tbuckley/cabot-search huggingface dataset:
Abstract 1067: Targeting the fibroblast growth factor receptor axis in malignant pleural mesothelioma
Authors: Mir Alireza Hoda, Karin Schelch, Christine Pirker, Bahil Ghanim, Thomas Klikovits, Viktoria Laszlo, Ulrike Setinek, Martin Filipits, Balazs Dome, Balazs Hegedues, Brigitte Marian, Bettina Grasl-Kraupp, Walter Klepetko, Walter Berger, Michael Grusch
Journal: Cancer Research (2012)

Abstract Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy. Fibroblast growth factors (FGF) and their high-affinity receptors (FGFR) contribute to malignant growth in several tumor types including thoracic malignancies while a role in MPM remains widely undefined. Therefore, aim of the present study was to investigate the expression and impact of FGFs and FGFRs in MPM and to evaluate their potential suitability as new therapeutic targets. Material und Methods: Expression of all known FGF and FGFR genes was assessed by expression array analysis and confirmed by qRT PCR in MPM cell lines (n=10) and normal mesothelial cells. Selected FGFs were also investigated by immunohistochemistry on tissue samples. FGFR-specific tyrosine kinase inhibitors and an adenovirus expressing dominant-negative FGFR1 were used to block FGF signal transduction in MPM cell models. MTT and clonogenic assays as well as spheroid formation assays and videomicroscopy were performed to analyze cell growth, survival and migration. The effect on downstream signal transduction was assessed by immunoblotting with phosphorylation site-specific antibodies. Results: FGFR1 as well as the ligands FGF2 and FGF18 were highly expressed in almost all MPM cell lines investigated. Moreover, immunohistochemistry demonstrated high FGF expression also in tissue sections. Stimulation with exogenous FGF2 in contrast, led to a remarkable increase in cell migration and clonogenic growth. In contrast, inhibition of FGFR1 by the specific small molecule kinase inhibitor PD166866 lead to decreased proliferation, survival, migration and spheroid formation in the majority of cell lines tested. Adenoviral expression of dominant-negative FGFR1 further confirmed these results. In addition, concomitant FGFR inhibition increased the efficacy of currently used chemotherapeutic agents such as cisplatin. Also combination of FGFR inhibition and radiation lead to enhanced cytotoxicity. Conclusion: Taken together, these data suggest that FGFR signals contribute to proliferation, survival, migration and chemotherapy resistance of MPM cells and their inhibition should be further evaluated as a potential new treatment strategy in MPM. 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 1067. doi:1538-7445.AM2012-1067
SAT0334 Radiographic joint damage as a predictor of short-term clinical outcome of total knee replacement surgery
Authors: T.N. De Boer, P.M. Welsing, A.M. Huisman, A.A. Polak, W.H. Noort-vanderLaan, S.C. Mastbergen, F.P. Lafeber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is a slowly progressive degenerative joint disorder most frequently seen in the middle aged and older people. OA has a high prevalence causing pain and loss of function. There is still no cure for the disease. The current treatment of OA is initially conservative, predominantly focused on the relief of pain, minimizing functional disability, and limiting progression of joint damage. When conservative treatment fails and joint preserving surgery is not or no longer indicated, knee replacement of the affected joint becomes necessary. A proper selection of patients for total knee replacement surgery is crucial in the light of the exponentially growing numbers with its socioeconomic impact. <h3>Objectives</h3> The present study evaluated potential radiographic and clinical predictors for clinical outcome of knee replacement surgery in a cohort of patients with end-stage knee OA treated in regular practice in an orthopedic department of a general hospital in the Netherlands. <h3>Methods</h3> Patients (172) with severe OA who were eligible for total knee replacement surgery in a general hospital were included. Demographics, clinical, and radiographic data were collected. WOMAC data were collected prospective pre-treatment, and after surgery (post-treatment). OARSI-OMERACT response criteria based on WOMAC questionnaires were used to evaluate clinical success. Severity of radiographic joint damage was evaluated according to Kellgren &amp; Lawrence and Altman atlas. Pre-treatment characteristics associated with responder status were investigated using multivariate logistic regression analyses. <h3>Results</h3> Patients showed on average a clear improvement in WOMAC scores at a mean of 18 months post-treatment (33.0±20.0 improvement in WOMAC pain). Based on WOMAC response criteria 55% of the patients were classified as responders. In multivariate logistic regression, younger age (OR=0.930; 95%CI: 0.864-1.002), more severe pain (OR=0.966; 95%CI: 0.937-0.997) and more radiographic damage (OR=3.456; 95%CI: 1.568-7.618) was associated with good response. Results were similar when patients with missing outcomes were classified as non-responders or responders in a sensitivity analysis. <h3>Conclusions</h3> This study shows that still a significant number of patients do not have a good response to joint replacement surgery. A good response was clearly associated with more severe radiographic joint damage and possibly with age and WOMAC pain at time of operation. These results need further validation in larger cohorts and might become of use to a more accurate patient selection for knee replacement surgery. <h3>Disclosure of Interest</h3> None Declared
Leukopoietic Activity in Human Urine
Authors: William A. Robinson, Beverley L. Pike
Journal: New England Journal of Medicine (1970)

