tbuckley/cabot-search huggingface dataset:
Abstract 5366: Chronic, low-dose treatment with sulforaphane inhibits growth of breast cells.
Authors: Ashley L. Silvia, Eva P. Browne, Kathleen F. Arcaro
Journal: Cancer Research (2013)

Abstract Epidemiological data indicate that dietary consumption of cruciferous vegetables may reduce the risk of many cancers including breast cancer. Cruciferous vegetables contain high levels of glucosinolates; stable phytochemicals that when metabolized produce cancer-preventing active isothiocyanates. Isothiocyanates, such as sulforaphane (SFN) found in broccoli sprouts, are thought to prevent tumorigenesis through epigenetic mechanisms controlling the expression of tumor-related genes. Ingestion of broccoli sprouts results in rapid distribution of SFN to breast epithelium, however, the effect of chronic exposure to low levels of SFN on the growth of breast cells has not been fully explored. In the present study we assessed the effect of SFN on the growth of an immortalized breast cell line (MCF10A), and two breast cancer cell lines; the estrogen receptor positive MCF-7 cell line, and the estrogen receptor negative TMX2-28 cell line. We first determined the seeding densities for each cell line that resulted in 80% confluence after three days of growth in T-25 flasks: MCF10A (1 x 106), MCF-7 (8 x 105), and TMX2-28 (5 x 105) per 5 mL. Next, cells from each line were plated at the predetermined seeding densities in T-25 flasks and treated with either SFN (5 μM) or vehicle (0.02% DMSO) for up to 40 days. Every third day, cell cultures were photographed, after which the cells were resuspended in culture medium, counted using a hemocytometer, and the predetermined numbers of cells (seeding numbers) were returned to T-25 flasks and treated with SFN or vehicle. Cells not needed for seeding the flasks were archived for future analysis of gene expression and DNA methylation. Treatment with SFN decreased cell growth. After 22 days of treatment with SFN, mean proliferation of both the MCF10A and MCF-7 cell cultures was inhibited by 62% (t = 2.8; p = 0.02) and 72% (t = 2.6; p = 0.02), respectively. In contrast, the decrease in proliferation of TMX2-28 cells treated with SFN was not statistically significant (t = 1.2; p = 0.255) from the vehicle control at 22 days. However, by day 40, TMX2-28 cell cultures treated with SFN showed a significant decrease in mean proliferation 36% (t = 2.2; p = 0.04). Ongoing studies are examining the epigenetic mechanisms by which SFN decreased cell proliferation. Citation Format: Ashley L. Silvia, Eva P. Browne, Kathleen F. Arcaro. Chronic, low-dose treatment with sulforaphane inhibits growth of breast cells. [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 5366. doi:10.1158/1538-7445.AM2013-5366
PTU-015 Trainee Endoscopic Procedures by Deanery and Year of Training in the United Kingdom: August 2011 to July 2012. are we doing Enough?
Authors: T Ambrose, P Dunckley, A Ellis
Journal: Gut (2013)

<h3>Introduction</h3> The burden of acute medicine on specialty trainee registrars (StR) is rising. Anecdotal evidence suggests that fewer endoscopic procedures are being performed by gastroenterology (GI) StR’s and that trainees although competent at the time of being awarded their CCT may have less confidence in their endoscopic skills when compared to a historical cohort. The annual review of competency progression (ARCP) decision aid includes indicative numbers of procedures which should be undertaken annually. Since September 2010 all endoscopic procedures undertaken by UK GI trainees have been recorded on a national electronic record (the Joint Advisory Group Endoscopy Training System (JETS)). <h3>Methods</h3> We obtained anonymised records from the JETS database for the period 3 August 2011 – 31 July 2012. We analysed the data by trainee grade (ST3–7, locum appointment for training (LAT’s)), deanery, numbers and type of procedure, and annual numbers of endoscopy lists (dedicated training, ad-hoc training, and service). Duplicate entries &amp; blank entries were removed. <h3>Results</h3> A total of 721 records were obtained from the 19 UK deaneries. 183 blank records were deleted leaving 538 for analysis. 49 (9.1%) were ST3 trainees, 101 (18.8%) ST4, 142 (26.4%) ST5, 120 (22.3%) ST6, 102 (18.9%) ST7, and 24 (4.5%) LAT. Significant variation was seen between trainees both within individual deaneries and between deaneries. The median exposure to endoscopic units (OGD/flexi = 1 unit; colon = 2 units) increased from ST3-ST6 (112–218–275–304) before tailing off at ST7 (227). LAT trainees performed fewer endoscopic units (median 97 units). This pattern was also seen for median number of procedures. Numbers of colonoscopies were generally low across all deaneries. 