tbuckley/cabot-search huggingface dataset:
International Breast Cancer Research: Launching an Expedition to the Moon.
Authors: M. Piccart
Journal: Cancer Research (2009)

Abstract In his State of the Union address in 1971, President Nixon launched a "war on cancer" by calling for the "same kind of concentrated effort that split the atom and took man to the moon" to be turned towards conquering cancer. Since this landmark address, great strides have been made in the war on breast cancer. Lumpectomy with adjuvant radiotherapy, sentinel lymph node dissection, and adjuvant systemic therapy in the form of chemotherapy, hormonal therapy and trastuzumab have improved the quality of life and long-term survival of women diagnosed with early breast cancer. International collaboration involving research groups and initiatives such as the Early Breast Cancer Trialists' Collaborative Group quinquennial overviews has provided the clinical trials infrastructure and framework necessary to synthesize the evidence-based data upon which these gains have been achieved. Despite these successes, the pathway to new drug development and improved medical effectiveness today is costly, labor-intensive, and far too slow for our patients. Over the last decade, the advent of molecular technologies has dramatically improved our understanding of the biology of breast cancer. We now have targeted therapies available to inhibit specific signaling pathways that are aberrant in subpopulations of breast cancer. To further improve breast cancer care, we must fundamentally rethink how translational research is performed in clinical trials. The challenge of making personalized medicine a reality demands the launch of an expedition taking us to and beyond the moon: it will involve clinicians, basic scientists, bioinformaticians, statisticians, industry sponsors, regulators, and patients in new partnership that is committed to changing the vision, culture and methodology of breast cancer research. The Breast International Group's efforts in this direction will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr W1-1.
Abstract 136: Statins and breast cancer mortality.
Authors: Teemu J. Murtola, Kala Visvanathan, Miia Artama, Harri Vainio, Eero Pukkala
Journal: Cancer Research (2013)

Abstract Background: Breast cancer is a common malignancy and cause of cancer death. Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could have beneficial effects against recurrence and progression of breast cancer. We evaluated breast cancer-specific and overall mortality among statin users in a cohort of breast cancer patients. Methods: Our study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use during these years was obtained from a national prescription database. We used Cox proportional hazards regression method to estimate mortality among statin users separately for pre- and post-diagnostic usage. Results: A total of 4,169 participants had ever-used statins. During the median follow-up of 3.25 years (range 0.08-9.0 years), a total of 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. Post-diagnostic statin use was inversely associated with breast cancer mortality (participants with localized tumors: HR 0.33, 95% CI 0.24-0.42; metastatic tumors: HR 0.52, 95% CI 0.31-0.86) and also overall mortality. The association between statin use and mortality was dose-dependent. In stratified analyses, the reduction did not significantly vary by lipophilicity of statins. Additionally, long-term pre-diagnostic statin use was also associated with lower breast cancer mortality. Conclusion: Lower breast cancer mortality observed for both pre-diagnostic and post-diagnostic statin use suggests that statins could lower risk of death in breast cancer patients. A clinical trial testing statins’ effect on survival in breast cancer patients is feasible. Citation Format: Teemu J. Murtola, Kala Visvanathan, Miia Artama, Harri Vainio, Eero Pukkala. Statins and breast cancer mortality. [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 136. doi:10.1158/1538-7445.AM2013-136
Expert Committee Examines Measures of Progress
Authors: C. K. Wittenberg
Journal: JNCI Journal of the National Cancer Institute (1988)

Expert Committee Examines Measures of Progress Get access Clarissa K. Wittenberg Clarissa K. Wittenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 12, 17 August 1988, Pages 894–895, https://doi.org/10.1093/jnci/80.12.894-a Published: 17 August 1988
Abstract 2643: A highly versatile nanoplatform for the treatment and imaging of cancers
Authors: Kit S. Lam, Luo Juntao, Kai Xiao, Yuan-pei Li, Joyce Lee, Nianhuan Yao, Wenwu Xiao, Yabg Wang, Michael Kent, Holland Cheng, Li Xing, Gangyu Liu, Yihrong Tan
Journal: Cancer Research (2010)