Urine from normal persons and patients with acute and chronic leukemia was tested for ability to stimulate granulocyte bone-marrow colony growth in vitro. All eight patients with chronic granulocytic leukemia had high levels of colonygrowth-stimulating activity. Six out of seven patients with acute stem-cell or acute lymphatic leukemia also had high levels, whereas nine out of 15 patients with untreated acute granulocytic leukemia had low or absent levels. In acute granulocytic leukemia, levels may rise during treatment, often becoming normal to very high with remission, only to fall again to subnormal levels with relapse.
PROGNOSTIC IMPACT OF UNRECOGNIZED MYOCARDIAL SCAR IN NON-INFARCT RELATED CORONARY TERRITORIES DETECTED BY CARDIAC MAGNETIC RESONANCE IMAGING IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Taku Omori, Tairo Kurita, Kaoru Dohi, Akihiro Takasaki, Tomoyuki Nakata, Shiro Nakamori, Kakuya Kitagawa, Kozo Hoshino, Hajime Sakuma, Masaaki Ito
Journal: Journal of the American College of Cardiology (2016)
Abstract 2108: Prevalence of mutations in MSH6, PMS1 and PMS2 gene in Brazilian families with Lynch syndrome
Authors: Felipe C. Silva, Giovana T. Torrezan, Bianca G. Lisboa, Erika M. Santos, Israel Gomy, Benedito M. Rossi, Fabio O. Ferreira, Dirce M. Carraro
Journal: Cancer Research (2012)

Abstract Background: Lynch syndrome (LS) is an autosomal dominant disorder predisposing to colorectal cancer and increased risk for cancers of the stomach, small intestine, hepatobiliary system, kidney, ureter, ovary, and sebaceous tumors. Germline mutations in the MMR genes MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), post- meiotic segregation increased 1 (PMS1) or post- meiotic segregation increased 2 (PMS2), are known to cause LS. While mutations in MLH1 and MSH2 gene, account for 70% - 80% of all Lynch syndrome colorectal cancers, the involvement of the MSH6, PMS2 and PMS1 gene is continually rising. Altogether, MSH6, PMS1 and PMS2 mutations account for 5-20% of kindreds in which MSH2 and MLH1 mutations are excluded. Objective: The aim of the study was evaluate the frequency of mutations in MSH6, PMS1 and PMS2 gene. Methods: Seventy one unrelated patients without MLH1/MSH2 mutations were eligible for this study. Genomic DNA was obtained from peripheral blood and primers were designed within introns of all exons of MSH6, PMS1 gene. In order to avoid the amplification of pseudogenes for the PMS2 gene, a set of four primer pairs were design. Results: Out of 71 patients, 20 fulfilled the Amsterdam criteria and other 51 fulfilled the Bethesda guideline. Four novel pathogenic mutations were detected, three in MSH6 and 1 in PMS2. In addition, 7 variants of uncertain significance were encountered, in which two of them were previously described as pathogenic. No mutations were found in PMS1 gene. Conclusion: Our data shows that 8.5% (6/71) of the individuals have mutations in MSH6 and PMS2 gene and these results strongly suggest that MSH6 and PMS2 should not be excluded from the MMR screening in Brazilian families suspected for Lynch syndrome. 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 2108. doi:1538-7445.AM2012-2108
The PIP scandal: an analysis of the process of quality control that failed to safeguard women from the health risks
Authors: Victoria Martindale, Andre Menache
Journal: Journal of the Royal Society of Medicine (2013)

