tbuckley/cabot-search huggingface dataset:
Abstract 3134: Integrin α6β4 upregulates EGFR ligands in pancreatic cancer cells
Authors: Brittany L. Carpenter, Min Chen, Kathleen L. O'Connor
Journal: Cancer Research (2012)

Abstract Because of late diagnosis and lack of effective treatments, pancreatic cancer is the 4th leading cause of cancer death in the US, with a death to incidence ratio that is nearly equal. In an effort to improve patient survival, there needs to be a focus on molecular mechanisms that confer a metastatic phenotype. The integrin α6β4 is overexpressed in pancreatic carcinoma and plays a role in cancer progression by promoting tumor invasion and metastasis as well as cell survival. We find that integrin α6β4 overexpression leads to upregulation of cancer promoting genes such as amphiregulin and epiregulin, ligands of the epidermal growth factor receptor (EGFR). The purpose of this study is to address how integrin α6β4 upregulates these ligands. We have identified large CpG islands within the amphiregulin and epiregulin promoters (-1500 to +500 bp from TSS) using CpG plot and CpG Island searcher. This provides a potential site for epigenetic modifications, which are essentially reversible, and therefore an ideal target for treatment. To test whether integrin α6β4 contributes to this regulation through DNA methylation pancreatic cancer cells expressing low levels of α6β4 were treated with DNA methyltransferase inhibitor 5-aza-2′deoxycitidine. Using Q-PCR, our results show that inhibition of DNA methyltransferase increases amphiregulin and epiregulin expression at the mRNA level. In contrast, when cells with high levels of integrin α6β4 were treated with the hypermethylating agent, S-adenosylmethionine, it leads to a decrease in amphiregulin and epiregulin expression. This implicates α6β4 as a regulator of this process allowing us insight into how this pathway might be regulated. Using ELISA, we also provide evidence that integrin α6β4 promotes increased autocrine secretion of amphiregulin after promoter demethylation. This is of particular interest to our lab because autocrine secretion of amphiregulin and epiregulin make it possible for cancer cells to both produce and respond to their own growth factors, promoting cellular invasion and metastasis. This study indicates that overexpression of integrin α6β4 in pancreatic cancer is associated with the hypomethylation of amphiregulin and epiregulin promoters, which may play an important role in the development of a malignant phenotype. 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 3134. doi:1538-7445.AM2012-3134
Ovarian cancer expression of ER, PgR, EGFR, and Her2 in Irish women may predict for targeted therapies: A single institution experience
Authors: K. I. Quintyne, M. Doyle, R. Landers, B. M. Cantwell
Journal: Journal of Clinical Oncology (2008)

22179 Background: To help select for targeted agents (e.g. erlotinib or trastuzumab), and to determine patients who would best benefit from hormonal manipulation, we estimated by immunohistochemistry (IHC), the expression of oestrogen-receptor (ER), progesterone-receptor (PgR), epidermal growthfactor receptor I (EGFR I) and c-erb-2 receptors (Her2; EGFR-2) in ovarian cancer tissue in Ireland. Methods: Tissue samples from 96 sequential patients with histologically proven ovarian cancer were studied. The receptors were determined by IHC using kits by DAKO - Denmark, Novocastra - UK, NeoMarkers Labvision - UK. ER and PgR stained slides were scored as strong, moderate, weak or negative, EGFR-1 was stained as either positive or negative and Her2 was scored either 0, 1+, 2+ or 3+. Any ER, PgR positivity, EGFR-1 positivity, and Her2 2+ and 3+ are reported. FISH analysis of Her2 2+ and 3+ samples was undertaken. Results: 96 patient samples were studied, mean age: 56 years (Range 19–82). Histology was either serous (53%) or mucinous (24%) in the majority. 60/96 (62%) were positive for at least 1 receptor, 29% were positive for 2 receptors, 4% were positive for 3 and 1% were positive for all 4. 21/96 (22%) were positive for ER/PgR. 13/96 (13%) were 2+ and 3+ for Her2. 20/96 (21%) were positive for EGFR-1, and 4/96 (4%) were positive for both EGFR I and Her2. Approximately 50% of 13 patient samples expressing 2+ and 3+ Her2 were poorly differentiated tumours, 33% of 21 EGFR positive tumours were poorly differentiated. Conclusions: Measurement of ER, PgR, EGFR-1 and Her2 receptor expression could lead to a rationale for using targeted agents (e.g. erlotinib, trastuzumab etc) and also endocrine therapies in ovarian cancer. Growth factor receptor expression may modulate response to targeted therapies and thus growth factor and hormone receptors should be determined in patients, allowing for more precise treatments. No significant financial relationships to disclose.
A Multidisciplinary Intervention to Prevent the Readmission of Elderly Patients with Congestive Heart Failure
Authors: Michael W. Rich, Valerie Beckham, Carol Wittenberg, Charles L. Leven, Kenneth E. Freedland, Robert M. Carney
Journal: New England Journal of Medicine (1995)

