tbuckley/cabot-search huggingface dataset:
Abstract 4549: A comparative efficacy study of Saquinavir in combination with cisplatin or paclitaxel in platinum-resistant ovarian cancer cells
Authors: Terry-Ann E. Waite, Monique Reboe, Arkene Levy, Sivanesan Dhandayuthapani, Appu Rathinavelu
Journal: Cancer Research (2015)

Abstract Background and Objective: Ovarian cancer is the 7th most common cancer affecting women Worldwide which has a 5-year survival rate of 45%. First line therapy, platinum and taxol compounds, produces 60% to 80% response rates in platinum sensitive ovarian cancer. However, incidence of resistance to this therapy is high resulting in poor prognosis. The present study evaluated the comparative efficacy of Saquinavir (SAQ) in combination with Cisplatin (CIS) or Paclitaxel (TAX) versus first line therapy, CIS+TAX, in platinum-resistant OVCAR-3 cells. Method: OVCAR-3cells were treated with varying concentrations of SAQ (20μM, 40μM, 60μM and 100μM). OVCAR-3 cells were treated with SAQ (100μM), SAQ+CIS(26μM), SAQ+TAX(1.5nM) and CIS+TAX. Cells were treated over a 24hr period in triplicate. Media only and DMSO only treated cells were used as controls. The cytotoxic effect of each treatment was determined using the automated Trypan Blue exclusion protocol and DNA fragmentation assay was performed to evaluate the mechanisms of induced cell death. Results: Dose dependent and statistically significant (p &amp;lt;0.05) cytotoxic effects were seen with SAQ in OVCAR-3 cells. An IC50 value of 84μM for SAQ was determined in OVCAR-3 cells. Significant cytotoxic effects (p&amp;lt;0.05) in OVCAR-3 treated cells were observed with SAQ, SAQ+TAX, SAQ+CIS AND CIS+TAX combinations when compared to controls. However, SAQ+CIS was the only combination that showed more significant cytotoxicity when compared to CIS+TAX (p = 0.041). SAQ+CIS combination produced an average percentage cell death of 73.25% in OVCAR-3 cells. Cell death by apoptosis was confirmed from observed fragmented DNA in OVCAR-3 cells treated with SAQ+TAX, SAQ+CIS and CIS+TAX. Conclusion: SAQ+CIS produced more significant cytotoxic effect than first line therapy, CIS+TAX, in platinum-resistant ovarian cancer cells. This data supports further evaluation of SAQ for its potential utilization in the treatment of platinum-resistant ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Terry-Ann E. Waite, Monique Reboe, Arkene Levy, Sivanesan Dhandayuthapani, Appu Rathinavelu. A comparative efficacy study of Saquinavir in combination with cisplatin or paclitaxel in platinum-resistant ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4549. doi:10.1158/1538-7445.AM2015-4549
Role of chemoradiation in locally advanced pancreatic cancer: A systematic review and meta-analysis.
Authors: Adnan Nagrial, Venessa T. Chin, Chelsie O'Connor, Katrin Marie Sjoquist, Lorraine A. Chantrill, Andrew Victor Biankin, Desmond Yip
Journal: Journal of Clinical Oncology (2015)

