianova-Hleb, Russell Broaddus, Daniel D. Carson
Journal: Cancer Research (2011)

Abstract MUC1 is a large transmembrane glycoprotein, extending 200-400 nm from the apical surface of normal polarized epithelial cells in a variety of mucosal tissues. The large ectodomain contains a series of heavily glycosylated tandem repeats and serves as a protective barrier to enzymatic degradation and microbial attack, as well as prevents embryo attachment during the non-receptive phase in the uterus. Many cancers, including endometrial carcinomas, overexpress MUC1 which is believed to promote tumor progression by protecting tumor cells from the immune system, inhibiting apoptosis, and increasing resistance to various chemotherapeutic agents. The availability of MUC1 glycoform-specific antibodies creates an opportunity to exploit the increased or aberrant MUC1 expression in carcinoma cells by creating MUC1-targeted therapies. Gold nanoparticles (AuNPs) conjugated to a human MUC1 ectodomain specific antibody (214D4) are readily endocytosed by MUC1 expressing human endometrial cells (HES) in vitro and, following exposure to a short laser pulse, can be used to form transient vapor bubbles (plasmonic nanobubbles) capable of destroying a cell by mechanically disrupting the cell membrane. In this work, we compare the selective targeting capabilities of MUC1-targeted AuNPs using the human endometrial epithelial cell line HES and endometrial carcinoma cell lines HEC1A and HEC1B. In addition, we have used human MUC1-expressing transgenic mouse lines to examine the feasibility of using AuNP-214D4 targeting in mouse endometrium. These results demonstrate the potential use of MUC1-targetted AuNPs to detect and destroy, as well as deliver cargo, to MUC1 expressing tumors. (Supported by NIH grants HD29963 to DDC, and MD Anderson Gynecologic SPORE for Uterine Cancers 2 P50 CA098258-06 to DDC and RB). 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 368. doi:10.1158/1538-7445.AM2011-368
Abstract 5458: Individual and combined activities of STAT1 and STAT3 have prognostic relevance for the progression of colorectal carcinoma.
Authors: Claire Gordziel, Harini Nivarthi, Thomas Knösel, Helmut Dolznig, Richard Moriggl, Karlheinz Friedrich
Journal: Cancer Research (2013)

Abstract Aberrant activities of JAK/STAT signalling pathways have been implicated in the development and spread of various cancer entities, among them colorectal carcinoma (CRC). By immunohistochemical analysis of a tissue microarray covering more than 400 CRC biopsies from patients with full clinical documentation, the expression and activity status of STAT1 and STAT3 was determined. Results were correlated with clinical information. A significant association of high STAT1 activity (as indicated by nuclear location) with longer patient overall survival was observed. Unexpectedly, strong STAT3 expression in surgical specimens could be clearly correlated with an increase in median overall survival by about 30 months. Interestingly, combined consideration of STAT1/3 expression and activity levels in CRC specimens revealed patterns that match the clinical outcome with statistical significance. For instance, tumors with concomitant absence of STAT1 and STAT3 have a worse prognosis, while high STAT1 activity along with low STAT3 activity proved associated with longer patient survival. To address the signal transduction background of these findings, STAT1/3 expression was experimentally modified in CRC cell lines and effects on the growth of xenograft tumors were studied. Mimicking STAT1/3 patterns from patient biopsies in xenografts resulted in alterations in tumor growth well corresponding to clinical data. From these experiments we draw the conclusions that the ratio of nuclear STAT1/STAT3 is a determinant of colon carcinoma progression. Supported by: Deutsche Krebshilfe, IZKF Jena, European Regional Development Fund ERDF Citation Format: Claire Gordziel, Harini Nivarthi, Thomas Knösel, Helmut Dolznig, Richard Moriggl, Karlheinz Friedrich. Individual and combined activities of STAT1 and STAT3 have prognostic relevance for the progression of colorectal carcinoma. [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 5458. doi:10.1158/1538-7445.AM2013-5458
Abstract 2759: Targeting NF2 deficient meningiomas with combinations of small molecule inhibitors and radiation
Authors: Gilson S. Baia, Graeme Woodworth, Eric Ford, Gregory Riggins
Journal: Cancer Research (2012)

