tbuckley/cabot-search huggingface dataset:
Abstract 4581: Implementation of a new cancer protein biomarker development pipeline - NCI's clinical proteomic technologies for cancer
Authors: Chris Kinsinger, Mehdi Mesri, Emily Boja, Tara Hiltke, Amir Rahbar, Robert Rivers, Henry Rodriguez
Journal: Cancer Research (2010)

Abstract Proteomic technologies have revolutionized the area of protein biomarker discovery by providing powerful new tools such as protein arrays and mass spectrometry to characterize complex proteomes, multi-protein complexes and post-translational modifications. However, attempts to use proteomic approaches to discover cancer biomarkers in biofluids and tissues have been largely unsuccessful in the past. This indicates issues present in the biomarker candidate pipeline mainly due to variability within biomarker discovery and the lack of verification (or pre-validation) of biomarkers prior to costly clinical validation studies using immunosorbent assay (ELISA). Clinical Proteomic Technologies for Cancer (CPTC) initiative established by NCI in 2006 sought to develop a more refined, efficient, and reliable biomarker development pipeline anticipated to produce better-credentialed candidate leads, ultimately accelerating the translation of new cancer biomarkers into diagnostic tests. CPTC is a team science based five-year initiative composed of three components with an emphasis on the optimization of technology platforms, standards development, involvement with the U.S. Food and Drug Administration, and community reagents and resources development to address the challenges of clinical proteomics and to enhance technical abilities to identify and measure proteins accurately, quantitatively and reproducibly in biological systems. This presentation highlights the significant milestones of this initiative in building a more reliable and efficient protein biomarker development pipeline - one that consists of three development stages that we believe places the field of proteomics as a key component in initiatives for personalized medicine - Discovery, Verification, and Validation. 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 4581.
Abstract 1858: Estrogen receptor beta as a tractable therapeutic target
Authors: Carly S. Filgueira, Cindy Benod, Xiaohua Lou, Anders Strom, Jan-Åke Gustafsson, Anders Berkenstam, Paul Webb
Journal: Cancer Research (2015)

Abstract Nuclear receptors (NRs) regulate a variety of biological processes and are critically important in the emergence, prevention, and treatment of cancers. Many NRs represent well-validated drug targets as their ligands are used extensively in medicine. However, there still remains an active search for novel agonists and antagonists with enhanced selectivity. Estrogen receptor β (ERβ) is an attractive target for drug development. It plays different roles in gene expression from ERα, implicated in breast and uterine cancers, and displays overlapping but distinctive tissue distributions from ERα and non-redundant roles. Further, emerging evidence indicates that ERβ plays anti-proliferative and anti-apoptotic roles in a variety of cancers. These considerations have led to the suggestion that ERβ is an appealing tractable target for development of selective agonists to treat and prevent colon, breast, prostate, lung, and skin cancer and natural and synthetic estrogens for ERβ are being studied in colon, breast, and lung cancers. However, because of the high sequence similarities between ERα and ERβ, preferentially targeting one subtype can prove challenging. Repositioning of existing approved drugs with known side effect profiles can provide advantages because de novo drug design suffers from high developmental failure rates and undesirable side effects which have dramatically increased costs. Our research strategy is to identify and develop an ERβ agonist lead compound by using a systematic step-wise hit-to-lead campaign. We have identified a series of ERβ-selective lead compounds derived from screening libraries of clinically relevant compounds and have shown that some of these compounds display interesting and desirable selective modulator activities. Citation Format: Carly S. Filgueira, Cindy Benod, Xiaohua Lou, Anders Strom, Jan-Åke Gustafsson, Anders Berkenstam, Paul Webb. Estrogen receptor beta as a tractable therapeutic target. [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 1858. doi:10.1158/1538-7445.AM2015-1858
THE NEGATIVE EFFECTS OF PERIOPERATIVE BLOOD TRANSFUSIONS MAY BE MITIGATED WHEN PERFORMING CORONARY ARTERY BYPASS GRAFTING OFF-PUMP
Authors: Juan B. Grau, Christopher K. Johnson, Cyrus E. Kuschner, Giovanni Ferrari, Richard E. Shaw, Mariano Brizzio, Michael Kesselbrenner, Alex Zapolanski
Journal: Journal of the American College of Cardiology (2015)
The Combination of 13N-Ammonia and 18F-FDG in Predicting Primary Central Nervous System Lymphomas in Immunocompetent Patients
Authors: Xinchong Shi, Xiangsong Zhang, Chang Yi, Xiaoyan Wang, Zhifeng Chen, Bing Zhang
Journal: Clinical Nuclear Medicine (2013)