Plastic surgery is a sector of medicine that continues to show strong trends in growth. In 2011, women accounted for 90% of all procedures, with breast augmentation being the most common.1 There are estimated to be a total of 130,000 women in the UK who have received breast implants and around 47,000 of these were silicone implants manufactured by the French-based company Poly Implant Prothese (PIP).2 Following the misuse by PIP of industrial grade silicone, an expert panel, chaired by Sir Bruce Keogh, was appointed by the Department of Health to investigate the consequences of this scandal. They concluded in their final report of June 2012 that ‘PIP implants have not shown any evidence of significant risk to human health’.3

We disagree with their conclusion. Here we aim to share our concerns on the regulatory and quality control procedures that failed to safeguard thousands of women from the health risks associated with PIP breast implants. In light of the current ongoing review into cosmetic surgery which is also being led by Sir Bruce Keogh, it is vital that such failings are identified and tightened to ensure such a scandal is not repeated.

What is a breast implant?




A medical prosthesis used to augment, reconstruct, or create the physical form of breasts


Modern (so-called fifth generation) breast implants usually contain either saline or a viscous silicone gel


The outer casing, or shell, is composed of durable elastic silicone manufactured through a chemical process called vulcanization in which sulphur is added to the silicone to increase durability
Abstract 3293: p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans
Authors: Peter J. Wild, Kristian Ikenberg, Thomas Fuchs, Strahil Georgiev, Aurelia Noske, Matthias Roessle, Rosmarie Caduff, Athanassios Dellas, Daniel Fink, Holger Moch, Wilhelm Krek, Ian Frew
Journal: Cancer Research (2012)

Abstract Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II carcinoma subtypes. The PI3K-Akt-mTOR signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, immunohistochemical analyses of 521 human endometrial carcinomas identified frequent mTOR pathway activation in type I as well as type II endometrial carcinoma subtypes and mTOR pathway activation and p53 expression each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the PI3K-mTOR pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and PI3K-mTOR pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. 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 3293. doi:1538-7445.AM2012-3293
[Leukemia and the Somatic Risks of Chemical Mutagens]: Discussion
Authors: C. Langley, E. B. Lewis, H. E. Sutton, R. F. Kimball, R. L. Capizzi, S. S. Epstein, C. Ramel, G. Wolff, Dr. Cumming, S. Abrahamson
Journal: Environmental Health Perspectives (1973)
Abstract 594: MDM2 inhibition by MI-219 elicits differential molecular effects in wild-type p53 lymphoma cells
Authors: Angela M. Sosin, Dajun Yang, Ramzi M. Mohammad, Ayad Al-Katib
Journal: Cancer Research (2011)