Congestive heart failure is the most common indication for admission to the hospital among older adults. Behavioral factors, such as poor compliance with treatment, frequently contribute to exacerbations of heart failure, a fact suggesting that many admissions could be prevented.We conducted a prospective, randomized trial of the effect of a nurse-directed, multidisciplinary intervention on rates of readmission within 90 days of hospital discharge, quality of life, and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet, social-service consultation and planning for an early discharge, a review of medications, and intensive follow-up.Survival for 90 days without readmission, the primary outcome measure, was achieved in 91 of the 142 patients in the treatment group, as compared with 75 of the 140 patients in the control group, who received conventional care (P = 0.09). There were 94 readmissions in the control group and 53 in the treatment group (risk ratio, 0.56; P = 0.02). The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group (54 vs. 24, P = 0.04), whereas the number of readmissions for other causes was reduced by 28.5 percent (40 vs. 29, P not significant). In the control group, 23 patients (16.4 percent) had more than one readmission, as compared with 9 patients (6.3 percent) in the treatment group (risk ratio, 0.39; P = 0.01). In a subgroup of 126 patients, quality-of-life scores at 90 days improved more from base line for patients in the treatment group (P = 0.001). Because of the reduction in hospital admissions, the overall cost of care was $460 less per patient in the treatment group.A nurse-directed, multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure.
RECURRENT VENOUS THROMBOEMBOLISM IN PULMONARY EMBOLISM PATIENTS WITH RIGHT VENTRICULAR DYSFUNCTION IN THE HOKUSAI-VTE STUDY
Authors: Marjolein Brekelmans, Walter Ageno, Ludo F. Beenen, Benjamin Brenner, Harry Buller, Cathy Chen, Alexander (Ander) Cohen, Michael Grosso, Guy Meyer, Gary Raskob, Annelise Segers, Thomas Vanassche, Peter Verhamme, Philip S. Wells, George Zhang, Jeffrey Weitz
Journal: Journal of the American College of Cardiology (2016)
Differentiated therapy in pre- and postmenopausal adnexal torsion based on malignancy rates: A retrospective multicentre study over five years
Authors: Aykut Ozcan, Sezcan Mumusoglu, Mehmet Gokcu, Sema Süzen Caypinar, Cengiz Sagiroglu, Abdurrahman Hamdi Inan, Fatih Aktoz, Alper Biler, Volkan Turan, Emrah Töz, Isa Aykut Ozdemir, Gurkan Bozdag
Journal: International Journal of Surgery (2016)
The Use of Sodium Bicarbonate in the Treatment of Acute Bronchial Asthma
Authors: John C. Mithoefer, Richard H. Runser, Monroe S. Karetzky
Journal: New England Journal of Medicine (1965)

