tbuckley/cabot-search huggingface dataset:
Abstract 3108: Exploring base excision repair variants as potential defining events in cancer patient populations and characterization of models for pre-clinical studies
Authors: Lucy C. Riches, Helen Brown, Gillian Dalgliesh, Lynn Fletcher, James Sherwood, Kerry Shea, Alan Lau, Mark J. O'Connor
Journal: Cancer Research (2012)

Abstract Background Deficiencies in base excision repair (BER) may increase the cell's dependence on alternative repair pathways and so define a patient population for novel inhibitors of DNA damage repair. Notably, cancer associated molecular events in DNA polymerase beta (POLα) have been described in various disease backgrounds including colorectal cancer (CRC), gastric, breast and prostate (1-5). Although functional consequence has been linked to certain POLα mutations and splice variants, their prevalence in defined disease segments remains largely undefined. Aim We set out to ascertain the prevalence of POLα deficiencies in CRC, and subsequently investigated protein and gene expression profiling as alternative methods for defining BER defects in cancer. Methods/Results A comprehensive study of clinical (CRC; N=64), tumour explant (CRC; N=36) and cell line (mixed origin; N=280) samples revealed that cancer-associated mutations in the polymerase encoding domain of POLα (1-3) are not common events in CRC. Additionally, a previously described splice variant of POLα lacking part of the polymerase domain (3-4), was assayed and found to be expressed at similar levels in CRC and normal tissue. This would suggest that expression of the POLα splice variant is not a defining element of CRC in western populations. Expression profiling using Fluidigm Taqman revealed a subset of BER genes more highly expressed in CRC clinical samples and mixed cell lines compared with normal tissue. While protein expression profiles did not reflect relative gene expression in selected cell line models, we observed an additional low molecular weight band in a subset of cells profiled for POLB expression. Furthermore, we report variations in the expression of the scaffold protein XRCC1 in colorectal and breast cell lines and propose that this could also provide a mechanism for variation in DNA repair capacity. Summary Although from our studies sequencing and transcript analysis of POLα do not provide suitable markers of BER deficiency in CRC, we report aberrant banding patterns in POLα by Western blotting and variation in XRCC1 protein expression in a subset of cell lines analyzed. We hypothesize that these variants may confer a BER deficient phenotype. 1. Lang, T. et al. (2004Proc. Natl Acad. Sci. USA, 101, 6074-6079. 2. Tan, Xiao-Hui, et al Cancer Letters: 2005: 220: 101-114 3. Wang, L et al Cancer Research, 1992; 52:4824-4827 4. Bhattacharyya, N. et al. (1997) Proc. Natl Acad. Sci. USA, 94, 10324-10329 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 3108. doi:1538-7445.AM2012-3108
Abstract 4052: Analysis of the matrix metalloproteinase family reveals <i>MMP8</i> is often mutated in melanoma
Authors: Xiaomu Wei
Journal: Cancer Research (2010)

