tbuckley/cabot-search huggingface dataset:
Abstract P2-11-07: Mutually exclusive expression pattern of the immune co-inhibitory molecules B7-H4 and PD-L1 in triple negative breast cancer
Authors: DR Shaffer, K Nagashima, V Cortez-Retamozo, I Feldman, J Smith, M Zafari, R Larson, R Mabry, T Novorantseva, M Briskin, S Sathyanaryananan
Journal: Cancer Research (2016)

Abstract B7-H4 (VTCN1, B7x, B7S1) is a transmembrane protein belonging to the B7 family of costimulatory proteins and has been shown to inhibit T cell proliferation, cytokine secretion, and cytotoxic lymphocyte (CTL) induction. B7-H4 expressed on tumor cells or macrophages has been associated with poor prognosis and impaired T cell function in renal cell and ovarian cancers. Here we show B7-H4 is abundantly expressed in human breast cancer with triple negative breast cancer (TNBC) having the highest overall B7-H4 mRNA expression. We developed a specific and sensitive immunohistochemistry (IHC) assay for evaluation of B7-H4 protein and quantified B7-H4 expression in 156 breast tumor samples. Approximately 70% of the breast tumor samples had detectable B7-H4 expression whereas none of the normal or benign breast tissues stained positive for B7-H4. Multiplex IHC and flow cytometry studies showed that the majority of B7-H4 expression was restricted to the tumor epithelial cells, the CD45+ immune cells were negative for B7-H4 expression. Interestingly none of the TNBC samples that were positive for B7-H4 showed detectable expression of PD-L1 suggesting that B7-H4 and PD-L1 checkpoint proteins may act in a mutually exclusive manner. To evaluate the role of B7-H4 on tumor immune evasion, we overexpressed murine or human B7-H4 on the mouse colon-26 (CT26) tumor cell line and injected these cells intravenously into Balb/c mice. By day 14 we observed significantly more tumors as well as larger percent tumor area in the lungs of mice given CT26 cells transduced with human or mouse B7-H4 as compared to vector control transduced cells. These data suggest B7-H4 expression in tumors can accelerate tumor growth in immune competent mice and that targeting B7-H4 may provide therapeutic benefit. Given the mutually exclusive expression patterns of B7-H4 and PD-L1 a B7-H4 targeting agent may provide particular benefit in those patients where current anti-PD-1/PD-L1 therapies are not effective. Citation Format: Shaffer DR, Nagashima K, Cortez-Retamozo V, Feldman I, Smith J, Zafari M, Larson R, Mabry R, Novorantseva T, Briskin M, Sathyanaryananan S. Mutually exclusive expression pattern of the immune co-inhibitory molecules B7-H4 and PD-L1 in triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-07.
Novel tumor-inhibiting metal complexes: Preclinical efficacy and toxicity of the lanthanum(III) complex [tris(1,10-phenantroline)lanthanum]trithiocyanate FFC24
Authors: B. Kynast, N. Graf V. Keyserlingk, M. Hauses, P. Heffeter, M. Jakupec, P. Unfried, W. Berger, B. K. Keppler
Journal: Journal of Clinical Oncology (2004)

3166 Background: The search for new agents with favorable activity in different types of cancer revealed the novel lanthanide complex FFC24 with 1,10-phenatroline as ligand and lanthanum as central metal. This complex was chosen among different lanthanide complexes for further development due to its high activity in-vitro with a GI50 value of 1.28 μM and an activity profile and a mode of action being different compared to classical platinum drugs. Methods: FFC24 was examined in vivo concerning toxicity by determining the acute intravenous median lethal dose (LD50) and the no-observed-adverse-effect-level in the rat and in the mouse. The in-vivo efficacy screening of FFC24 was performed in the DLD-1 colon adenocarcinoma xenograft model in nude mice using intravenous application. Results: Examination of the acute intravenous toxicity in Sprague Dawley rats at a dose level of 7.5, 15 or 17.5 mg/kg in 0.9 saline revealed a LD50 of 21.60 mg/kg for all animals and 11.46 mg/kg for females only after extrapolation. The NOAEL was determined to be 7.5 mg/kg. In the mouse (outbred albino), FFC24 was administered at doses of 10, 15 or 17 mg/kg and the LD50 was extrapolated to 62 mg/kg for females and males together and 26.6 for males alone. The NOAEL in the mouse was 10 mg/kg. The in-vivo efficacy testing in the DDL-1 xenograft model in comparison to MTX and CisPt was performed at 4, 8, or 12 mg/kg on days 0, 1, 2, 3 and 4 (qd5). The anti-tumor activity of FFC24 in terms of relative tumor volume doubling time respectively growth delay was comparable to CisPt and MTX without any signs of toxicity. Only slight differences concerning activity with respect to the administered dose of FFC24 were observed. Conclusions: With FFC24 a new, very promising non-platinum anti-tumor agent with a different profile of activity and a new mode of action has entered the preclinical development. No significant financial relationships to disclose.
Effects of <i>BRCA1/2</i> on Ovarian and Breast Cancer Survival—Response
Authors: Qian Zhong, Hong-Ling Peng, Xia Zhao, Lin Zhang, Wei-Ting Hwang
Journal: Clinical Cancer Research (2015)