348 Background: The role of combined modality therapy in the management of locally advanced pancreatic cancer (LAPC) is uncertain. Current guidelines recommend combined modality therapy for select patients. We sought to review the evidence for combined modality versus single modality therapy in LAPC. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) comparing chemoradiation versus chemotherapy alone as well as chemoradiation versus radiation alone in patients with LAPC. Methods: We searched MEDLINE, EMBASE and CENTRAL from inception to Oct 2013 for RCTs comparing chemotherapy alone versus chemotherapy plus radiation and radiation alone versus chemotherapy plus radiation. We also searched abstracts of major cancer meetings from 1990 to 2013. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), response rate and adverse events. Hazard ratios (HR), confidence intervals (CI) and p-values (p) were estimated with a random-effects model due to the heterogeneity of included studies using Revman 5.3. Results: We included 7 eligible trials including 753 patients. Induction chemotherapy was delivered prior to randomisation in one study. Chemoradiation versus chemotherapy (n= 5 studies) did not improve PFS (HR 1.02, 95% CI 0.87 - 1.20, p = 0.80) or OS (HR 0.91, 95% CI 0.64 - 1.31, p = 0.61). However, chemoradiation versus radiation (n=2 studies) improved PFS (HR 0.63, 95% CI 0.41 - 0.96, p = 0.03) and OS (HR 0.65, 95% CI 0.43 – 0.96, p = 0.03). There was significant statistical heterogeneity in the included studies and subsequently wide confidence intervals in the pooled results. This is most likely due to the small participant numbers in each study. Adverse events were more frequent in the chemoradiation arms. Response rates were assessed in only two studies. Conclusions: Chemoradiation is not superior to chemotherapy alone in LAPC, but may be superior to radiation alone. The studies were small with significant heterogeneity. Combined modality therapy results in increased adverse events. Our results do not provide evidence for a universal standard of care, thus more studies of combined modality therapy in LAPC are needed.
MYB-FL controls gain and loss of floral UV absorbance, a key trait affecting pollinator preference and reproductive isolation
Authors: Hester Sheehan, Michel Moser, Ulrich Klahre, Korinna Esfeld, Alexandre Dell'Olivo, Therese Mandel, Sabine Metzger, Michiel Vandenbussche, Loreta Freitas, Cris Kuhlemeier
Journal: Nature Genetics (2015)
Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAF<sup>V600E</sup>-mutated melanoma.
Authors: Axel Hauschild, Jean Jacques Grob, Lev V. Demidov, Thomas Jouary, Ralf Gutzmer, Michael Millward, Piotr Rutkowski, Christian U. Blank, Beloo Mirakhur, Mary E. Guckert, R. Suzanne Swann, Patricia Haney, Anne-Marie Martin, Danielle Ouellet, Kelly Grotzinger, Vicki L. Goodman, Paul B. Chapman
Journal: Journal of Clinical Oncology (2012)

LBA8500^ The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Important Limitations in Defining the Benefits of Bariatric Surgery for Patients With Type 2 Diabetes
Authors: Simon Erridge, Swathikan Chidambaram
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The relationship between tumor size and stage in early versus advanced ovarian cancer: A retrospective chart review
Authors: L. E. Horvath, T. Werner, K. Jones
Journal: Journal of Clinical Oncology (2007)

5580 Background: Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage. Methods: This was a retrospective chart review of patients in the tumor registry in 2003 to 2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged. Results: There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p &lt; 0.001). Conclusions: Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference. No significant financial relationships to disclose.
The “Cure” for Cancer: Can the Media Report the Hope Without the Hype?
Authors: Christopher K. Daugherty
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.18.3761 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12228195 The “Cure” for Cancer: Can the Media Report the Hope Without the Hype? Christopher K. DaughertyxChristopher K. DaughertySearch for articles by this author Show More University of Chicago, Chicago, IL https://doi.org/10.1200/JCO.2002.20.18.3761 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Evaluation of HER-2 expression in breast cancer using image analysis incorporating automatic feature recognition
Authors: C. Murray, J. Maddison, C. Anderson, D. Challender, S. Palmer, J. Rodgers
Journal: Journal of Clinical Oncology (2006)

20007 The currently favoured method for evaluation of HER-2 in routine clinical practice and research studies is immunohistochemistry (IHC). As standardised scoring of protein expression, using a scale of 0 - 3+, generates a significant number of false positives, fluorescent in situ hybridisation (FISH) is used to confirm the presence of gene amplification. Both techniques are laborious, and in the case of by-eye scoring of IHC, semi-quantitative at best. We have developed a high-throughput platform for the quantitative analysis of immunostained slides, based on fast, high-resolution scanning followed by analysis of digitised images (IA) using proprietary software, and in this study compared results obtained using this platform with those obtained using conventional methods. Archival sections of primary breast cancers collected at Nottingham City Hospital in 2004 and 2005 were stained for HER-2 (Herceptest, Dako), and evaluated by eye. Equal numbers of slides from scoring categories 0–3+ were then selected for further image analysis. The digitised images were subjected to automatic delineation to define areas of tumour parenchyma, and these areas further analysed using colour segmentation. Between 100 and 2000 fields were quantified on each section. Staining was expressed as a product of field fraction of coloured pixels and optical density. The results of IA demonstrate a continuum of staining values over the four conventional by-eye categories, with a non-linear correlation to by-eye scores. Inter-sample variation was greatest in the 3+ category, although the mean was much higher than that of the 2+ samples. The 2+ samples showed some variation, with several values not rising above baseline. To further investigate the relationship between FISH scores and IA results in the 2+ category, we analysed an additional set of slides in this group, and found a correlation between FISH and automated IA scores. We conclude that automated image analysis is sensitive to small differences in protein expression, has a wide dynamic range, and provides data superior to conventional by-eye scoring. In undecided cases HER-2 protein expression correlates with FISH data; therefore ultimately IA of HER-2 protein expression alone may provide a basis for clinical decisions. [Table: see text]
Adjuvant chest wall and nodal irradiation: maximize cure, minimize late cardiac toxicity.
Authors: R R Kuske
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.8.2579 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9704706 Adjuvant chest wall and nodal irradiation: maximize cure, minimize late cardiac toxicity. R R KuskexR R KuskeSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.8.2579 First Page PDF © 1998 by American Society of Clinical Oncology
Comparison of the beta-like globin gene families of rabbits and humans indicates that the gene cluster 5'-epsilon-gamma-delta-beta-3' predates the mammalian radiation.
Authors: R C Hardison
Journal: Molecular Biology and Evolution (1984)