Abstract We have recently developed a novel amphiphilic polymer (telodendrimer), comprised of linear polyethylene glycol and cholic acid cluster, that can self-assemble under aqueous condition to form stable micelles. We have succeeded in loading the nanoparticles with several different hydrophobic drugs. These include paclitaxel, etoposide, vincristine, and dexamethasone. This nanoplatform is highly versatile. Particle size can be readily tuned by varying the configuration and composition of the telodendrimer. Nanoparticles of various sizes loaded with DiD, a near infra-red hydrophobic dye, were prepared and their biodistribution evaluated in nude mice bearing ovarian cancer xenografts. Particles smaller than 60 nm preferentially targeted the tumors whereas particles at 150nm were found to concentrate at the liver and lung but with low tumor uptake. The surface chemistry can be easily modified by tethering various acidic or basic peptides to the distal polyethylene glycol tail of the telodendrimers. Undesirable liver uptake was very high for those nanoparticles with high surface charges, either positive or negative. In contrast, liver uptake was very low but tumor uptake was very high when the surface charge was neutral. Ligation of tumor targeting ligands to the particle surface further improved tumor targeting and intracellular uptake at the tumor site. In addition to xenograft models, we have also demonstrated that the nanoparticles could preferentially target early spontaneous mammary tumors of PyV-MT transgenic mice. We have just completed a Phase I study of placiltaxel-loaded nanoparticles in companion dogs with lymphoma and showed that the drug is safe. The nanoparticles are stable both in vitro and in vivo. Additional stability of the nanoparticles can be achieved by chemical stitching of adjacent telodendrimers after micelle formation. The telodendrimer can be easily radioiodinated with [I-131]-PIB, and the resulting radio-labeled nanoparticles can be used for both radioimaging and radiotherapy. Very recently, we have succeeded in loading the nanoparticles with bortezomib (a proteasome inhibitor) to high level. We are currently evaluating the in vivo anti-tumor activities of the bortezomib nanoformulation in xenograft lymphoma as well as ovarian cancer models in nude mice. This new class of nanotherapeutics shows great promise in future cancer therapy and imaging. 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 2643.
Abstract 2790: Discovery of novel Pim-1 inhibitors
Authors: Yibin Xiang, Bradforth H. Hirth, Jinyu Liu, Markus Metz, Gary Asmussen, Hans-Peter N. Bieman, Maria Fitzgerald, Trish Fremgen, Katherine C. Jancsics, Michael Kothe, Andrew T. Papoulis, David J. Stepp, Ronnie Wei, Renato Skerlj
Journal: Cancer Research (2011)

Abstract Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. Recently, Pim-1 has been implicated in multiple human cancers, including prostate cancer, acute myeloid leukemia and other hematopoietic malignancies. Primarily expressed in spleen, thymus, bone marrow, prostate, oral epithelial, hippocampus and fetal liver cells, Pim-1 has also been found to be highly expressed in cell cultures isolated from human tumors. As part of our continuing efforts to identify potential protein targets and inhibitors in the area of cancer treatment, we selected Pim-1 target and used fragment drug discovery platform to undertake the efforts in identification of novel inhibitors. Over 1800 fragments have been screened using SPR binding assay, followed by PIM1 kinase inhibition assay. Among many active fragments, we identified an interesting small fragment, 5-bromobenzofuran-2-carboxylic acid (1), which has IC50 of 8.1 uM in the Pim-1 kinase inhibition assay. The X-ray structure of 1 binding to Pim-1 revealed that the oxygen of the benzofuran is positioned towards the hinge site while the carboxylic acid interacts directly with the Lys-67. Guided by the X-ray structures, we generated many more potent inhibitors, among which, compound 2 with an aminicyclohexayl moiety at the 7-position is one of the most potent inhibitor with IC50 of 0.001uM in Pim-1 kinase inhibition assay. X-ray structure of 2 binding to Pim-1 indicated that compound 2 gained additional interactions by directly interacting of its nitrogen atom of the aminocycloheaxyl group with Asp127 as well as interacting through water bridges with Glu170 and Asn 171. Compound 2 has also potent activity in inhibiting Pim-2 with IC50 of 0.004 uM while is highly selective against most kinases in the Ambit kinase panel. 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 2790. doi:10.1158/1538-7445.AM2011-2790
Abstract 2504: Defining the contribution of the extracellular domain of ICAM-2 to the non metastatic phenotype of neuroblastoma cells using chimeric fusion proteins
Authors: Joseph M. Feduska, Karina J. Yoon
Journal: Cancer Research (2012)