Accurate identification of primary central nervous system lymphoma (PCNSL) and its differentiation from other brain tumors remain difficult but are essential for treatment. In this study, we investigated whether (13)N-ammonia combined with (18)F-FDG could distinguish PCNSL from solid gliomas effectively.Ten consecutive patients with final diagnosis of PCNSL (5 female and 5 male patients; mean [SD] age, 59.10 [12.47] years; range, 43-74 years) and another fifteen consecutive patients with solid glioma lesions (5 female and 10 male patients; mean [SD] age, 46.73 [19.61] years; range, 14-72 years) were included in this study. PET/CT imaging was performed for all of them with both (18)F-FDG and (13)N-ammonia as tracers. Tumor-to-gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. Both Student t test and discriminant analysis were recruited to assess the differential efficacy of these 2 tracers.The T/G ratios of (18)F-FDG in PCNSL lesions were higher than in solid gliomas (3.26 [1.18] vs 1.56 [0.41], P < 0.001), whereas the T/G ratios of (13)N-ammonia in PCNSL lesions were lower than in solid gliomas significantly (1.38 [0.20] vs 2.11 [0.69], P < 0.001). All the lesions of PCNSL displayed higher T/G ratios of (18)F-FDG than (13)N-ammonia, whereas 14 (77.8%) of 18 glioma lesions showed contrary results. Tumor classification by means of canonical discriminant analysis yielded an overall accuracy of 96.9%, and only one glioma lesion was misclassified into the PCNSL group.PCNSLs and solid gliomas have different metabolic profiles on N-ammonia and F-FDG imaging. The combination of these 2 tracers can distinguish these 2 clinical entities effectively and make an accurate prediction of PCNSL.
Abstract 5473: Integrative approach towards the functionality of CIAO1 gene
Authors: Mau-Ting Lin, Donna G. Albertson
Journal: Cancer Research (2012)

Abstract Previous genome-wide analysis of copy number aberrations in oral squamous cell carcinoma (SCC) and oral epithelial dysplasia, a pre-malignant lesion, by array CGH has revealed that the genomes of these cancers and pre-cancers frequently harbor narrow (∼3Mb) regions of amplification on chromosome 2q11 region. Overexpression of CIAO1, a putative cytosolic iron-sulfur protein within this region, has been observed in patients’ cancerous samples and oral SCC lines. Knockdown of CIAO1 protein by RNAi results in growth retardation in oral SCC lines. Therefore, three HaCaT cell clones with an inducible Tet-on CIAO1 gene have been established to unravel the nature of the CIAO1 signaling network. Through the triangulation of protein-protein interactions, quantitative PCR array and transcription factor reporter array, we have investigated the early effects of CIAO1 overexpression in immortalized HaCaT cells, which may add to the understanding of oral cancer tumorigenesis. 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 5473. doi:1538-7445.AM2012-5473
Renal Pathology with Clinical and Functional Correlations.
Journal: Annals of Internal Medicine (1990)

This important reference has been brought as up-to-date as possible, with more than one-third of the chapters completely rewritten. Renal Pathology, Second Edition is edited by specialists in renal medicine and pathology and distinguished by an emphasis on correlating pathology to clinical findings. Covers normal renal structure and function and the clinical patterns of functional disturbances due to immunologic, infectious, vascular and metabolic causes. Helps the reader analyze renal biopsy specimens and define and categorize renal structural injury at its earliest stages. New in the second edition: new chapters on AIDS, renal tuberculosis, immunotactoid glomerulopathy, and malignancies and secondary development. Also included are 24 new color illustrations
Developing Primary Care The Academic Contribution: The Conference of Academic Organizations in General Practice, by Ed D J Pereira Gray
Authors: C. van Wee
Journal: BMJ (1997)

Ed D J Pereira Gray Royal College of General Practitioners, £9.90, pp 59. ISBN 0 85084 227 1

Shifting to a health service led by primary care entails many changes to the working environment of general practitioners. Developing Primary Care provides a detailed review of what it will mean for the academic aspects of general practice: research, development, teaching, and training.