Abstract Matrix Metalloproteinases (MMPs) have long been associated with multiple biological processes and a variety of pathological conditions, including cancer because of their ability to degrade extracellular matrices, which facilitates invasion and metastasis. We performed a mutational analysis of the Matrix Metalloproteinase gene family in human melanoma and identified 28 somatic mutations in eight MMPs, affecting 23% of melanomas. Five mutations in one of the most commonly mutated genes, MMP8, reduced MMP-8 enzyme activity. Expression of wild-type but not mutant MMP-8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression. Our findings emphasize the need to test the role of each MMP in an individual manner and to precisely define its functional role in cancer. This may allow the development of individualized therapy based on the mutant MMP present in specific tumors. To extend our knowledge of fundamental roles of proteases in cancer progression, we will compliment the studies by performing a systematic sequence analysis of all ADAMs (A Disintegrin And Metallproteinase) and the related ADAMTS family. Similar to MMPs, ADAM/ADAMTS belong to a super family of zinc-based proteinases, the metzincins. Many members of the ADAM/ADAMTS family have been associated with tumorigenesis and tumor progression. Therefore, our comprehensive genetic studies will provide insight into melanoma pathogenesis. In-depth illustrations of the biochemical and biological effects of the mutated genes will permit the design of personalized treatments for melanoma patients. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4052.
AB0799 Is nailfold videocapillaroscopy a valuable diagnostic tool in pulmonary hypertension?
Authors: F.M. Meier, M. Geyer, H. Tiede, A. Rieth, H.-A. Ghofrani, U. Müller-Ladner, R. Dinser, W. Hermann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, untreated resulting in right ventricular heart failure. PH can be based on idiopathic pulmonary arterial hypertension (iPAH) or associated with connective tissue diseases such as systemic sclerosis (SSc-PAH). PH is also caused by left heart disease (LHD-PH), chronic obstructive pulmonary disease (COPD-PH), or chronic thromboembolic events (CTEPH). <h3>Objectives</h3> In this study analysis of microvascular patterns of microangiopathy of patients with PH have been performed using nailfold videocapillaroscopy (NVC). The benefit of this easy to handle diagnostic tool in PH was evaluated with a distinct focus on SSc patients. <h3>Methods</h3> NVC was performed in 81 patients, of whom 54 had PH due to different disease entities. 27 had systemic sclerosis without PAH. 2nd to 5th fingers were bilaterally analyzed. Three pictures of adequate quality for evaluation, at least one from each hand, were scored for capillary density (CD, capillaries per mm), afferent, efferent, apex and total width. Parameters such as hemorrhages, neoangiogenesis and edema or capillary alterations such as ectasia (&gt;20μm), irregular shape, tortuousity or giant shape (&gt;50μm) were qualitatively assessed. For SSc patients, the respective pattern of microangiopathy (“early”, “active” or “late”) was determined. <h3>Results</h3> 14.8% of the patients had iPAH, 14.8% LHD-PH, 7.4% COPD-PH and 17.2% CTEPH. 45.7% had SSc, of whom 12.3% had SSc-PAH. In SSc, 32% showed the “early” (CD 6.5±1.6), 41% the “active” (CD 4.2±1.2) and 27% the “late” pattern (CD 3.5±0.9). The CD in SSc-PAH was significantly lower compared to all other PH forms (4.9 vs. 10.2, 10.0, 11.7 and 9.47 in iPAH, LHD-PH, COPD-PH and CTEPH; &lt;0.0001), but did not differ compared to SSc non-PAH (4.7; p=0.73). In general, afferent, efferent, apex and total width of capillaries were larger in SSc-PAH. Ectasia was very common in SSc-PAH (90%), but to some extent also present in other forms, most frequently in COPD-PH (71.4%). Giant capillaries were generally only present in SSc (84.6% and 70%). Hemorrhages occurred in all disease forms of this study, however mostly in SSc (80%) and COPD-PH (85.7%). <h3>Conclusions</h3> Assessing capillary density in PH is a powerful tool to discriminate between SSc-PAH and other forms of PH. In this respect, qualitative parameters such as giant shape can support the elucidation of the underlying disease. Besides checking for antinuclear antibodies, NVC should be considered, if the underlying cause of PH is unclear. <h3>Disclosure of Interest</h3> None Declared
GPs in England prescribed 2.7 million extra antidepressants during 2012 recession
Authors: J. Wise
Journal: BMJ (2014)

Antidepressant prescriptions increased significantly in England during the recent recession, and the rise was not based on a corresponding increase in depression in patients, a report from the Nuffield Trust and the Health Foundation has said.1

The research, published as part of the QualityWatch programme, showed a 165% increase in the prescribing of antidepressant drugs in England from 1998 to 2012. Doctors prescribed 15 million items in 1998 compared with 40 million in 2012, the latest year for which data were available. However, the rate of increase has not been stable; the annual rise in prescriptions increased to 8.5% after the banking crash in 2008, compared with 6.7% before it.