Abstract Meningiomas are common tumors of the central nervous system and are the second most prevalent tumors in Neurofibromatosis type 2 patients. Despite their high frequency, currently there are no chemotherapeutic options for these tumors and treatment is limited to surgery and various forms of radiation therapy either as adjuvant or primary therapy. Some tumors are unresectable due to location and have histhopathologic aggressive features (designated as WHO grade II and III) with higher recurrence rates. When treatment is recommended, these tumors almost uniformly receive some form of radiation therapy. The aim of this study was to find new therapeutic options to couple with radiation, given its common use with non-surgical meningiomas. We are interested in targeting oncogenic pathways in the context of loss of the NF2 gene, which represents the most common genetic alteration in meningiomas, present is 50-70% of sporadic tumors and all of NF2 cases. We used cell-based assays searching for small molecule inhibitors that showed prevalent efficacy against NF2-deficient cells. Cell proliferation and clonogenic assays were employed to investigate the potential synergy effect of drugs and radiation combinations. Three pairs of NF2 isogenic meningioma cells (AC1, SF6717 and KT21MG1) were used to screen libraries of FDA approved compounds. The primary screen was performed using KT21MG1 cells. The top 5% compounds (86 compounds) showing preferential inhibition of NF2-deficient cells were selected for further validation. The secondary screen was used to validate useful targets with AC1 and SF6717 cells. Twelve compounds (∼15%) showed prevalent inhibitory activity on these cells. Small molecules targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor receptor (VEGFR) showed preferential synergistic inhibition of NF2 cells with radiation, compared to either radiation or drug treatment alone. Currently, preclinical testing is in progress to investigate the efficacy of these inhibitors in combination with radiation in a meningioma mouse model. 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 2759. doi:1538-7445.AM2012-2759
Tumor Necrosis Factor and Disease Severity in Children with Falciparum Malaria
Authors: Georges E. Grau, Terrie E. Taylor, Malcolm E. Molyneux, Jack J. Wirima, Pierre Vassalli, Marcel Hommel, Paul-Henri Lambert
Journal: New England Journal of Medicine (1989)

To investigate the role of tumor necrosis factor in Plasmodium falciparum infections, we measured serum concentrations of this cytokine in 65 Malawian children with severe falciparum malaria. Of these children (mean age, 5.3 years), 55 were unconscious and 10 had hypoglycemia at presentation. Although there was considerable overlap, the mean (±SEM) initial serum concentration of tumor necrosis factor was significantly higher in the 10 patients who died (709±312 pg per milliliter) than in the 55 who survived (184±32 pg per milliliter; P<0.02). The mortality rate increased with the concentration of tumor necrosis factor: at a level of less than 100 pg per milliliter, 1 of 24 patients died; at 100 to 500 pg per milliliter, 6 of 34 patients; and at more than 500 pg per milliliter, 3 of 7 patients. High concentrations of tumor necrosis factor were also associated with hypoglycemia (P<0.02), hyperparasitemia (P<0.002), age under three years (P<0.03), and severity of illness as measured by a prognostic index (P<0.0005). The highest serum concentrations of tumor necrosis factor were found in patients who died shortly after admission. The concentrations in cerebrospinal fluid were within the normal range in all patients. In serum samples obtained from 38 convalescent patients, the concentration of tumor necrosis factor declined to a mean of 16±3 pg per milliliter. We conclude that the level of tumor necrosis factor is frequently increased in patients with severe falciparum malaria, particularly in those with cerebral malaria or hypoglycemia. To determine whether it is important in the pathogenesis of the signs and symptoms of the disease requires further study. (N Engl J Med 1989; 320:1586–91.)
Margaret McCartney: Stop disciplining us for being ill
Authors: Margaret McCartney
Journal: BMJ (2016)

Doctors, unsurprisingly, get sick. The UK General Medical Council says, “If you have a health condition or have a problem with alcohol or drugs that may put patients at risk, you need to let us know so that we can ensure that patients are protected.”1

One doctor told me that she’d told the GMC that she thought she could put patients at risk if she had a relapse of her chronic mental illness. This led to a fitness to practise process, even though she’d taken independent advice, spent time off work as advised, …
Carcinosarcoma of the Uterine Corpus on 18F-FDG PET/CT in a Postmenopausal Woman With Elevated AFP
Authors: Feng Chen, Chunjing Yu, Xuyang You, Boming Mi, Weixing Wan
Journal: Clinical Nuclear Medicine (2013)