We thank Gong and colleagues (1) for their thoughtful comments and interest in our meta-analysis of the effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival (2).Regarding the first point, we want to point out one advantage of using hazard ratio (HR) as an overall measure of association is that HR is irrelevant to a specific time point (e.g., 5 or 10 years), because HR estimates the true ratio of two underlying hazards and the ratio is assumed to be constant over time. Varying follow-up durations may potentially influence the width of the confidence interval (CI), which is already factored into the calculation of the combined HR. We had repeated the meta-analysis using the 10-year HR estimate from McLaughlin and colleagues (3) instead of the 5-year HR and obtained almost identical results. Meta-analysis does not require studies to have comparable follow-up. We believe that our combined HR as an overall measure of association remains valid.Regarding the second point, the P value of 0.008 reported in Boyd and colleagues (4) was based on a log-rank (Cox–Mantel) test, so theoretically their results could be different from results estimated by a Cox PH model if the underlying hazard functions are not entirely proportional to each other, as suggested by Fig. 2 (4). The technique of estimating HR by reading KM curve directly performs well if there are a sufficient number of subjects and events and if the observation intervals are adequate (5), such as in that study.On the third point, we wanted to avoid a laundry list of subgroup analysis of all possible scenarios; thus, we had chosen to focus our subgroup analysis on patient, tumor, and treatment characteristics that we believed matter the most in terms of their prognostic values. In addition, statistical theory has shown that estimation of HR and its validity does not depend on whether the study is done prospectively or retrospectively.The numbers in Fig. 2 were slightly off from the original publications because of the algorithm used in RevMan software. RevMan computes a symmetric CI for log(HR) because they are supposed to be constructed based on a (symmetric) normal distribution. If the original CI reported is not perfectly symmetric (on a log scale), then there will be a slight discrepancy. Rounding can also contribute to this. Additional information can be found on the Revman manual for the statistical method and algorithm (6).See the original Letter to the Editor, p. 3806No potential conflicts of interest were disclosed.
High detection rates do not necessarily lead to lower mortality
Authors: S. Bhargava, D J Watmough, F. Syed, A. Mernon, F. Gharbawy
Journal: BMJ (1996)

EDITOR,—The finding of a substantially higher rate of detection of breast cancer by two view compared with single view x ray mammography in the well designed randomised clinical trial by Nicholas Wald and colleagues deserves comment.1 The assumption in the authors' four key messages that high detection rates will lead to larger reductions in mortality from breast cancer is not borne out by evidence from the randomised controlled trials summarised by Fletcher et al.2 The Health Insurance Plan trial detected 2.7 cancers, the …
Diagnosis of<i>Pneumocystis carinii</i>Pneumonia: Improved Detection in Sputum with Use of Monoclonal Antibodies
Authors: J A Kovacs, V L Ng, H Masur, G Leoung, W K Hadley, G Evans, H C Lane, F P Ognibene, J Shelhamer, J E Parrillo
Journal: New England Journal of Medicine (1988)