The analysis said that the increase was not an artefact …
Abstract 3428: Coordinated regulation of mesenchymal epithelial transition in the PMC42-LA breast cancer cell line variant
Authors: Honor J. Hugo, Bryce JW van Denderen, Eva Tomaskovic-Crook, Tony Blick, Dexing Huang, Cletus Pinto, Eliza Soo, Angels Fabra-Fres, Izhak Haviv, Greg Goodall, Nicholas Wong, Leigh Ackland, Don F. Newgreen, Mark Waltham, Erik W. Thompson
Journal: Cancer Research (2011)

Abstract PMC42 cells were derived from a breast cancer pleural effusion and exhibit stem cell-like features when first characterized (Whitehead, Bertoncello et al. 1983; Whitehead, Monaghan et al. 1983). The PMC42-LA subline (Ackland, Michalczyk et al. 2001; Ackland, Newgreen et al. 2003) is distinctly less mesenchymal than parental PMC42-ET cells, but both exhibit EGF- and TGFβ-inducible mesenchymal-like change. Together they provide an ideal model in which to study the regulation of epithelial-mesenchymal plasticity in a breast cancer context. We have assessed in vitro parameters including migration, 3D colony formation and EMT marker expression, and undertook both miRNA profiling (mirVana probe set V1, Ambion) and alternative splice usage (Affymetrix human 1.0 ST whole genome exon arrays) analysis. Several miRNAs were expressed differently in the two sublines and/or up- or down-regulated in response to EMT-inducing treatments. Relative to the mesenchymal ET subline, the, miR-200 family members were elevated in the epithelial LA subline, where a corresponding loss of Zeb1 expression was seen. The LA subline also showed reduced E-Cadherin promoter methylation, and increased methylation of the Zeb1 promoter. Manipulation of the miR 200 family affected the EMT marker expression in these cells, as did Zeb1 suppression with shRNA. Matrigel invasion was also inhibited with Zeb1 knockdown. Additional gene expression changes and alternative splice usage, promoter methylation changes, and miR expression changes are under study. These studies may identify molecules and pathways that are important in cell specification across the epithelial mesenchymal axis, and represent diagnostic and therapeutic targets in breast cancer. Ackland, M. L., A. Michalczyk, et al. (2001). “PMC42, A novel model for the differentiated human breast.” Exp Cell Res 263(1): 14-22. Ackland, M. L., D. F. Newgreen, et al. (2003). “Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells.” Lab Invest 83(3): 435-48. Whitehead, R. H., I. Bertoncello, et al. (1983). “A new human breast carcinoma cell line (PMC42) with stem cell characteristics. I. Morphologic characterization.” J Natl Cancer Inst 70(4): 649-61. Whitehead, R. H., P. Monaghan, et al. (1983). “A new human breast carcinoma cell line (PMC42) with stem cell characteristics. II. Characterization of cells growing as organoids.” J Natl Cancer Inst 71(6): 1193-203. 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 3428. doi:10.1158/1538-7445.AM2011-3428
Laparoscopic Cholangiography in the Diagnosis of Cholestasis: Results of 48 Cases
Authors: G. Gibertini, N. Cortesi, G. Canossi, A. Manenti, G. Gibertini
Journal: Endoscopy (1973)