The report summarises general practice's impressive track record in each of these areas. For example, the teaching model …
Colon Visualization on Bone Scan
Authors: YUH-FENG WANG, SHIOU-CHI CHERNG, CHENG-YI CHENG, HUENG-YUAN SHEN, WEN-SHENG HUANG
Journal: Clinical Nuclear Medicine (1998)

Several causes of bowel visualization on bone scintigraphy have been discussed. Tc-99m MDP whole-body bone imaging was performed on a 38-year-old woman for clinical staging of breast cancer. The bone scintigraphy demonstrated no skeletal abnormality. However, extensive accumulation of radioactivity in the colon was noted. This resulted from the patient drinking her own urine, because some people believe that it is a way to improve their health. To avoid such misleading conditions, thorough history taking, including administration of traditional remedies, special habits, and the habitat of the patient, are necessary before imaging.
PTU-064 Pre-liver transplant biopsy in hepatocellular carcinoma: a potential exclusion criterion for transplantation?
Authors: R Young, M Aldiwani, A Hakeem, A Nair, J Wyatt, G Toogood, P Lodge, R Jones, R Prasad
Journal: Gut (2012)

<h3>Introduction</h3> In cirrhotic patients with hepatocellular carcinoma (HCC) pre-liver transplant (LT) staging biopsy of the largest tumour is undertaken in some centres. Proponents advocate that poor differentiation confers such poor prognostic significance that it can be used as an exclusion criterion for LT, resigning patients to palliative treatments. We do not carry out staging biopsies and sought to interrogate its potential use and impact on our practice in the context of ever increasing demands for organs. <h3>Methods</h3> 65 consecutive patients undergoing orthotopic LT for radiologically diagnosed HCC at St James9s University Hospital between 2006 and 2011 were identified for analysis from a prospectively maintained database. All patients had cirrhosis and incidental tumours were excluded. Diagnosis was in accordance to published guidelines and various clinic-pathological parameters were recorded. MRI findings were correlated with explant histological examination. Median follow-up was 24 months. Student t test, Mann–Whitney U test or related samples Wilcoxon Signed Rank tests were used where appropriate. The Kaplan–Meier method was used to determine survival with Log-Rank and Cox stepwise regression for survival comparisons. p&lt;0.05 was considered to be statistically significant. <h3>Results</h3> 3 year survival was 81% with the only independent predictor microvascular invasion (p=0.019). In 5 (7.7%) patients there was no HCC in the explant. A discrepancy between the definition of the largest lesion on pre-LT radiology and the largest explant tumour occurred in 5 (7.7%) cases. Tumours were classified as well, moderately or poorly differentiated in 39 (30.2%), 66 (51.2%) and 24 (18.6%) cases. In patients with multifocal HCC, 9 (34.6%) had tumours of differing grades. In two (7.7%) patients the largest tumour was well differentiated while smaller tumours in the explant were poorly differentiated. In one patient the largest lesion was benign with other smaller invasive carcinomas confirmed histologically. <h3>Conclusion</h3> There is a need to optimise LT selection strategies for HCC. Microvascular invasion was the only independent predictor of outcome and the challenge of predicting it pre-operatively remains. Crucially, the largest lesion was not always representative of overall tumour burden or biological aggression and its potential use to exclude patients from curative treatment is questionable. <h3>Competing interests</h3> None declared.
Calcineurin inhibitor therapy-associated esophageal polyps 12 years after heart transplantation
Authors: C. Langner, A. Eherer, M. Vieth
Journal: Endoscopy (2011)