Abstract Neuroblastoma (NB) is the most common extracranial pediatric cancer, accounting for 15% of all childhood cancer deaths. Recently, our lab reported the novel finding of ICAM-2 expression in NB cell lines and primary NB tumor cells. Interestingly, ICAM-2-expressing NB cells exhibited decreased motility in vitro and decreased metastatic potential in vivo. In these ICAM-2-expressing non-metastatic NB cells, the cytoplasmic domain of ICAM-2 interacted with β-actinin, which in turn interacted with actin, leading to subsequent redistribution of actin fibers to a non-motile state. The goal of the current study is determining the potential role of the ICAM-2 extracellular domain in NB metastasis development. Therefore, we constructed a series of chimeric fusion proteins, one of which consists of the extra cellular domain of CD89 with the transmembrane and cytoplasmic domains of ICAM-2 (CD89αED). CD89 is the receptor for IgA, and bears striking similarity to ICAM-2 in terms of size (287AA vs. 275AA, respectively) and structure. Both are immunoglobulin superfamily members with two Ig-like domains, six extracellular N-glycosylation sites, and short cytoplasmic domains. Furthermore, there is no literature implicating CD89 in cancer progression. This construct was stably transfected into a non-ICAM-2 expressing SK-N-AS NB cell line, and protein expression was confirmed by flow cytometry and western blot. Our preliminary data showed distinct phenotypic differences between NB cells stably transfected with the CD89αED construct compared to wild type ICAM-2. In scratch assays, CD89αED cells showed faster migration ability than ICAM-2 wt (75% vs. 50% wound closure) at 72 hour time points. Furthermore, in anchorage-independent colony growth in soft agar, CD89αED cells formed a significantly (P &amp;lt; 0.001) higher number of colonies compared to ICAM-2 wt. Ongoing work focuses on determining the effect of CD89αED on F-actin modification and regulation of potential downstream signaling pathways. This work was supported by the UAB Comprehensive Cancer Center Young Supporters Board - New Faculty Development Award 2010 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 2504. doi:1538-7445.AM2012-2504
The role of EUS for diagnosis of pancreatic cysts: observe, needle, or brush?
Authors: A. Sahai
Journal: Endoscopy (2010)

It is probably fair to say that most endosonographers are generally “pro” cyst fluid analysis (CFA) for cystic pancreatic lesions (CPLs). On the face of it, the ability of endoscopic ultrasonography (EUS) to provide detailed imaging, tissue, and cyst fluid for analysis makes it a seemingly powerful diagnostic tool for these potentially malignant lesions.
Effect of cabazitaxel on the growth of human castration-refractory prostate cancer cells in vitro compared to docetaxel and on the anti-tumor properties of the angio-inhibitor PEDF in vivo.
Authors: Thomas Nelius, Courtney Jarvis, Dalia Martinez-Marin, Stephanie Filleur
Journal: Journal of Clinical Oncology (2015)

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.
Benefits of an honest admission
Authors: A G Elder, E. B Macdonald, I. Madan
Journal: BMJ (1998)

clinical negligence, and hence costs, or at least to moderate the expected increase in them. 2 These costs, of precaution and administration, as well as of accidents themselves, will not all fall necessarily on the NHS, let alone on any one purchaser or provider.Overall minimisation of NHS costs would require some restriction on expenditures for the actual and possible victims of accidents.Court awards may be contested, settlement offers reduced or delayed, or clinical precautions stop short of the maximum possible, for example.Until NHS organisations always prioritise minimisation of overall costs borne by victims of medical accidents, even at the expense of the NHS budget, pressures on resources mean that there is no guarantee that victims will retain even their current standing among NHS priorities for resources.
THU0510 Turkish Lupuspro: Cross Cultural Validation Study for Lupus
Authors: A. Kaya, B. Goker, E. S. Cura, M. E. Tezcan, A. Tufan, R. Mercan, B. Bitik, S. Haznedaroglu, M. A. Ozturk, J. A. Block, R. A. Mikolaitis-Preuss, M. Jolly
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> LupusPRO is a disease targeted patient reported outcome measure that was developed and validated in patients with Systemic Lupus Erythematosus (SLE) in the USA. Its Spanish vesion has also been recently validated. <h3>Objectives</h3> We aimed to develop and validate the Turkish version of the LupusPRO. <h3>Methods</h3> The Turkish version was prepared by forward and backward translations of the 43 item English LupusPRO (T1) by native Turkish speakers and was pretested in five Turkish individuals living in the USA. The final Turkish version was then offered. Each subject met ACR classification criteria for SLE and resided in Turkey. SF-36 (Turkish) was also administered. Disease activity was assessed using the physician's global assessment (PGA) and SELENA-SLEDAI, and flare (Yes/No). Disease damage was assessed using the SLICC-ACR SDI. For test-retest reliability (TRT), patients were instructed to re-do the Turkish LupusPRO test within 2-3 days. Internal consistency reliability (ICR), criterion validity (against measures of disease activity or health status) and convergent validity (corresponding domains of the SF36) were also assessed. A 'p-value' &lt;0.05 was considered significant. The conceptual framework of the LupusPRO was evaluated using confirmatory factor analysis appropriate for categorical data. <h3>Results</h3> 102 SLE subjects (94% women) were enrolled. The mean ±SD age (yrs) and disease duration were 39.0 ±11.7 and 5.0 ±4.6, respectively. The mean ±SD, SLEDAI and SDI scores were 3.1 ±3.7 and 0.52 ±0.75, respectively. There were 25 patients who had flares. PGA scores were; 0 for 26%, 1 for 60%, 2 for 11% and, 3 for 5% of the patients. 42 patients were included in the test-retest analysis. Psychometric properties of the Turkish LupusPRO are shown in the table. Item to factor loadings representing the hypothesized item to scale relationships were satisfactory. The model fit for the hypothesized item to scale relationships was also satisfactory. <h3>Conclusions</h3> The Turkish version of the LupusPRO is valid and appears to perform comparably to the English version. It can be used as a patient-reported outcome parameter in clinical trials, as well as longitudinal studies for testing responsiveness to change. <h3>Disclosure of Interest</h3> A. Kaya: None Declared, B. Goker: None Declared, E. Cura: None Declared, M. Tezcan: None Declared, A. Tufan: None Declared, R. Mercan: None Declared, B. Bitik: None Declared, S. Haznedaroglu: None Declared, M. Ozturk: None Declared, J. Block: None Declared, R. Mikolaitis-Preuss: None Declared, M. Jolly Grant/research support from: Lupus Foundation of America, MedImmune, Glaxo SmithKline
PMO-057 Dietary intervention for individuals with spinal cord injuries—a 2 year report on the spinal clinic for obese out-patient project (scoop)
Authors: S S H Wong, A Graham, A Jamous, L Spillman, G Grimble, A Forbes
Journal: Gut (2012)