Uterine carcinosarcoma (termed malignant mixed müllerian tumor) is a rare neoplasm of the uterus with a poor prognosis. There have been very few cases in the literature describing the PET/CT findings of uterine carcinosarcoma. We report a case of tissue-proven carcinosarcoma of the uterine corpus in a 65-year-old woman with elevated serum alpha-fetoprotein (AFP), whose 18F-FDG PET/CT showed a 10.3-cm mass in the uterus with uneven high FDG uptake. The SUVmax was 12.8. After surgery, the patient received 6 courses of chemotherapy, and the serum levels of AFP decreased to reference range.
EFFICACY OF CD34+ STEM CELL THERAPY IN NON-ISCHEMIC DILATED CARDIOMYOPATHY IS ABSENT IN PATIENTS WITH DIABETES BUT PRESERVED IN PATIENTS WITH INSULIN RESISTANCE
Authors: Bojan Vrtovec, Matjaz Sever, Mojca Jensterle, Gregor Poglajen, Andrej Janez, Nika Kravos, Gregor Zemljic, Marko Cukjati, Peter Cernelc, Francois Haddad, Joseph C. Wu, Ulrich P. Jorde
Journal: Journal of the American College of Cardiology (2015)
PWE-018 Evaluation of the Bowel Screening Wales Network Multidisciplinary Team and National Referral Centre Pilot
Authors: R Stiff, H Heard
Journal: Gut (2013)

<h3>Introduction</h3> The Bowel Screening Wales (BSW) Network Multi Disciplinary Team (NMDT) and National Referral Centre (NRC) pilot was established in October 2011 to offer the opportunity for expert opinion and discussion of therapeutic options for participants with complex benign polyps detected on the Welsh bowel screening programme. Formal evaluation of the pilot was undertaken to inform future service development and focused on establishing the views of participants. <h3>Methods</h3> All screening participants with complex benign polyps referred to the NMDT between the 1st of January and the 17th of April 2012 were included in the evaluation. Telephone interviews were conducted by members of BSW staff without direct involvement in their care using a structured questionnaire. Questions were of two different formats: some required responders to choose from a selection of structured options; whilst others required free-flowing text responses. Both qualitative and quantitative analysis methods were used. <h3>Results</h3> A total of 41 screening participants were referred to the NMDT during this time frame. Twenty four participants agreed to take part in the evaluation (59%). Participants who responded were geographically dispersed and had a variety of management outcomes following index screening colonoscopy. The importance participants placed on being involved in decision making about their care was emphasised by nineteen (79%) responders who considered it essential or important that a decision by the local team to refer their case to the NMDT was discussed with them prior to referral. Most responders (92%) reported that following index colonoscopy, management options were discussed with them. Twenty one responders (87%) reported that they had received sufficient information for them to be able to make an informed choice about the best clinical option for them. Although overall awareness of the NMDT and NRC pilot among screening participants was low (only 5 responders- 21% were aware), nine participants (38%) reported they were aware that their local team could seek advice about their clinical management from a group of experts outside of the immediate local team. <b>Participants</b>’ opinion about the overall service they received from the NRC was favourable, with 6 (86%) individuals describing the service as excellent and one individual describing the service as good. <h3>Conclusion</h3> The BSW NMDT and NRC pilot was established to facilitate informed choice and to develop an equitable service for participants of the bowel screening programme in Wales. Evaluation of the initial pilot stage confirmed that participants felt involved in decision making about their treatment options and that the service was received positively. Initial evaluation would suggest that the pilot met the aim of developing an equitable participant focused service. <h3>Disclosure of Interest</h3> None Declared.
Abstract 329: Downregulation of PKC∈/par3/par6 polarity complex is critical for hypoxia-induced epithelial-mesenchymal transition, migration, and invasion in lung cancer cells
Authors: Qiyuan Zhou, Tianji Chen, Joyce Christina F. Ibe, J. Usha Raj, Guofei Zhou
Journal: Cancer Research (2012)