ACUTE respiratory insufficiency from bronchial asthma usually responds promptly to treatment with epinephrine or other bronchodilators. A significant number of cases, however, do not respond favorably, and many innovations in therapy have been directed toward this group of patients. Among the recommendations that have been made are larger than usual doses of epinephrine,1 , 2 or its administration by the intravenous route,3 intravenously given aminophylline,4 ether by rectum,5 general anesthesia,6 , 7 adrenal steroids,8 , 9 hypnosis,10 artificial respiration,11 sedation12 and newer sympathomimetic agents.13 These methods, however, are not always successful in overcoming bronchospasm when conventional use of epinephrine has failed, and the mortality in bronchial . . .
565 INTERFERON GAMMA INDUCIBLE PROTEIN (IP)-10 LEVELS IDENTIFY INDIVIDUALS WITH RAPID FIBROSIS AT 12 MONTHS POST-TRANSPLANT FOR HCV
Authors: D. Joshi, I. Carey, M. Foxton, M. Al-Freah, M. Bruce, N. Heaton, A. Quaglia, J. O'Grady, V. Aluvihare, K. Agarwal
Journal: Journal of Hepatology (2013)
Excellent long-term experience with primary bone lymphoma: Analysis of prognostic factors
Authors: K. P. Beal, L. F. H. Allen, J. Yahalom
Journal: Journal of Clinical Oncology (2004)

6587 Background: There is limited information on the preferred treatment and long term prognosis of primary bone lymphomas (PBL). We analyzed all PBL cases treated at our center between 1963 and 2003 to determine patient, disease, and treatment factors that could affect outcome measured by overall survival (OS), cause specific survival (CSS), and freedom-from-treatment failure (FFTF). Methods: 101 patients with PBL diagnosed at our institution were identified. 19 patients were excluded as they transferred their treatment or follow-up to another center. 82 patients were analyzed for prognostic factors by performing a univariate analysis and subjecting the significant factors to a Cox regression multivariate analysis. Results: Median age was 48 years (range 11:83); the M:F ratio was 1:1; 80% presented with DLCL; 81% presented with stage I or II disease; 57% were treated with combined modality therapy (CMT), 14% were treated with radiation therapy alone, 30% were treated with chemotherapy alone. The median follow-up was 67 months (range 2:280). The 5-year OS, CSS, and FFTF was 88%, 96% and 81% respectively. The 5 year OS for patients treated with CMT was 95% vs. 78% (p=0.013) for patients treated with single modality therapy, and the 5 year FFTF for patients treated with CMT was 90% vs. 67% (p=.025). The 5 year CSS for patients treated with CMT was 95% vs. 83% (p=.065). On univariate analysis age <40, use of CMT, lack of B symptoms, normal LDH level, and female gender were favorable prognostic factors for OS; KPS>=70%, use of CMT, normal LDH level, and female gender were prognostic for FFTF; and only female gender was prognostic for CSS. IPI was not significant for OS, CSS, or FFTF. On multivariate analysis, age <40, use of CMT, and normal level LDH were favorable prognostic factors for OS; age <40, use of CMT, normal LDH level, and lack of B symptoms were prognostic for CSS; and age <40 and use of CMT were prognostic for FFTF. Conclusion: This largest published experience with PBL demonstrates that primary lymphoma involving the bone has an excellent prognosis. Patients with PBL treated with CMT versus single modality therapy had a superior outcome with a significantly better survival. No significant financial relationships to disclose.
Abstract 1588: Transformation of primary human fallopian tube secretory epithelial cells: A cell of origin for high-grade serous ovarian carcinoma
Authors: Alison M. Karst, Keren Levanon, Ronny Drapkin
Journal: Cancer Research (2011)