Drug-induced injury of the gastrointestinal tract is increasingly common but generally under-recognized. Within the esophagus, abnormalities are commonly referred to as “nonspecific pill esophagitis”, characterized by erosions, ulcers or occasionally strictures. Alendronate, doxycycline, and potassium chloride have been identified as potential causes [1].
Abstract 1609: In vivo and ex vivo comparison of two human AML bone marrow engraftment mouse models using fire fly luciferase expressing MOLM-13 and MV4-11 cells
Authors: Andreas Lingnau, Daniel Feger, Steffen Hoffmann, Sarah Umber, Michael HG Kubbutat
Journal: Cancer Research (2011)

Abstract Acute myeloid leukemia (AML) is the most common leukemia affecting adults. In 70-90% of all AML patients FLT3, a receptor tyrosine kinase which plays an important role in normal hematopoiesis, is highly expressed. Furthermore, in about 30% of all AML patients activating internal tandem duplications (ITDs) or point mutations within the FLT3 gene have been identified. FLT3, therefore, is one of the most promising drug targets for the treatment of AML. Most often novel FLT3 protein kinase inhibitors are tested in subcutaneous xenograft mouse models using various human AML cell lines. To generate more relevant, orthotopic AML in vivo models, we stably transduced the human AML cell lines MOLM-13 and MV4-11 with fire fly luciferase (MOLM-13-Luci and MV4-11-Luci) suitable for in vivo bioluminescence imaging. MOLM-13 carries a heterozygous and MV4-11 a homozygous FLT3 internal tandem duplication (ITD) mutation. In vivo growth of MOLM-13-Luci and MV4-11-Luci cells after subcutaneous implantation in NMRI nude mice proofed that stable expression of luciferase did not alter growth characteristics of these cells. To initiate orthotopic growth, both AML cell lines were implanted intravenously via the tail vein into NOD SCID mice after Cyclophosphamide treatment. Cyclophosphamide facilitates engraftment of the human cells by reducing the endogenous bone marrow cell population. Approximately two (MOLM-13-Luci), or three (MV4-11-Luci) weeks after implantation, luciferase activity was detectable in the pelvic region of the mice indicating growth of both tumor cell lines. Within the next weeks luciferase activity was also seen in additional parts of the mouse at different levels. After necropsy a set of different organs and tissues was analysed ex vivo for luciferase activity. The pattern of metastasising tumor cells was compared in both models. Furthermore, detection of human Ki-67 protein using appropriate human specific antibodies allowed verification of growth of MOLM-13-Luci and MV4-11-Luci cells in different tissues. Sutent, a small-molecule kinase inhibitor, totally abolished tumor growth of both orthotopically growing tumors, indicating that both in vivo models are highly suitable for the characterisation of novel drugs directed against AML. 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 1609. doi:10.1158/1538-7445.AM2011-1609
Quantitative assessment of the behavior of psychotherapy supervisors
Authors: S B Shanfield, P C Mohl, K L Matthews, V Hetherly
Journal: American Journal of Psychiatry (1992)

The aim of this study was to explore the behavior of psychotherapy supervisors by using the Psychotherapy Supervision Inventory.The authors used the Psychotherapy Supervision Inventory to rate 53 videotaped supervision sessions of 34 different supervisors. They also used the variable of the rater's perception of the excellence of the supervisor as a teacher. The data were subjected to a cluster analysis and a K-means analysis. Discriminant function analyses were applied to the comparison of the behavior of 19 supervisors with two different residents and the behavior of all 34 supervisors with residents in three different years of training. The relationship between rater-perceived excellence and Psychotherapy Supervision Inventory scores was analyzed by using stepwise multiple regression.There was a high level of agreement among the four raters' judgments of supervisors' excellence. Empathy accounted for 72% of the variance in rater-perceived excellence and focus on the therapist accounted for an additional 5%. When empathy was dropped from the equation, experiential orientation accounted for 60% of the variance in ratings of excellence, clarification and interpretation accounted for an additional 16%, and depth accounted for another 3%.In the context of established relationships, supervisors have stable behavior patterns. Rater-perceived excellence is related to the supervisor's focusing on the resident's immediate experiences and making many synthesizing comments in depth. The Psychotherapy Supervision Inventory can be used to orient supervisors to supervision and provide feedback about their behavior.
Treatment of Primary Breast Cancer with Chemotherapy and Tamoxifen
Authors: Bernard Fisher, Carol Redmond, Ann Brown, Norman Wolmark, James Wittliff, Edwin R. Fisher, David Plotkin, David Bowman, Sidney Sachs, Janet Wolter, Robert Frelick, Richard Desser, Nicholas LiCalzi, Peter Geggie, Thomas Campbell, E. George Elias, David Prager, Paul Koontz, Herbert Volk, Nikolay Dimitrov, Bernard Gardner, Harvey Lerner, Henry Shibata
Journal: New England Journal of Medicine (1981)