The members of the rabbit and human beta-like globin gene families have been compared both by a computer-generated dot matrix graphical analysis of each entire gene and by calculating divergences in the coding regions. The rabbit-human gene pairs beta 4-epsilon, beta 3-gamma, psi beta 2-delta, and beta 1-beta were identified as orthologous on the basis of sequence similarities found in flanking and intervening sequences as well as by quantitative divergence calculations. The orthologous genes are in the same order on the chromosome in each species, which suggests that an ancestral family with the arrangement 5'-epsilon-gamma-delta-beta-3' preceded the mammalian radiation. Descendants of ancestral epsilon have diverged more slowly than other beta-like genes and are expressed only in embryonic life. Descendants of ancestral gamma and beta diverged at a higher rate and are expressed at wider range of developmental times. Descendants of delta have undergone nonreciprocal recombination at a high frequency and are often pseudogenes. Paralogous comparisons among the rabbit beta-like globin genes show that the beta 4-beta 3 and psi beta 2-beta 1 pairs are most similar and that beta 4 and beta 3 are more closely related to beta 1 than to psi beta 2. This fits with a branching pattern where the primordial beta split into ancestral epsilon/gamma and delta/beta genes, which later split into epsilon and gamma or delta and beta, respectively. Rabbit genes beta 4 and beta 1 acquired similar 3' untranslated regions after the epsilon/gamma split but prior to the mammalian radiation, presumably via a gene conversion event. The 5' end of beta 2 apparently converted with beta 1 after the radiation, and afterward it became a pseudogene.
Perspectives from man’s best friend: National Academy of Medicine’s Workshop on Comparative Oncology
Authors: Amy K. LeBlanc, Matthew Breen, Peter Choyke, Mark Dewhirst, Timothy M. Fan, Daniel L. Gustafson, Lee J. Helman, Michael B. Kastan, Deborah W. Knapp, Wendy J. Levin, Cheryl London, Nicola Mason, Christina Mazcko, Patricia N. Olson, Rodney Page, Beverly A. Teicher, Douglas H. Thamm, Jeffrey M. Trent, David M. Vail, Chand Khanna
Journal: Science Translational Medicine (2016)

Scientists gather to survey comparative oncology research and pinpoint potential contributions to human therapeutics.
PTH-227 Early post-natal environment and supplementation of b. lactis ncc2818 exert a sustained influence on the developing immune system and on gut microbial co-metabolism in the pig
Authors: CA Merrifield, MC Lewis, B Berger, O Cloarec, F Charton, L Krause, S Duncker, A Mercenier, E Holmes, M Bailey, JK Nicholson
Journal: Gut (2015)