Abstract Rationale: We have previously reported that hypoxia induces epithelial-mesenchymal transition (EMT) in lung cancer cells. EMT has been known to contribute to tumor cell invasion and metastasis. Recent evidence suggests that loss of cell polarity complex, which consists of atypical protein kinase C ≤ (PKC∈), Par (partitioning defective) 3, and Par6, is strongly correlated with malignancy. However, it is unknown whether hypoxia-induced cancer cell migration, invasion, and metastasis are caused by the loss of PKC∈/Par3/Par6 polarity complex and subsequent EMT. Methods: We incubated A549 in hypoxic conditions (1.5% O2) for a period of time and assessed the protein abundance of α-SMA, vimentin, E-cadherin, PKC∈, Par3, and Par6 as well as PKC∈ ubiquitination. Next we knocked down PKC∈/Par3/Par6 by siRNAs and determined the abundance of α-SMA, vimentin, and E-cadherin. We also measured cell migration and invasion after knockdown of PKC∈/Par3/Par6 in vitro. In addition, we established A549 cells with knockdown of Par3 and determined cell proliferation rate and lung colonization in a mouse tail-vein injection model, in which lung cancer cells were injected intravenously into the tail vein of mice and lung metastatic foci were quantified in five weeks. Furthermore, we obtained human lung adenocarcinoma tissue samples and self-matched adjacent normal tissues as well as unmatched normal tissues and detected the expression levels of PKC∈/Par3/Par6 polarity complex. Results: We found that A549 cells exposed to hypoxia expressed decreased PKC∈/Par3/Par6 polarity complex and E-cadherin and increased expression of α-SMA and vimentin, suggesting that loss of PKC∈/Par3/Par6 polarity complex is associated with the induction of EMT. We also showed that hypoxia increased ubiquitination of PKC∈. Our results also showed that loss of either of PKC∈, Par3, or Par6 resulted in EMT, elevated migration and invasion, and increased the numbers of metastatic foci in the lungs. Moreover, we show that human lung adenocarcinoma tissues express less Par6 protein than the adjacent normal tissues. Conclusions: These results suggest that in lung cancer cells hypoxia downregulates PKC∈/Par3/par6, leading to EMT and increased cancer cell migration, invasion, and colonization. Support: UIC Faculty Scholarship Support Program and the University of Illinois Cancer Center Pilot Subsidy Program. 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 329. doi:1538-7445.AM2012-329
Abstract 282: FGF receptor signaling accelerates Wnt-1 mammary tumorigenesis and enhances translation of Wnt/β-catenin target oncogenes
Authors: Adam C. Pond, Jason I. Herschkowitz, Susan Hilsenbeck, Chad Creighton, Richard E. Lloyd, Jeffrey M. Rosen
Journal: Cancer Research (2010)

Abstract The fibroblast growth factor pathway is known to cooperate with the Wnt/B-catenin pathway in mouse mammary tumorigenesis, and both of these pathways have been implicated in the etiology of human breast cancer. Despite this evidence, little is known about the molecular mechanism contributing to FGF/Wnt pathway cooperation. To investigate the mechanisms involved in this cooperativity, we used genetically engineered mice expressing a drug-inducible model for FGF Receptor signaling (iFGFR) crossed with the well-characterized MMTV-Wnt-1 mouse model. In these bigenic mice, iFGFR1 activation resulted in a dramatic enhancement of mammary tumorigenesis. Tumor microarray analysis did not reveal transcriptional enhancement of Wnt/B-catenin targets, but instead identified a protein translational gene signature that also correlated with elevated FGFR1 and FGFR2 expression in several human breast cancer data sets. Additionally, iFGFR1 activation resulted in enhanced polysome recruitment and a marked increase in protein expression of several different Wnt/B-catenin target oncogenes. Rapid FGFR1-induced ERK activation and phosphorylation of key translation regulators was observed both in vivo in the transgenic mouse model, and in a human breast cancer cell line treated with exogenous FGF. These studies suggest that translational regulation is a key rate-limiting step required for oncogenic cooperativity between the Wnt and FGF pathways. These results not only demonstrate the oncogenic potential of FGFR1 signaling, but also highlight a possible mode of cooperation between FGF and Wnt signaling, involving synergism between two fundamental levels of gene regulation, transcription and translation. FGFRs, provide drugable targets for adjuvant therapy and several known FGFR inhibitors are currently in clinical trials. Additionally, key downstream regulators of translation initiation may also serve as potential therapeutic targets for breast cancers with enhanced FGF signaling. 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 282.
Endoscopic closure of a rectovaginal fistula combining<i>N</i>-2-butyl-cyanoacrylate (Histoacryl) and Resolution clips
Authors: C. Ortiz-Moyano, P. Guerrero-Jiménez, M. Romero-Gómez
Journal: Endoscopy (2011)