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were ≥10 fmol. Among patients ≥50 years old treatment failure was significantly reduced (P<0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients ≤49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients ≤49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients ≥50 years old whose levels are low. (N Engl J Med. 1981; 305:1–6.)
Dissecting Aneurysms of the Coronary Artery
Authors: Gerald L. Brody, John F. Burton, Edward S. Zawadzki, A. James French
Journal: New England Journal of Medicine (1965)

ANEURYSMS of the coronary arteries are decidedly uncommon. They comprise congenital, mycoticembolic, syphilitic, polyarteritis-nodosa, arteriosclerotic and dissecting types. Of these, arteriosclerotic aneurysms and those resulting from polyarteritis nodosa are the most common whereas dissecting aneurysms are very rare. In 1962 two of us1 reported a case of such an aneurysm in a thirty-five-year-old mother who died unexpectedly six weeks post partum. Since that time 3 more cases very like the first have been obtained. In addition there is a dissimilar case, that of a forty-nine-year-old woman who died seven days after a segmentectomy of the left lower pulmonary lobe for . . .
Abstract P1-07-06: Effect of biospecimen variables on proteomic biomarker assessment in breast cancer
Authors: F Meric-Bernstam, A Akcakanat, H Chen, A Sahin, E Tarco, S Carkaci, B Adrada, G Singh, K Anh-Do, Z Garces, EA Mittendorf, G Babiera, J Wagner, I Bedrosian, S Krishnamurthy, WF Symmans, AM Gonzalez-Angulo, G Mills
Journal: Cancer Research (2012)

Abstract Background: PI3K/Akt/mTOR signaling is being actively pursued as a therapeutic target. We sought to determine how tumor heterogeneity and biospecimen variables affect assessment of PI3K/Akt/mTOR pathway activation. Methods: Intraoperative image-guided core-needle biopsies (CNB) of primary breast tumors were prospectively collected in 53 patients with invasive breast cancer. After surgery, specimens were collected from the center and periphery of the excised tumor. CNB, central and peripheral surgical specimens were assessed with reverse phase proteomic arrays (RPPA), H&amp;E and immunohistochemistry (IHC). Results: The expression of standard of care markers ER, PR, and HER2 by RPPA correlated well between biospecimen types. Overall, there was a significant correlation between the expression of 132 (86%) of 154 different markers in the center and periphery; the correlation was significantly higher for smaller tumors, and with shorter cold ischemia time. Expression of many investigational prognostic markers and druggable targets on CNB correlated with expression in the surgical specimen (average of center and periphery), while others, such as EGFR and c-MET, had a weak correlation. Of 154 RPPA markers, 132 (86%) were not statistically different between the center and periphery, and 97 (67%) were not different between the CNB and the surgical specimen. On analysis of the PI3K/AKT/mTOR pathway, pAkt S473 and PTEN had a significant correlation between central and peripheral specimens, and between CNB and surgical specimens. However, pAkt S473, pS6 S235/236 and pS6 240/244 levels were higher in CNB than the central specimens both by RPPA and by IHC. When patients were classified by RPPA PI3K pathway activation score, there was a moderate agreement between classification on the CNB and central specimens (Cohen's Kappa 0.539). However 9 of 20 tumors classified as having PI3K activation on CNB were classified as not having pathway activation on central specimens. Conclusions: There is remarkable homogeneity in expression of biomarkers within a tumor. However, proteomic markers are differentially expressed by biospecimen type and other preanalytic variables. PI3K pathway activation is greater in CNB compared to surgical samples. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-06.