Abstract High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently required. Progress in these areas has been impeded by our poor understanding of HGSOC pathogenesis. The vast majority of ovarian cancer research is been based on the hypothesis that HGSOC develops from ovarian surface epithelial cells. However, recent studies suggest that &amp;gt; 50% of high-grade serous carcinomas involving the ovary likely arose from secretory cells of the fallopian tube epithelium. Consequently, current ovarian-based experimental models of HGSOC are inadequate in representing the full spectrum of the disease. The aim of our study was to develop the first experimental model of fallopian tube secretory epithelial cell (FTSEC) transformation and to use this model to answer three basic questions: 1) Can FTSECs be transformed in vitro?, 2) What genetic alterations are capable of transforming FTSECs?, and 3) Do transformed FTSECs give rise to high-grade serous carcinomas? To this end, we isolated primary human FTSECs from fresh samples of normal fallopian tube fimbriae and immortalized them via transduction with hTERT and SV40 TAg. Immortal FTSECs were transformed by either H-RasV12 or c-Myc expression, resulting in accelerated proliferation, enhanced clonogenicity, anchorage-independent growth, and tumor formation in immunodeficient mice. When SV40 TAg was replaced with equivalent non-viral genetic alterations (sh-p53, CDK4R24C, and sh-PP2A-B56γ), FTSECs remained susceptible to c-Myc-induced transformation and tumorigenesis. These results indicate that hTERT expression plus combined dysfunction of the p53, Rb, and PP2A tumor suppressor pathways is sufficient to support c-Myc-mediated transformation. Importantly, all of the transformed FTSECs in our study produced high-grade serous tumors with Müllerian and epithelial characteristics. Moreover, these tumors were grossly, histologically, and immunophenotypically consistent with human HGSOC. The genetic elements employed by our model represent the most common genomic alterations in human HGSOC – namely, TP53 mutation, RB1 dysfunction, and c-MYC amplification – and are therefore appropriate for modeling this disease. In summary, we have presented the first proof-of-principle evidence that FTSECs can be transformed into high-grade serous carcinomas resembling HGSOC. Our FTSEC transformation model provides a novel framework for assessing the transformative effects of specific genetic alterations on primary FTSECs and thus determining what role they may play in the pathogenesis of HGSOC. 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 1588. doi:10.1158/1538-7445.AM2011-1588
Prospective Study of Vitamin D Levels in Sydney Patients with a New Diagnosis of Breast Cancer.
Authors: C. Harris, J. Lynch, D. Thomas
Journal: Cancer Research (2009)

Abstract Background: Vitamin D deficiency has been associated with malignancy in many reported studies. More recently an association has emerged between low levels of vitamin D and poorer outcome in breast cancer. Australian recommendations for vitamin D are defined as deficient if 25-OH vitamin D levels are ≤ 50nmol/L and severely deficient if ≤12.5nmol/L. We hypothesise that lower levels of vitamin D are associated with a more advanced disease at diagnosis.Methods: We conducted a prospective study in patients with a new diagnosis of breast cancer who presented to our area health service from January 1st 2008 to October 1st 2008. Patients were also included if their diagnosis occurred in the preceding 6 months and were referred onto the multidisciplinary breast care team for treatment in this time period. 25-OH vitamin D levels were measured for each patient during staging and details collected about each patients breast cancer characteristics. Patients completed a questionnaire assessing comorbidities, medications, diet and lifestyle effects which were likely to influence vitamin D levels. We used stage, disease requiring chemotherapy, and the need for mastectomy as surrogate endpoints for assessing disease extent.Results: 166 patients were recruited with a median age of 58 (range 21-100). The median vitamin D level was 48 (range of &amp;lt;10 to 170). 53% (n=88) patient were deficient (25-OH vitamin D ≤ 50nmol/L), 2% (n=3) patients were severely deficient (25-OH vitamin D ≤ 12.5nmol/L) and only 14% had sufficient levels (25-OH vitamin D &amp;gt;75nmol/L). The majority of patients reported the recommended sun exposure during weekdays (77%) and on weekends (86%). Most were had fair or medium skin tones (83%) and less than 10% wore sunscreen daily. Only 22% of patients had a potential identifiable cause for vitamin D deficiency. Vitamin D levels did not correlate directly with stage of disease (RR 1.03, 95% CI 0.86-1.23 p=0.85), however other surrogates for more advanced disease including the need for more aggressive treatment either with chemotherapy (RR 1.30, 95% CI 1.05-1.61 p=0.02) or mastectomy (RR 1.67 95% CI 1.03-2.7 p=0.04) were associated with low levels of vitamin D.Conclusions: Vitamin D deficiency is very prevalent in our population of patients diagnosed with breast cancer, despite perceived adequate sun exposure and lack of obvious cause. Lower levels of vitamin D did not directly correlate with more advanced stage of the disease at diagnosis; however patients with low levels of vitamin D were more likely to need chemotherapy or require mastectomy, which may suggest a more aggressive disease. The cause of breast cancer remains multifactorial and vitamin D deficiency is only one part of this complex disease. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6071.
Abstract 4731: Discovering cancer biomarkers using a novel cytokine screening panel.
Authors: Joseph Manimala, Prachi Gupte, Ashok Swaminathan, Jorge P. Tituana, Caitlin Hansen, Anu Mathew, David Stewart, Pankaj Oberoi, Jacob Wohlstadter
Journal: Cancer Research (2013)