With the dramatic increase in the frequency of Pneumocystis carinii pneumonia associated with human immunodeficiency virus infection, there has been a need for more rapid and less invasive diagnostic techniques. Recent studies have shown that examination of induced sputum can establish the diagnosis of P. carinii pneumonia in about 55 percent of cases. To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive than Giemsa or toluidine blue O stains in detecting P. carinii in sputum, we undertook two prospective studies. Of 63 patients at one institution from whom sputum specimens were obtained, 49 were ultimately given a diagnosis of P. carinii pneumonia, 46 of them by staining of sputum. The sensitivity of the three stains in detecting P. carinii was 45 of 49 (92 percent) for immunofluorescence; 37 of 49 (76 percent) for Diff-Quik (a Giemsa-type stain); and 39 of 49 (80 percent) for toluidine blue O. There were no false positive immunofluorescent stains. In a similar study of a series of 25 patients at another institution, a diagnosis of P. carinii pneumonia was made in 23 of 25 patients by staining of induced sputum. We conclude that examination of induced sputum is a rapid, sensitive, and inexpensive method for diagnosing P. carinii pneumonia and that indirect immunofluorescence is a practical and highly sensitive staining technique for establishing this diagnosis.
Plasma Triglyceride Level and Mortality from Coronary Heart Disease
Authors: Michael H. Criqui, Gerardo Heiss, Richard Cohn, Linda D. Cowan, Chirayath M. Suchindran, Shrikant Bangdiwala, Steven Kritchevsky, David R. Jacobs, Haesook Kim O'Grady, C.E. Davis
Journal: New England Journal of Medicine (1993)

Whether the plasma triglyceride level is a risk factor for coronary heart disease has been controversial, and evaluation of the triglyceride level as a risk factor is fraught with methodologic difficulties.We studied the association between plasma triglyceride levels and the 12-year incidence of death from coronary heart disease in 10 North American populations participating in the Lipid Research Clinics Follow-up Study, while adjusting for the potential confounding effects of other risk factors for cardiovascular disease, including the level of high-density lipoprotein (HDL) cholesterol. All analyses were sex-specific, and separate analyses were performed in high and low strata of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, fasting plasma glucose, and age.The rates of coronary death in both men and women increased with the triglyceride level. In Cox proportional-hazards models adjusted for age, in which the natural log of the triglyceride levels was used to give a normal distribution, the relative risk per natural-log unit of triglyceride (e.g., a triglyceride level of 150 mg per deciliter vs. a level of 55 mg per deciliter) was 1.54 (95 percent confidence interval, 1.19 to 1.98; P < 0.001) in men and 1.88 (95 percent confidence interval, 1.19 to 2.98; P < 0.007) in women. After an adjustment for potential covariates, however, these relative risks were not statistically significant. Analyses based on lipoprotein cholesterol levels revealed a positive association between the triglyceride level and coronary mortality in the lower stratum of both HDL and LDL cholesterol, but not in the higher stratum. Conversely, the HDL cholesterol level was unrelated to coronary mortality in the lower stratum of LDL cholesterol, but was strongly inversely associated with coronary death in the higher stratum of LDL cholesterol. The relative risk of coronary death associated with triglyceride level was higher at younger ages. The associations between the triglyceride level and coronary mortality in the lower HDL cholesterol, LDL cholesterol, and age strata were small and were further reduced by an adjustment for the fasting plasma glucose level.Overall, the plasma triglyceride level showed no independent association with coronary mortality. However, in subgroups of subjects with lower HDL and LDL cholesterol levels and in younger subjects, defined a priori, an association between the triglyceride level and coronary mortality was observed, although this association was small and was not statistically significant after an adjustment for the plasma glucose level.
Evaluation of Neonatal-Intensive-Care Programs
Authors: John C. Sinclair, George W. Torrance, Michael H. Boyle, Sargent P. Horwood, Saroj Saigal, David L. Sackett
Journal: New England Journal of Medicine (1981)