Abstract Mutations in TP53 occur in 50% of all cancers but are far less common in hematological malignancies. The activity of wild-type p53 (wt-p53) is frequently compromised in lymphomas by overexpression of MDM2. Small-molecule inhibitors (SMIs) that can disrupt the MDM2-p53 interaction and restore p53 function may be an attractive therapeutic strategy. Although response to MDM2 inhibition has previously been determined to greatly depend on p53 status, p53 functional consequences are not fully understood in the presence of MDM2 SMIs. We recently demonstrated striking growth inhibition of two different classes of MDM2 SMIs: Nutlin-3; a cis-imadiazole and MI-219; a spiro-oxindole. Growth inhibition was seen in wt-, but not mutant-, p53 lymphoma cells and did not affect MDM2 E3 ligase activity. In this study, we report that MDM2 inhibition exerts differential molecular effects in wt-p53 lymphoma cells. We found that wt-p53 cell lines, FSCCL and KM-H2, are sensitive to MDM2 inhibition in a time- and dose-dependent manner. Moreover, MI-219 showed greater potency compared to analogous concentrations of Nutlin-3. MI-219 caused more pronounced cell cycle arrest of both cell lines in G0/G1 over a 72 hour time period. Treatment stabilized and activated p53 as well as upregulated p21 and MDM2 protein levels. MG132 and cycloheximide treatments were performed in the presence or absence of MI-219 to determine whether the increase in p53 was due to dissociation from MDM2 and not increased degradation or stabilization. Co-immunoprecipitation confirmed MDM2 SMI disruption of the MDM2-p53 interaction. There was clear evidence of apoptosis in FSCCL, but surprisingly not in KM-H2, as indicated by TUNEL/PI staining (54.39% ± 4.78 vs. 1.32% ± 0.52 after 24 hours). Additionally, apoptosis markers were induced at both mRNA (p53AIP1) and protein levels (caspase-3 and PARP cleavage) after exposure to MI-219 in FSCCL compared to KM-H2. The molecular mechanisms by which MDM2 SMIs exert this differential effect are currently under investigation. Our data presents the preclinical structure for further exploration of MI-219 as a therapeutic approach in the treatment of wt-p53 lymphomas. However, based on our findings, we conclude that additional insights to p53 biology are necessary to maximize their therapeutic potential from preclinical to clinical development. 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 594. doi:10.1158/1538-7445.AM2011-594
FIRST TIME MYOCARDIAL INFARCTION IN THE HOSPITALIZED PATIENT: A REVIEW OF 3.65 MILLION ADMISSIONS FROM THE UNITED STATES NATIONAL TRAUMA DATABANK
Authors: Odunayo Olorunfemi, Gbolahan Ogunbayo, Anand Dayama, Oladimeji Akinboro, Melvin E. Stone, John McNelis
Journal: Journal of the American College of Cardiology (2016)
Tl-201 Chloride and Tc-99m MIBI Accumulation in Lung Adenocarcinoma in Patients With and Without Distant Metastases
Authors: YUKA YAMAMOTO, YOSHIHIRO NISHIYAMA, KOTARO FUKUNAGA, KATASHI SATOH, MOTOOMI OHKAWA
Journal: Clinical Nuclear Medicine (2001)

The relation between Tl-201 chloride accumulation by the tumor and its distant metastatic potential were evaluated in patients with lung adenocarcinoma and compared with the same parameters achieved using Tc-99m MIBI.Fifty-six patients with primary lung adenocarcinoma were examined before therapy was begun. They were classified according to the radiologic findings and pathologic diagnosis into two groups: distant metastases and no distant metastases. All patients underwent dual-isotope imaging with Tl-201 chloride and Tc-99m MIBI. Regions of interest were placed over the tumor uptake (T) and contralateral normal lung tissue (N) areas on one transverse view with clearly defined lesions, and the T:N ratio and retention index were calculated.The early and delayed T:N ratios and retention index using Tl-201 chloride SPECT in the distant-metastases group were significantly greater (P < 0.001 to P < 0.05) than were those in the no-distant-metastases group. There was no significant correlation between the T:N ratio and retention index and distant metastatic potential using Tc-99m MIBI SPECT.Tl-201 chloride SPECT may be more effective than Tc-99m MIBI SPECT for evaluating the distant metastatic potential of primary lung adenocarcinoma.
THU0356 Is there an Association between Skin and Joint Involvement in Patients with Psoriatic Arthritis Treated with Adalimumab? – Data-Analysis From a Large German Non-Interventional Study
Authors: F. Behrens, M. Koehm, D. Thaci, B. Krummel-Lorenz, G. Greger, B. Wittig, H. Burkhardt
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In Psoriatic Arthritis (PsA) skin and joint manifestations usually occur in parallel. To explore the association between both, severity of skin disease, joint involvement as well as characteristics of joint and skin manifestations were analysed. <h3>Methods</h3> To evaluate data from a multicenter, non-interventional study of PsA patients (n= 1918) treated at different dermatology and rheumatology centers in Germany, descriptive statistics and stepwise regression analyses were used. Patient's data were analysed empirically grouped by baseline target lesion score (TLS) into patients with mild (low TLS, ≤ 3), moderate (intermediate TLS, 4 to 10), or severe (high TLS, 11 to 15) skin disease. <h3>Results</h3> Stepwise regression analyses demonstrated no significant association between skin severity and joint manifestations at baseline or after 12 months of adalimumab (ADA) treatment. At baseline, the subgroup with high baseline TLS scores (severe skin disease) had an increased proportion of patients with moderate to severe nail psoriasis (61.6% vs 16.6% for low baseline TLS)), dactylitis (43.9% vs 29.0% for low baseline TLS), and enthesitis (24.6% vs 14.3% for low baseline TLS). The TLS at baseline was significantly correlated with nail psoriasis, the physician global assessment of overall disease activity, and concomitant treatment with methotrexate (MTX) (r &lt; 0.0001). All three TLS subgroups showed improvements in skin and joint manifestations during ADA therapy. The reduction of TLS exceeded in patients with high baseline TLS (severe skin disease) or in those who had received concomitant treatment with MTX. High body mass index (BMI) was significantly associated with a lack of improvement in cutaneous manifestations during therapy. <h3>Conclusions</h3> The severity of skin manifestations is not associated with the severity of peripheral joint disease in patients with PsA. Patients with mild skin disease may have extensive musculoskeletal involvement and vice versa. ADA is effective in PsA treatment regardless of baseline skin severity. <h3>Disclosure of Interest</h3> F. Behrens Grant/research support from: Abbott, Consultant for: Abbott, M. Koehm Grant/research support from: Abbott, D. Thaci Grant/research support from: Abbott, Consultant for: Abbott, B. Krummel-Lorenz Grant/research support from: Abbott, Consultant for: Abbott, G. Greger Employee of: Abbott, B. Wittig Employee of: Abbott, H. Burkhardt Grant/research support from: Abbott, Consultant for: Abbott
Abstract ES1-1: Advances in the Neurosurgical Management of CNS Metastases
Authors: Claus EB
Journal: Cancer Research (2010)