<h3>Introduction</h3> The young piglet is a valuable model for human infants in studies designed to identify interactions between the developing immune system, metabolism and the microbiome in early life. The early postnatal environment, including factors such as weaning and acquisition of the gut microbiota, has been causally linked to the development of later immunological diseases such as allergy and autoimmunity. Here, we show that early-life environment influences development of metabolic and immune phenotype as well as the gut microbiota in a porcine model. <h3>Method</h3> Piglets were removed to an isolator facility 24 h after birth, formula fed until 21d at which point they were weaned. Animals were gender and litter-matched to the control group or supplemented with the human probiotic<i>Bifidobacterium lactis </i>NCC2818 from 1d. Animals were sacrificed at 35d and the experiment was repeated with a second batch of piglets under identical husbandry conditions. Metabolic profiling of serum and urine at 35d was carried out using <sup>1</sup>H Nuclear Magnetic Resonance spectroscopy (NMR). Intestinal barrier function was assessed using immunofluorescence histology and immunoglobulin and cytokine production from various immunological sites was quantified. 16s pyrosequencing was conducted on colonic content and mucosal scrapings. <h3>Results</h3> The immediate environment during the first 24 h of life influenced the early microbiota, with animals from different batches having significantly different colonic bacteria and urinary metabolic profiles at 35d. Despite the underlying differences between the experimental batches, the administration of <i>Bifidobacterium lactis</i>NCC2818 in the diet significantly affected the metabolic phenotype, mucosal cytokine and immunogobulin production, and increased expression of intestinal tight cell junction proteins. Importantly, changes in composition of the microbiota were insufficient to explain the effect of the probiotic on these parameters. <h3>Conclusion</h3> We demonstrate that the environment during the first day of life influences development of the microbiota, metabolic phenotype and immune parameters and suggest that nutritional intervention at this early stage of life could be beneficial for at-risk infants who have suffered aberrant initial intestinal colonisation caused by, for example, caesarean or premature birth. <h3>Disclosure of interest</h3> None Declared.
Phase I clinical trial of adoptive cellular immunotherapy with APN401 in patients with solid tumors
Authors: Pierre Triozzi, Mitra Kooshki, Angela Alistar, Rhonda Bitting, Amy Neal, Guenther Lametschwandtner, Hans Loibner
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Casitas-B-lineage lymphoma protein-b (Cbl-b), an E3 ubiquitin ligase, has been identified as a key intracellular checkpoint limiting lymphocyte activation. Inhibiting Cbl-b has been shown to enhance T cell and natural killer cell mediated antitumor activity in mouse tumor models.
The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate.
Authors: W R Crom, C B Pratt, A A Green, J E Champion, D B Crom, C F Stewart, W E Evans
Journal: Journal of Clinical Oncology (1984)

The pharmacokinetics of high-dose methotrexate (MTX, 5-15 g/m2) were evaluated in 11 children and adolescents who had previously received two to eight doses of cisplatin (90 mg/m2) in the treatment of malignant solid tumors. The half-life for disappearance of MTX from serum during the first 24 hours after infusion was determined from serum samples obtained at the end of a six-hour infusion and six, 12, and 24 hours after infusion. These values were compared to a mean half-life of 2.83 (+/- 0.34) hours following 489 courses administered to 71 patients who had not received cisplatin. Stepwise multiple linear regression analysis of patient variables revealed cumulative cisplatin dosage and time from last cisplatin dose as the best predictors of MTX half-life (r2 = 65.4%, p less than 0.001). The best predictors of 24-hour serum concentration were cumulative cisplatin dosage and MTX dosage (r2 = 54.2%, p less than 0.001) in the multiple linear regression model. Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity. Patients receiving up to 270 mg/m2 of cisplatin appear to have minimal increases in MTX half-life, while the likelihood of delayed clearance increases in patients who have received 360 mg/m2 or more of cisplatin. All patients who have previously received cisplatin should be treated cautiously with high-dose MTX and prospective pharmacokinetic monitoring should be routinely performed.
Validation of history on atopy and childhood illness in a clinical birth cohort study
Authors: Nadja Hawwa Vissing, Signe Marie Jensen, Hans Bisgaard
Journal: European Respiratory Journal (2011)

Background:  The longitudinal birth cohort study is the preferred design for studies of childhood health, particularly asthma and other atopic diseases. Still, prospective data collection depends on recollection of the medical history representing a potential recall-bias.   Aims:  We aimed to ascertain completeness of our data on atopic disease and other health symptoms reported in a closely monitored birth cohort study. Possible bias from symptom severity and socioeconomics were sought.   Methods:  The Copenhagen study on Asthma in Childhood (COPSAC) is a clinical birth cohort study of 411 children. Child health is monitored at 6-montly clinic visits from birth till age 3 with a particular emphasis on asthma and other atopic diseases. Cohort information of 260 children was compared with the records from family practitioner as an external reference.   Results:  A total of 6134 medical events were reported at the COPSAC interviews. Additional 586 medical events were recorded by family practitioners, but not reported at the interview. None of these missed events were related to atopic disease. Respiratory, infectious and skin related symptoms showed completeness above 90%, other diseases showed lower completeness around 77%. There was no meaningful influence from concurrent asthma or socioeconomics, including household income, mother9s education or employment.   Conclusion:  The COPSAC study exhibited full completeness to the main study objectives, atopic disease, and high completeness to respiratory, infectious and skin related illness. Our findings support the validity of clinical interviews of parents in longitudinal cohort studies investigating childhood illness and atopic disease in childhood.