8 deaneries outperformed the ARCP targets for overall procedures performed at ST3 level and this was accounted for largely by OGDs. Few deaneries met the published targets at ST4-ST7 level. Trainees performed an average of 31 training lists each year (range 0–134; median 29) and 12 service lists (range 0–210) the latter of which were largely, but not entirely, restricted to senior trainees in this dataset. <h3>Conclusion</h3> Trainees are performing fewer procedures than recommended in the ARCP guidelines. The variation in endoscopy numbers both between and within trainee grade and deanery suggest factors which can be explored to optimise future opportunities. This analysis should be undertaken regularly to inform The Training Committee of future trends in endoscopic training. <h3>Disclosure of Interest</h3> None Declared
Tc-99m HMPAO-Labeled WBC Scans to Detect Appendicitis in Women
Authors: C. H. KAO, H. T. LIN, Y. L. WANG, S. J. WANG, T. J. LIU
Journal: Clinical Nuclear Medicine (1996)

Fifty female patients with acute abdomen and suspected appendicitis but atypical findings were included in this study. After intravenous injection of Tc-99m HMPAO-labeled WBCs, serial anterior abdominal/pelvic images at 30, 60, 120, and 240 minutes were obtained by a gamma camera. Any abnormal localization of WBC accumulation in the right lower quadrant of the abdomen with equal to or greater than bone marrow activity was considered as a positive scan. Thirty patients had positive WBC scans and underwent laparotomy, 28 had proven appendicitis, and 2 were not related to appendicitis. Twenty patients had negative WBC scans, 2 patients underwent laparotomy and were proved to have appendicitis. The remaining 18 patients did not undergo surgery and revealed no evidence of appendicitis after follow-up. The overall sensitivity, specificity, accuracy, and positive and negative predictive values for WBC scans to diagnose appendicitis is 93.3%, 90.0%, 92.0%, 93.3%, and 90.0%, respectively. In conclusion, Tc-99m HMPAO-labeled WBC imaging provides a rapid and highly accurate method for diagnosis of appendicitis in female patients with equivocal clinical examinations.
Synovial fluid mononuclear cells provide an environment for long-term survival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies
Authors: Priscilla F Kerkman, Ayla C Kempers, Ellen I H van der Voort, Maikel van Oosterhout, Tom W J Huizinga, René E M Toes, Hans U Scherer
Journal: Annals of the Rheumatic Diseases (2016)

Objectives In rheumatoid arthritis (RA), observations point to a crucial role for (autoreactive) B cells in disease pathogenesis. Here, we studied whether cells from the synovial environment impact on the longevity of autoreactive B cell responses against citrullinated antigens. Methods Synovial fluid mononuclear cells and peripheral blood mononuclear cells (SFMC/PBMC) were obtained from patients with established RA and assessed for the presence of B cell subpopulations. Cells spontaneously secreting anti-citrullinated protein antibodies (ACPA-IgG) directly ex vivo were detected by antigen-specific Enzyme-Linked ImmunoSpot (ELISpot) assay. SFMC and PBMC were cultured to assess the degree of spontaneous ACPA-IgG secretion. Cells surviving for several weeks were characterised by carboxyfluorescein succinimidyl ester (CFSE) labelling and Ki-67 staining. Results Cells spontaneously secreting ACPA-IgG were readily detectable in peripheral blood and synovial fluid (SF) of patients with ACPA-positive RA. SFMC showed an up to 200-fold increase in ex vivo ACPA-IgG secretion compared with PBMC despite lower numbers of B cells in SFMC. ELISpot confirmed the presence of spontaneously ACPA-IgG-secreting cells, accounting for up to 50% (median 12%) of all IgG-secreting cells in SF. ACPA-IgG secretion was remarkably stable in SFMC cultures, maintained upon depletion of the CD20 + B cell compartment and detectable for several months. CFSE labelling and Ki-67 staining confirmed the long-term survival of non-dividing plasma cells (PCs). Conclusions This study demonstrates a high frequency of differentiated, spontaneously ACPA-IgG-secreting cells in SF. These cells are supported by SFMC for prolonged survival and autoantibody secretion, demonstrating that the synovial compartment is equipped to function as inflammatory niche for PC survival.