The authors report their own experience of 48 laparoscopic cholangiographies, performed in patients with cholestasis. This technique was able to determine the nature of the jaundice in 45 cases: intrahepatic cholestasis in 16 and extra-hepatic in 29, secondary to neoplastic obstruction (18 cases), stones (10 cases), and narrowing of the common hepatic duct (1 case). The authors hope that laparoscopic cholangiography, a simple and useful technique, may be more widely used, and its true indications carefully followed.
AB1050 Foot Pain Symptoms in Rheumatoid Arthritis is IT Important?
Authors: F.A.B. Ibrahim, P. O'Connell
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Foot pain is common symptom in rheumatoid arthritis however the prevalence remained undetermined, further clinicians overlook seeking information about foot pain which result in under treatment. Foot symptoms and signs are not involved in Disease activity scoring system (DAS28) for Rheumatoid Arthritis. <h3>Objectives</h3> We overtook study in group of patient with diagnosis of Rheumatoid arthritis to see how common is foot pain and how was it managed. <h3>Methods</h3> We overtook study in 76 patients with established diagnosis of Rheumatoid arthritis who attended the Rheumatology out patient9s clinic by filling questionnaire about foot pain symptoms and subsequently their medical notes, laboratory results and radiology results reviewed. The study was approved by local ethical committee. <h3>Results</h3> The total number of the patients was 76, of which 24 males and 52 females. The average age was 60.41 years old (range 25 to 90 years old) and the average duration of the disease was more than 10 years. About 70% of the study group have sero-positive Rheumatoid arthritis and 20% have sero-negative RA and the rest were not characterised. From the study group 88% reported foot pain symptoms at some stage, from those more than half of them reported foot pain symptoms as early symptoms of their presentation and about 3 out of 4 (75%) considered it as one of their main problems. The foot pain reported in the plantar aspect in the most of the patients 67%. 35% of the patients were reported to have definitive erosive changes in their plain film x ray however about 5% of the study group have erosive changes and they never experienced foot pain. Just about 31% of our study group voluntarily had discussion about foot pain with their doctors in the clinic, for that reason just about 37% referred and assessed by physiotherapist and about 31% had cushion or insole made for them as modality of treatment. <h3>Conclusions</h3> Foot pain is one of the most common and genuine symptom in Rheumatoid arthritis however is hasn9t been addressed sufficiently for that foot pain in Rheumatoid Arthritis patients is always needed to be looked for by the Rheumatologist so can be managed properly which reduce the patients9 disability and symptomatology <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4629
Changes in Bronchial Epithelium in Relation to Cigarette Smoking, 1955–1960 vs. 1970–1977
Authors: Oscar Auerbach, E. Cuyler Hammond, Lawrence Garfinkel
Journal: New England Journal of Medicine (1979)

To test the hypothesis that the reduction in tar and nicotine content of cigarette smoke that began in the 1950s should be reflected by the histologic changes in the bronchial epithelium of cigarette smokers, 20, 424 sections taken at autopsy from the bronchial tubes of 445 men (non-lung-cancer deaths) were examined microscopically in random order. There were 211 men who died in 1955-1960, of whom 154 smoked regularly, and 234 men who died in 1970-1977, of whom 181 were regular smokers. Changes studied included basal-cell hyperplasia, loss of cilia and occurrence of cells with atypical nuclei. In both periods studied these histologic changes occurred far less frequently in nonsmokers than in cigarette smokers and increased in frequency with amount of smoking, adjusted for age. Sections with advanced histologic changes in those dying in 1955-1960 occurred in 0 per cent of nonsmokers, in 2.6 per cent of those smoking one to 19 cigarettes a day, in 13.2 per cent of those smoking 20 to 39 and in 22.5 per cent of those smoking 40+ cigarettes a day. In those who died in 1970-1977 the percentages were 0, 0.1, 0.8, and 2.2, respectively.
Abstract 4179: Quercetin inhibits growth of pancreatic cancer in vitro and in vivo
Authors: Eliane Angst, Jenny L. Park, Aune Moro, Qing-Yi Lu, Jonathan C. King, Vay Liang W. Go, Howard A. Reber, Guido Eibl, O. Joe Hines
Journal: Cancer Research (2010)