Abstract Cytokines and chemokines that are produced in the tumor micro-environment play major roles in tumorigenesis, tumor progression, and apoptosis. They are involved in the modulation of angiogenesis and consequently, in tumor growth and metastases. Cytokine/chemokine expression by tumor cells leads to tumor proliferation and enhances tumor cell survival. Profiling these biomarkers may be useful for cancer diagnosis. For example, biomarkers such as IFNγ, TNFα, IL-1β, MCP-1, and IL-8 are overexpressed in breast carcinoma; IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, and TARC are associated with prostate cancer; and increased expression levels of TNFα, IL-6, and IL-1β are implicated in colon cancer. We have developed and validated multiplexed panels of 30 assays that allow users to simultaneously detect cytokines and chemokines with high precision and accuracy in different human matrices. These panels detect IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα, IL-5, IL-7, GM-CSF, IL-1α, IL-17A, IL-15, IL-16, IL-12/IL-23 p40, TNFβ, and VEGF MIP-1α, MIP-1β, Eotaxin, Eotaxin-3, IP-10, TARC, IL-8 (high abundance), MDC, MCP-1, and MCP-4. The MSD® platform has the ability to quantitate these biomarkers in multiple sample types with superior sensitivity and performance, quantifying many low abundance analytes at levels below 0.5 pg/mL. A challenge with current multiplex assays is a lack of analytical validation and lot-to-lot reproducibility. These new multiplex panels were developed with highly characterized and qualified reagents, and the assays were developed in accordance with industry guidelines. The panels demonstrated suitable spike recovery and dilution linearity performance in different biological matrices. Diluents, other kit components, and an optimized assay protocol are provided to achieve optimum performance. Each assay in the panel is well characterized and shows low non-specific binding. Each has been evaluated for potential assay and analytical interference. Controls are available for each panel. These panels are suitable tools for accurately quantitating cytokines and chemokines in various tumor samples. Data are presented for samples from normal subjects as well as samples from benign prostatic hyperplasia and prostate cancer patients (serum), cirrhosis and liver cancer patients (serum), kidney cancer patients (plasma), and colon cancer patients (serum). Citation Format: Joseph Manimala, Prachi Gupte, Ashok Swaminathan, Jorge P. Tituana, Caitlin Hansen, Anu Mathew, David Stewart, Pankaj Oberoi, Jacob Wohlstadter. Discovering cancer biomarkers using a novel cytokine screening panel. [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 4731. doi:10.1158/1538-7445.AM2013-4731
Menopause Management — Getting Clinical Care Back on Track
Authors: JoAnn E. Manson, Andrew M. Kaunitz
Journal: New England Journal of Medicine (2016)

Use of systemic hormone therapy has decreased dramatically among U.S. women since the Women's Health Initiative results were published. But those results are being misapplied to treatment decisions for women in their 40s and 50s who have distressing vasomotor symptoms.
A "Harness" Distribution Pattern on Pediatric Ga-67 Scintigraphy
Authors: GUY W. LEWIS, ROBERT MANSBERG, ROBERT HOWMAN-GILES
Journal: Clinical Nuclear Medicine (1999)

An 18-month-old girl was evaluated at our institution for a limp and discomfort on movement of her right lower limb. Because joint or bone infection was suspected, Tc-99m MDP scintigraphy was performed. A mild relative decrease in soft-tissue uptake in the right lower limb was noted, in keeping with disuse. Correlative Ga-67 imaging performed 6 days later showed unexpected abnormal avid uptake in a harness type of distribution over the upper anterior and lateral thorax. No respiratory symptoms were evident, and no pulmonary, pleural, or soft-tissue abnormality was detected clinically or radiologically. The patient's clinical syndrome resolved with treatment of her symptoms. In this case, the abnormal tracer distribution was thought to correspond with the anatomic distribution of the serratus anterior muscle and represents an interesting and extreme variation in the pattern of nonpathologic muscular tracer activity that is sometimes noted in children.