Immunotrans-Arterial Chemoembolization (ITACE) in Hepatocellular Carcinoma Patients Treated with anti-EGFR Mab Nimotuzumab Plus Adriamycin. Phase I Clinical Trial, Final Results
Authors: Mayra Ramos-Suzarte, Julio Cesar Perera, Alejandro Valdez, Jose Carlos Ugarte Suarez, Jose Jordan, Marcia Samada Suarez, Patricia Lorenzo Luaces, Aymara Fernandez Lorente, Mauricio Catala Ferrer, Eduardo Fermin Hernandez, Aliuska Frias, Mabel Alvarez, Mercedes Cedeño, Enrique Rengifo, Milagros Frometa, Tania Crombet Ramos
Journal: Annals of Oncology (2013)
S116 Parasternal muscle electromyelography (EMGpara) reflects observed changes in dynamic hyperinflation during acute exacerbations of chronic obstructive pulmonary disease (AECOPD)
Authors: E. Suh, M. Ramsay, S. Mandal, E. Boleat, B. Christian, K. Henderson, P. Murphy, J. Moxham, N. Hart
Journal: Thorax (2011)

<h3>Background</h3> During AECOPD, expiratory flow limitation results in dynamic hyperinflation (DH), respiratory neuromechanical uncoupling, and increased work of breathing causing breathlessness. We have previously demonstrated that 2nd intercostal space EMG<sub>para</sub>, as a direct marker of neural respiratory drive (NRD), is able to detect clinical change in hospitalised AECOPD patients. We hypothesised that EMG<sub>para</sub> has an indirect relationship with DH. <h3>Method</h3> Patients admitted with AECOPD at a metropolitan teaching hospital were recruited. Inspiratory capacity (IC) was used as a measure of DH. EMG<sub>para</sub>, spirometry and IC manoeuvres were measured twice daily from admission until the patient was fit for discharge. Dyspnoea scores (modified Borg score, visual analogue scale and numerical rating scale) were recorded. NRD was expressed as EMG<sub>para%max</sub>: inspiratory EMG<sub>para</sub> signal normalised to a maximum signal measured during a sniff manoeuvre. The changes in EMG<sub>para%max</sub> (?EMG<sub>para%max</sub>) and IC (ΔIC) between admission and discharge were analysed. <h3>Results</h3> 31 patients were recruited; only 20 (65%) were able to perform spirometry and IC manoeuvres. The baseline characteristics were 69±11 years; male 55%; body mass index 26.1±7.3 kg/m<sup>2</sup>; %predicted FEV<sub>1</sub> 36.3±9.3; and 41±24 smoking pack years. The overall mean ΔEMG<sub>para%max</sub> of the 20 patients fell by 4%, with 16 (80%) patients experiencing a fall in EMG<sub>para%max</sub> during their admission. We observed an indirect relationship between ΔEMG<sub>para%max</sub> and ΔIC (r=−0.52, p=0.02), and between ΔEMG<sub>para%max</sub> and ΔFVC (r=−0.585, p=0.036). We found a correlation between ΔIC and ΔFEV<sub>1</sub> (r=0.658, p=0.015). There were differences in ΔIC between patients whose EMG<sub>para%max</sub> decreased during their admission and those whose EMG<sub>para%max</sub> increased (mean difference 0.50 l; p=0.003) (Abstract S116 figure 1). There were no significant correlations between dyspnoea scores and ΔIC or ΔEMG<sub>para%max</sub>. <h3>Conclusion</h3> DH is a significant contributor to NRD in AECOPD. ΔEMG<sub>para%max</sub> reflects changes in DH during hospital admission, but patient-reported dyspnoea does not indicate the degree of DH, highlighting the limitations of dyspnoea scores. Changes in DH are correlated with changes in airflow obstruction. These data provide a physiological rationale for the utility of parasternal EMG as a non-invasive and non-volitional technique to track clinical change in AECOPD patients.
Abstract 1731: Decreased cyclin B1 expression contributes to mitochondrial apoptosis in medulloblastoma.