Abstract Background and Aim: Polyphenols are common constituents of many fruits and vegetables, and have recently gained interest as potential therapeutic agents for various human malignancies. The most abundant of these polyphenols are flavonoids - quercetin being the most ubiquitous. The aim of this study was to assess the growth-inhibitory and anti-angiogenic properties of quercetin on pancreatic cancer (PaCa) cells in vitro and in vivo. Methods and Results: Using cell count and BrdU assay, we measured a dose-dependent inhibition of cell proliferation by quercetin (0-75µM) for MIA PaCa-2 (MP) and BxPC-3 (Bx) cells (p&amp;lt;0.001 at 30µM). Quercetin (10 µM) increased apoptosis by 22% and 8% in MP and Bx, respectively (p&amp;lt;0.05). Further, quercetin (10 µM) inhibited mRNA and protein expression of the pro-angiogenic chemokine CXCL8 (p&amp;lt;0.05) in both cell lines as measured by ELISA and real-time PCR. Conditioned media from PaCa cells treated with 50 µM quercetin reduced endothelial cell tube formation by ∼50% compared to control (p&amp;lt;0.05). A feeding study was conducted utilizing an orthotopic xenograft model of PaCa in nude mice. Luciferase-expressing MP (3×106) cells were injected subcutaneously into the flank of donor mice. After four weeks, 1 mm3 donor tumor sections were transplanted into the pancreatic tail of recipient mice. These animals were randomly allocated to control diet or 1% quercetin diet groups utilizing the AIN93G-based diet (n=12 per group). In addition, 6 mice from each group were injected weekly with gemcitabine (120 mg/kg mouse, i.p.). Animals were imaged weekly after tumor implantation until sacrifice at 6 weeks. Light emission was reduced in animals receiving quercetin, gemcitabine, and both treatments by 12%, 8%, and 16%, respectively at day 24. Furthermore, CXCL8 serum levels were significantly reduced in the quercetin/gemcitabine group (p&amp;lt;0.001). Using HPLC analysis, quercetin and its metabolite, isorhamnetin, were detected in tumor tissues (2.6 ± 2.7 and 2.1 ± 0.9 nmol/gram, respectively). Conclusion: Quercetin significantly inhibits the growth of PaCa in vitro and in an orthotopic murine model. PaCa growth was inhibited utilizing a bioavailable quercetin preparation in the diet. Quercetin may, in part, be acting through a reduction of angiogenesis. From this data we surmise that quercetin may be useful as an adjunct to current treatment for pancreatic cancer. 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 4179.
Serum Antibodies to the Deleted Dystrophin Sequence after Cardiac Transplantation in a Patient with Becker's Muscular Dystrophy
Authors: Reginald E. Bittner, Sigrid Shorny, Berthold Streubel, Christoph Hübner, Thomas Voit, Wolfram Kress
Journal: New England Journal of Medicine (1995)

To the Editor: In their study of the efficacy of high-dose chemotherapy and autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma who respond slowly to chemotherapy, Verdonck et al. (April 20 issue) 1 used response criteria that may have influenced the outcome.A variety of criteria have been proposed to assess response in patients with lymphoma, but the most widely accepted are those ratified at the Cotswolds meeting, 2 which define a partial remission as "a decrease by at least 50 percent in the sum of the products of the largest perpendicular diameters of all measurable lesions."In contrast, Verdonck et al. considered patients with a reduction in tumor diameters of 25 percent or more to have had partial remissions.Thus, some of the randomized patients may not have fulfilled widely accepted criteria for an objective response.Did the outcome of patients with 25 to 50 percent reductions in tumor diameters differ from that of patients with a greater degree of cytoreduction?It is possible that the patients most likely to benefit from early intensified therapy are those who have not had even a partial response after three cycles of standard therapy.Do the authors have any data on patients considered to be nonresponsive after three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)?Did any of these patients proceed directly to dose-intensive therapies, and what was their ultimate outcome?Parkville, Victoria 3050,
AMC Recruits New Director, Rebuilds Image
Authors: Kate Ruddon
Journal: JNCI Journal of the National Cancer Institute (1989)

AMC Recruits New Director, Rebuilds Image Get access Kate Ruddon Kate Ruddon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 13, 5 July 1989, Pages 977–978, https://doi.org/10.1093/jnci/81.13.977 Published: 05 July 1989