Rectovaginal fistulas (RVFs) are abnormal communications between the anterior wall of the rectum and the posterior vaginal wall. The incidence of RVFs is relatively low; most of them are related to obstetric injury [1]. Patients complain of uncontrollable passage of gas or feces from the vagina. RVFs may be managed both medically and surgically. Endoscopic approaches with endoclip closure of gastrointestinal fistula and injection of tissue adhesive have been proposed [2], but a combined approach using both methods has not been described. We present a case of a RVF successfully treated endoscopically with N-2-butyl-cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and Resolution clips (Microvasive Endoscopy, Boston Scientific Corp., Natick, Massachusetts, USA).
Changing our perspective in endoscopic ultrasound (EUS) and ERCP
Authors: Benedetto Mangiavillano, Todd Baron
Journal: Endoscopy (2015)

In the last 20 years, we have observed a continuous evolution in endoscopic ultrasound (EUS) as the quality of images has markedly improved, an increasing number of endoscopists have performed the technique, and it has transitioned from a technique purely for diagnostic imaging [1] to an invasive diagnostic procedure with the advent of fine needle aspiration (FNA) [2] and, finally, to a therapeutic procedure. Therapeutic options now include EUS-guided cystgastrostomy, hepaticogastrostomy, and choledochoduodenostomy [3].
Abstract 5372: Mechanisms of synergy of histone deacetylase inhibitors, belinostat and depsipeptide, with DNA damaging agents, etoposide and cisplatin in small cell lung cancer cell lines
Authors: Victoria Luchenko, Crystal D. Salcido, Yongwei W. Zhang, Melanie D. Mumau, Kelli Agama, Giuseppe Giaccone, Yves Pommier, Susan E. Bates, Lyuba Varticovski
Journal: Cancer Research (2010)

Abstract Small cell lung cancer (SCLC) is the most aggressive type of lung carcinoma. SCLC has a high response rate to chemotherapy, but rapid onset of drug resistance. Chemotherapeutic treatment using combinations of drugs that target different signaling pathways improves overall survival of patients with SCLC. Histone deacetylase (HDAC) inhibitors regulate epigenetic changes and play a role in regulating cell cycle progression and have been suggested as potential therapeutic agents for SCLC. HDAC inhibition is thought to relax DNA, thereby allowing increased access of transcription factors to certain promoters. Likewise, they could increase accessibility of DNA to cytotoxic agents. We examined whether two distinct HDAC inhibitors, belinostat and depsipeptide, have an effect on SCLC cell lines and whether they could be combined with conventional agents used for SCLC, VP16 (etoposide) and cisplatin. We used simultaneous and schedule-dependent treatment protocols of SCLC cells with single drugs and drug combinations. Computational analysis of cell survival using combination index (CI) showed that HDAC inhibitors synergized with DNA damaging agents when administered simultaneously, but this effect was only additive if cells were pre-treated with HDAC inhibitors for 24 hours prior to DNA damaging agents. In addition, using DNA damaging agents 24 hours prior to HDAC inhibitors was clearly antagonistic with CI &amp;gt;1 for all drugs and cell lines tested. Because of a potential use of belinostat and depsipeptide for therapy of SCLC in combination with conventional chemotherapies, we examined the mechanisms of synergy and protection between these agents. We found that PARP degradation was complete when drugs were used simultaneously, but was decreased if HDAC inhibitors were used prior to cisplatin or etoposide. Similar effects were observed by analysis of cell cycle and γH2AX phosphorylation. Thus, schedule of drug administration will be critical for development of clinical protocols for therapy of SCLC using these agents. 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 5372.