Within the past 15 years, regional neonatal-intensive-care programs have been introduced and have expanded rapidly. The efficacy of some of the individual interventions that constitute neonatal intensive care has been validated in randomized, controlled clinical trials. It is therefore generally assumed that neonatal-intensive-care programs that incorporate these maneuvers are effective in reducing death and disability. However, the overall effectiveness of these programs has not been tested experimentally. Moreover, much of the non-experimental evidence supporting their value is based on the experience of referral units and does not measure the impact on the populations they serve. A definitive economic evaluation of neonatal intensive care has not yet been reported, despite the high cost of such programs. We conclude that neonatal-intensive care programs require further evaluation with rigorous scientific methods.
PARE0013 Demystifying Research Jargon: A Volunteer Led Glossary
Authors: R. Taylor, S. Blackburn, A. Higginbottom, C. Rhodes, K. Dziedzic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The terms and acronyms used in research can be confusing to lay people. This volunteer led project aimed to produce a plain language glossary of research terms and acronyms to assist the involvement of Research User Group members in research studies at a primary care research centre. <h3>Objectives</h3> To highlight how high quality glossaries for researchers and lay members can be produced by lay volunteers. <h3>Methods</h3> A member of the Research User Group (RUG) volunteered to lead the task of compiling a glossary of research terms and acronyms used in research protocols in studies of an Institute of Primary Care. The volunteer generated a list of research terms by a search of study information, discussion with RUG members and study coordinators. With support from the Institute9s Patient and Public Involvement team, lay definitions for the research terms were written by the volunteer using a combination of available resources (COCHRANE<sup>1</sup>, OMERACT<sup>2</sup>, INVOLVE<sup>3</sup>), web-based searches and creative thinking, and then compiled into a glossary. The glossaries were peer reviewed by Research User Group members and researchers. A glossary of generic research terms and individual study-specific glossaries were created <h3>Results</h3> A generic glossary and four study-specific glossaries were produced. The generic glossary contains lay definitions for 332 research terms. The RUG members and researchers described the glossaries as a useful reference to support peoples understanding of the research process. The glossaries are now being widely circulated throughout the Research Institute and externally. The volunteer described the work as a tedious process at times but he has developed new skills and obtained great pride and satisfaction at completing the task. <h3>Conclusions</h3> Research glossaries developed by lay volunteers can help Research User Groups better understand and support their contribution to the research process. The glossaries could be translated and made accessible in different formats. As well as sharing their experiences of a particular life experience, volunteers have many other skills and capabilities that can be harnessed to the benefit to the individual and the research team. <h3>References</h3> The Cochrane Collaboration. Glossary of Cochrane terms. http://www.cochrane.org/glossary OMERACT Patient Research Partners Group. OMERACT glossary for patient research partners. 2012. http://www.omeract.org/pdf/OMERACT11%20Glossary.pdf INVOLVE. Jargon Buster. http://www.invo.org.uk/resource-centre/useful-information/jargon-buster/ <h3>Acknowledgements</h3> We like to convey our gratitude to the Institute9s RUG members for their support and help to develop the research glossaries <h3>Disclosure of Interest</h3> None declared
Combination of irinotecan, oxaliplatin and cetuximab for patients with metastatic pancreatic cancer
Authors: M. Roach, F. Lee, I. Rabinowitz, G. Parasher, G. Heywood
Journal: Journal of Clinical Oncology (2006)

14135 Background: Gemcitabine-based chemotherapy is considered standard approach for patients with metastatic pancreatic cancer but the results remain unsatisfactory with survival averaging about 6 to 10 months. Cell line study indicates more than 90% of pancreatic cancer cells express EGFR receptor. We therefore explore the use of non-gemcitabine-containing regimen and add an EGFR inhibitor. Method: We initiated a regimen with irinotecan 120 mg/m 2 , oxaliplatin 85 mg/m 2 , and cetuximab 400 mg/m 2 first dose followed by 250 mg/m 2 for all subsequent doses delivered every 14 days for patients with metastatic pancreatic cancer. Results: From 1/2005 to 12/2005, a total of 5 patients were treated. Two males and three females, age 59 to 78. Three presented with metastatic disease. One had Whipple’s procedure then had disease recur 2 months post-surgery. One had locally advanced disease and progressed 10 months after concurrent chemoradiation. Grade III/IV neutropenia, anemia developed in 1/5 patients. Grade III/IV diarrhea and nausea/vomiting developed in 3/5 patients. Grade III/IV fatigue, anorexia developed in 4/5 patients. The non-hematologic toxicity was the main reason for dose reduction. 4 had CT scan for response evaluation. The fifth patient completed first cycle of treatment on 1/3/2006 and had CA19–9 dropped from 15,900 to 9,398 u/ml (40% decline). By CT scan, partial response rate is 75% as shown in the table. So far, two patients have died, 5 and 10 months since initiating treatment, one from recurrent hepatic abscess and one from fungus infection. Conclusions: This combination delivered every other week appears promising for patients with metastatic pancreatic cancer. The planned phase II trial will adopt a lower dose approach with irinotecan 90 mg/m 2 , oxaliplatin 60 mg/m 2 , and cetuximab 250 mg/m 2 . [Table: see text] No significant financial relationships to disclose.
Studies and Diagnostic Tests of Salivary-Gland and Thyroid-Gland Function with Radioiodine
Authors: Harry G. Thode, Charles H. Jaimet, Samuel Kirkwood
Journal: New England Journal of Medicine (1954)