<h3>Introduction</h3> Obesity is common after spinal cord injuries (SCI)<sup>1</sup> and it is associated with chronic nutrition related complications. We previously reported that a simple dietetic-intervention can help SCI patients to lose weight without compromising lean body mass.<sup>2</sup> <h3>Methods</h3> The present study aimed to assess the effectiveness of a dietitian led weight management clinic. Thirty-one individuals (52.4±11.5 years; body mass index (BMI): 32.9 kg/m<sup>2</sup>; 41% female) with SCI were referred for consultation to include nutritional advice and cognitive behaviour therapy in three consultations over 4 months. Outcomes measures included body composition from anthropometric measurements of BMI, mid upper-arm circumference (MUAC), triceps skinfold thickness (TSF) and mid-arm muscle circumference (MAMC), sitting blood pressure and dietary assessment of nutrient intake by 7-d food diary. <h3>Results</h3> Of the thirty-one individuals, 15 (48.4%) reported one or more co-morbidities. Mean weight loss was 4.5 kg (SD 6.2) at week 16. Analysis of the pre- to post-intervention difference (using paired t-test) showed a significant reduction in weight (104.2 vs 100.4 kg, p=0.001), BMI (34 vs 33.1 kg/m<sup>2</sup>, p=0.004), total energy intake (6.84 vs 5.62 MJ/d, p=0.029), total fat (p=0.005), saturated fat (p=0.001) and alcohol (p=0.003). No significant changes were found in MUAC, TSF, MAMC and sitting blood pressure post intervention. We noted a significant reduction in MAMC at 1-year follow-up (30.2 vs 27.1 cm, p&lt;0.001). The 7-d food diary showed an average energy intake of 7.65 MJ/d, which is 15% below the estimated requirement. <h3>Conclusion</h3> The findings of this study suggest that current guidance overestimates nutritional requirements in the SCI population, and that simple dietetic-intervention could help overweight SCI patients to achieve weight loss, but that it may not be sufficient to stimulate/maintain muscle mass long term. Further research is warranted to test whether combining lifestyle and intensive physical therapy could reduce long-term muscle wasting. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Gupta N,</b><i>et al. Spinal Cord</i> 2006;<b>44</b>:92–4. 2. <b>Wong S,</b><i>et al. Food Nutr Sci</i> 2011;<b>2</b>:901–7.
Phase I Trial of 5-FU, Docetaxel and Nedaplatin Combination Therapy for Metastatic Esophageal Cancer
Authors: Nishina Shinichi, Ueda Shinya, Nonagase Yoshikane, Okabe Takafumi, Kawakami Hisato, Sakiyama Tsutomu, Tamura Takao, Nakagawa Kazuhiko
Journal: Annals of Oncology (2014)