Authors: Venkata Ramesh Dasari, Swapna Asuthkar, Arun Kumar Nalla, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Medulloblastoma, the most common malignant pediatric brain tumor, remains difficult to cure. Previously, we have shown that downregulation of MMP-9 and uPAR induces Chk1-mediated G2/M cell-cycle arrest in medulloblastoma cells. In this study, we observed that downregulation of MMP-9 in nude mice D283 xenografts downregulated the expression of cyclin B1. Increasing evidence indicates that the deregulation of cyclin B1 is involved in neoplastic transformation, suggesting that inhibition of cyclin B1 could be an attractive strategy for anti-tumor therapy. To determine the effect of downregulation of cyclin B1, we treated medulloblastoma cells with nocodazole, which is an anti-neoplastic agent. Nocodazole-treated cells have undergone G2/M cell-cycle arrest because of the mitotic spindle arrest. Prolonged arrest of cells in mitosis due to nocodazole treatment typically results in cell death by apoptosis. Hence, we confirmed the induction of apoptosis in medulloblastoma cells by TUNEL analysis. Immunoblot analysis of cell cycle checkpoint proteins Chk1, Chk2 and cyclin B1 revealed that they were downregulated in combination treatments of shMMP-9 with radiation. Further, apoptotic proteins BAD, BAX and BAK were highly upregulated, which shows the involvement of mitochondria-mediated apoptosis in our treatments. In vivo analysis of BAD molecules in D283 nude mice xenografts confirmed that downregulation of cyclin B1 induces BAD-mediated apoptotic death in medulloblastoma tumors treated with either shMMP-9 alone or in combination with radiation. With this study, we demonstrate that downregulation of cyclin B1 is an effective and specific approach to induce apoptosis for effective anti-tumor therapy against medulloblastoma. Citation Format: Venkata Ramesh Dasari, Swapna Asuthkar, Arun Kumar Nalla, Jasti S. Rao. Decreased cyclin B1 expression contributes to mitochondrial apoptosis in medulloblastoma. [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 1731. doi:10.1158/1538-7445.AM2013-1731
Abstract LB-27: Systematic identification of genes contained the translational regulation element IRES in the cancer development
Authors: Joseph Ta-Chien Tseng
Journal: Cancer Research (2010)

Abstract Internal Ribosome Entry Site (IRES) is a cis-acting element located at the 5′ untranslated region to regulate the protein translation. Translation by internal ribosome entry was first identified in picornaviruses, but a number of cellular mRNAs containing IRESs have subsequently been found, including basic fibroblast growth factor, c-myc, p53, and HIF-1. Till now, around 80 cellular IRES elements have been identified, almost half found in genes encoding oncogenes, growth factors, and proteins involved in the regulation of apoptosis. This suggests that IRES-dependent translation is an important regulatory mechanism for the maintenance of cellular homeostasis, especially when cap-dependent initiation is inhibited. Therefore, it would be interested to understand how many genes bearing the IRES to elucidate the functional role of IRES. In this study, the pattern search algorithm was used to screen the whole human transcripts to identify the genes bearing the IRES elements. A special phenomenon which multiple IRES structures existed in specific region was found, and this region was named as internal ribosome entry zone (IREZone). The total human transcripts were identified to contain the IRES or IREZone element about 24.8% and 45.6%, respectively. By using bicistronic assay, the activity of IRES zone is higher then the single IRES existed in the 5′UTR of c-jun. Via Ingenuity software, we found that the cancer-related genes carry multiple IRES or IREZone in their 5′UTR. This result indicated these cancer-related genes are more tightly regulated at translational level to express the protein in the right time. And the mis-regulation of these proteins expression may lead to the cancer development. 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 LB-27.
VALUE OF NEUTROPHIL TO LYMPHOCYTE RATIO AS A PREDICTOR OF MORTALITY IN PATIENTS UNDERGOING AORTIC VALVE REPLACEMENT
Authors: Mirette Habib, Mohammad Thawabi, Amer Hawatmeh, Habib Habib, Walid ElKhalili, Fayez Shamoon, Medhat Zaher
Journal: Journal of the American College of Cardiology (2015)
Abstract 1895: The role of autophagy and Atg3 in erlotinib-resistant lung cancer and synergistic cell death with combination of erlotinib and cisplatin
Authors: Jasmine G. Lee, Reen Wu
Journal: Cancer Research (2012)