RADIOIODINE (I131) has been used extensively in the diagnosis of thyroid disorders, and many tests have been developed.1 2 3 Most of these tests are based on two aspects of thyroid activity: the removal of iodine from the plasma and the synthesis and secretion of thyroxin.In clinical work on thyroid function in this laboratory both aspects of thyroid activity have been tested,4 the first by a thyroid pickup measurement, and the second by a measure of the fraction of radioiodine in the blood plasma that is protein bound, both tests being taken twenty-four hours after the administration of the dose. The . . .
Abstract 1430: Transcriptional regulatory loops among SNAI1, TWIST1, ZEB1, and ZEB2 defines the epithelial-mesenchymal transition (EMT) spectrum in epithelial ovarian cancer (EOC)
Authors: Ming Tan, Vin Yee Chuang, Tuan Zea Tan, Jean Paul Thiery, Ruby Yun-Ju Huang
Journal: Cancer Research (2015)

Abstract Epithelial-mesenchymal transition (EMT) refers to a sequential phenotypic transformation process from epithelial to mesenchymal states, which is well defined in embryonic development. During cancer progression, cancer cells undergo EMT progressively loss epithelial characteristics and gain mesenchymal properties and are correlated with acquisition of increased capacity of metastasis and resistance to chemo- and immunotherapy. Although EMT is intensively studied in various types of cancers, its role in epithelial ovarian cancer (EOC), the most lethal gynaecological malignancy in the world, has yet to be elucidated. Previously, our group proposed the concept of an EMT Spectrum which encompasses the hybrid “intermediate” phenotype as well as the bona-fide epithelial and mesenchymal phenotypes. EOC cells harboring intermediate phenotypes showed distinct functional differences in in vitro aggressiveness. We hypothesize that EMT transcriptional drivers, SNAI1, TWIST1, ZEB1, and ZEB2, contribute to different biological consequences and show different hierarchy to induce step-wise phenotypic changes along the EMT Spectrum. EMT models were established by overexpressing classic EMT drivers in selected EOC cell lines with different EM phenotypes at different positions of EMT spectrum to test the intrinsic transcriptional regulation networks. Quantitative PCR (QPCR) was performed to examine the cross regulation among the EMT transcriptional drivers and their downstream targets. There was no cross regulation detected in the most epithelial cell line, PEO1, while a simple, repressive regulatory net was found in the OVCA420 cell line. The cell line with an intermediate phenotype, OVCA429, showed a complex double positive feedback loop among the EMT drivers. The divergence in the transcriptional regulatory loops correlated with the differences of in vitro EMT functions. These results indicate that there is a dynamic EMT transcriptional regulatory network to further define the EMT spectrum. In conclusion, this study demonstrates that cancer cells with an intermediate phenotype are more easily to be pushed along the EMT spectrum due to their ability to initiate a complex transcriptional feedback regulatory loop. Citation Format: Ming Tan, Vin Yee Chuang, Tuan Zea Tan, Jean Paul Thiery, Ruby Yun-Ju Huang. Transcriptional regulatory loops among SNAI1, TWIST1, ZEB1, and ZEB2 defines the epithelial-mesenchymal transition (EMT) spectrum in epithelial ovarian cancer (EOC). [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 1430. doi:10.1158/1538-7445.AM2015-1430
The Genesis of Heart Sounds
Authors: Oscar Orias
Journal: New England Journal of Medicine (1949)

IT IS possible that the existence of the heart sounds was known to Hippocrates1 and even that he made use of his knowledge for diagnostic purposes, but William Harvey2 seems to have been the first to make specific reference to them: "With each movement of the heart as a quantity of blood is delivered from the veins to the arteries, a pulse takes place, which may be heard in the chest."It is rather astonishing that the physicians of that time had thus far paid no attention to the heart sounds, but it is even more astonishing that their existence, . . .