Abstract As the overall survival of patients with metastatic breast cancer improves, greater attention has been drawn to involvement specific to the central nervous system (CNS). Brain metastases are the most common intracranial tumor in adults with breast cancer representing the second most common type of CNS brain metastasis. These lesions are thought to develop in up to 20% of breast cancer patients with over 15,000 new cases predicted in the United States each year. Spinal metastases, some with involvement of the spinal cord, are also a frequent occurrence in the breast cancer patient with up to 30% of patients developing this form of the disease. Unfortunately, new systemic therapies for CNS metastases have had little impact on disease control, a critical factor in the improvement of quality of life and survival for this group of patients. Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database reveal that one third of intra-cranial and one-half of spinal breast cancer patients with neurosurgically treated CNS metastases are alive at 1 year and that the overall post-operative survival has increased over time for spinal fusion procedures. We propose to review the current state of knowledge, the existing barriers to more successful neurosurgical treatment, and the future goals for treating CNS metastases with neurosurgical intervention. We will 1) review the clinical factors associated with the development of CNS metastases, 2) summarize current neurosurgical treatment strategies with evidence-based outcome data, 3) highlight possible directions for future research efforts. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES1-1.
Emphysematous Aortitis after Endovascular Graft
Authors: Yi-Luan Huang, Ming-Ting Wu
Journal: New England Journal of Medicine (2014)

A 75-year-old man presented to the ED with a 5-day history of back pain and intermittent fever. He had undergone endovascular aortic repair of a thoracic aortic aneurysm 7 years previously.
Scintigraphy of Cubital Bursitis
Authors: Siri Kannangara, Duminda Munidasa, Jana Kross, Hans Van der Wall
Journal: Clinical Nuclear Medicine (2002)

A 50-year-old man with psoriatic arthropathy was examined for a painful mass in the left cubital fossa. The clinical findings indicated a tumor or infection. Computed tomographic scanning and bone scintigraphy also raised the possibility of a malignant lesion. Surgical exploration revealed that the mass was a chronically inflamed bicipitoradial bursa adherent to the biceps tendon. This is a rare condition, with only a handful of cases described in the literature. This is the first scintigraphic case reported. The imaging features of the bursa are discussed in terms of the anatomy.
BICUSPID AORTIC VALVE STENOSIS: IMPROVED OUTCOMES WITH A NEXT GENERATION TRANSCATHETER HEART VALVE IN A MULTI-CENTER STUDY
Authors: Gidon Perlman, Philipp Blanke, Danny Dvir, Gregor Pache, Thomas Modine, Marco Barbanti, Erik W. Holy, Hendrik Treede, Philipp Ruile, Franz-Josef Neumann, Caterina Gandolfo, Francesco Saia, Corrado Tamburino, George Mak, Christopher Thompson, David Wood, Jonathon Leipsic, John Webb
Journal: Journal of the American College of Cardiology (2016)