Abstract Objective: Erlotinib is a mainstay anti-cancer agent for non-small-cell lung cancer (NSCLC) but resistance to erlotinib is a major problem, clinically. The combination of cisplatin and erlotinib has been suggested to inhibit tumor growth more effectively than a single drug alone in sensitive NSCLC. However, the mechanism underlying this finding remains unclear. The specific role of autophagy in cancer and chemotherapy resistance continues to be unclear (promotion vs. prevention of cancer). In this study, we investigate whether combination low dose erlotinib and cisplatin is effective against erlotinib resistant NSCLC and examined the role of autophagy in erlotinib resistance. Methods: PC9, a NSCLC cell line, was used to develop erlotinib resistant PC9 cells (PC9ER). Cell survival was quantified with Alamar blue assay. LC3II and regulatory proteins of autophagy were measured by western blot. Small interfering RNA (siRNA) transfection was used to block translation of protein of interest. Results: Combination low dose erlotinib and cisplatin resulted in synergistic cell death in PC9ER cells (p&amp;lt;0.0001) and a significant decrease in autophagy (p=0.011). At baseline, there was a significantly higher level of LC3II in PC9ER cells compared to sensitive PC9 (p=0.030) suggesting autophagy may play a role in resistance. Rapamycin significantly increased ER (p=0.0004) and 3-MA significantly sensitized PC9ER cells to treatment (p=0.037). Upon examination of autophagy regulatory proteins between PC9ER and PC9 cells, there was significantly lower levels in p-mTOR (p=0.021) and higher levels of Atg3 in PC9ER at baseline (p=0.018). Among the four treatment groups (control, erlotinib-alone, cisplatin-alone, and erlotinib-cisplatin combination), there was a specific decrease in Atg3 with combination treatment (p=0.005). siRNA transfection of Atg3 resulted in the reversal of ER: 42% more cell death with erlotinib-alone (p&amp;lt;0.0001), 18% more cell death (p=0.002) in cisplatin treatment, and 9% more cell death in erlotinib-cisplatin combination (p=0.047) compared to the counterpart treatment groups without siRNA transfection. Conclusions: Our data may suggest that autophagy may promote cancer survival and ER in NSCLC, specifically by up regulation of Atg3 and targeting of Atg3 may be the key to re-sensitizing erlotinib resistant cancers. In addition, it seems erlotinib-cisplatin combination is an effective therapy by down modulation of autophagy by targeting Atg3. Future pharmacologic therapies specifically targeting Atg3 in complement to erlotinib therapy may be effective in preventing and treating ER. 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 1895. doi:1538-7445.AM2012-1895
Abstract 2148: Exploitation of androgen receptor splice variant signaling by guanine nucleotide exchange factor Vav3 in castration resistant prostate cancer
Authors: Stephanie Peacock, Cale Fahrenholtz, Kerry L. Burnstein
Journal: Cancer Research (2012)

Abstract The treatment for advanced or metastatic prostate cancer is androgen deprivation therapy. Patients inevitably relapse and the cancer is now termed androgen-independent or castration resistant (CRPC). CRPC remains dependent on androgen receptor (AR) signaling. One of the proteins implicated in the reactivation of AR transcriptional activity in CRPC is Vav3, a Rho GTPase guanine nucleotide exchange factor. Vav3 is up-regulated in human prostate cancer tumors compared to benign tissue and in preclinical models of prostate cancer progression to CRPC. Vav3 enhances AR activity at both physiological and as well as at subnanomolar androgen concentrations, similar to prostatic microenvironment levels demonstrated in CRPC. Vav3 confers castration resistant growth to a classically androgen dependent cell line in a mouse xenograft model. Thus, elevated levels of Vav3 seem to be pivotal in promoting continued AR signaling in CRPC. We examined the contributions of Vav3 to AR activity and cell proliferation in the CRPC cell lines CWR-22Rv1 and CWR-R1. Knockdown of Vav3 attenuated cell growth and reduced AR activity as compared to the shGFP control. However knockdown of full length AR had little effect, perhaps due to impaired ligand-mediated transcriptional activity of the mutated AR expressed in these cell lines. Because CWR-22Rv1 also express AR splice variants that lack the ligand binding domain and are proposed to underlie CRPC growth, we examined the possibility that Vav3 enhances AR splice variant signaling. The AR splice variant, ARV7 (also known as AR3), exhibits constitutive ligand independent activity and is linked to poor prognosis and survival. Depletion of ARV7 in 22Rv1 and CWR-R1 cell lines resulted in slowed growth and lowered AR activity. Soft agar assays revealed that knockdown of either Vav3 or ARV7 resulted in greatly decreased anchorage independent growth. Vav3 potently enhanced the activity of ARV7 in reporter gene assays. Further, knockdown of Vav3 resulted in lowered levels of nuclear AR splice variants in CWR-22Rv1. Co-immunoprecipitation revealed that ARV7 and Vav3 directly interact. These results suggest that Vav3 may enhance ARV7 activity through increased nuclear localization and that the interaction of Vav3 and ARV7 may be required for robust growth of CRPC cells. These novel data demonstrating interaction between a versatile AR coactivator and an AR splice variant provide insights into the possible mechanisms by which Vav3 exploits and enhances AR splice variant signaling in the progression of prostate cancer malignancy and castration resistance. 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 2148. doi:1538-7445.AM2012-2148
Researchers to Comb Long Island for Potential Cancer Factors
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Researchers to Comb Long Island for Potential Cancer Factors Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 88–89, https://doi.org/10.1093/jnci/86.2.88 Published: 19 January 1994