tbuckley/cabot-search huggingface dataset:
Surgical decision making for breast cancer: Treatment preferences prior to surgery.
Authors: Katharine Yao, Kristen Wroblewski, Martha Van Haitsma, Sarah Rabbitt, Jordan Williams, Swati Kulkarni
Journal: Journal of Clinical Oncology (2014)

71 Background: Contralateral prophylactic mastectomy (CPM) rates are increasing but it is unclear how many patients consider CPM prior to their surgery. Methods: We developed a 55 item survey validated with 20 breast cancer survivors which was administered to newly diagnosed breast cancer patients (n=136) at two institutions prior to surgery to determine factors associated with CPM treatment preference. Results: The median age was 58 years (range 30-85). Eighty-three (69.2%) were White. Thirty-eight (28.6%) of patients had a 1st degree relative with breast cancer. Fifty-three patients (39.8%) thought about their surgery choice prior to getting breast cancer. Seventy-four (57.8%) of patients considered undergoing a CPM during decision making process, 31 (24.2%) did not want/consider CPM and 23 (18.0%) did not think CPM was an option. Of the 74 women who considered CPM, 12 (16%) chose CPM. Nearly 70% of women who considered CPM felt that CPM reduced the chance that cancer would come back vs 43.3% of women who did not want/consider CPM (p=0.02) and 86% of women who considered CPM stated that lumpectomy and mastectomy patients have equivalent survival compared to 100% of patients who did not want/consider CPM (p=0.03). Women who considered CPM were more likely to rate the diagnostic process as very/extremely emotionally difficult (47.3% vs 22.6%, p=0.03) and to state that being diagnosed with breast cancer “sent them into a daze” than those not wanting/considering a CPM (37.5% vs 13.3%, p=0.02). Likewise, women considering CPM had higher rates of anxiety (49.3% vs 12.9%, p&lt;0.001) and depression (19.7% vs 3.2%, p=0.03); were more likely to be very/extremely worried about getting cancer elsewhere in their body (43.8% vs 6.5%, p&lt;0.001) and very/extremely worried about how a spouse/partner would feel about their changed body than those women who did not want/consider CPM (18.5% vs 0%, p=0.03). Women who did not think CPM was an option were older (p=0.02), less educated (p=0.05), more often single (p=0.05). Conclusions: Over 50% of newly diagnosed breast cancer patients consider CPM prior to their surgery. Women considering a CPM had greater worry about recurrence, higher anxiety levels and less knowledge than patients not wanting/considering CPM.
Abstract 17301: Increased Pulmonary Vascular and Systemic Response to Chronic Hypoxia in Sirtuin 1 Mutant Mice: a Role for Hypoxia-inducible Factor-3α?
Authors: Mohamad Taha, Yupu Deng, Michael W McBurney, Duncan J Stewart
Journal: Circulation (2014)

Introduction: Pulmonary Hypertension is caused by occlusive remodelling of pulmonary arterioles leading to increased pulmonary vascular resistance, right ventricle hypertrophy and eventually failure. Sirtuin-1 (Sirt1) is an NAD+-dependent deacetylase that has been strongly implicated in endothelium homeostasis in systemic vessels, but little is known about its role in hypoxia sensing. Hypothesis: We assessed the hypothesis that absence of Sirt1 catalytic activity is detrimental to the hypoxic response in mice. Methods: Mice lacking Sirt1 catalytic activity (sirt1Y/Y, H355Y) and their wild type (WT) littermates were exposed to chronic hypoxia (10% O2) for 1, 7 or 21 days. Results: Sirt1Y/Y exhibited an exaggerated increase in right ventricle systolic pressure, apparent within the first week of hypoxic exposure, which progressively increased over the 3 week CH exposure period (42±2 sirt1Y/Y vs. 30±1 WT; n=27/group, p&lt; 0.001). Right ventricular hypertrophy, assessed by the RV/LV+S weight ratio, was also increased (Day 21: 0.56±0.01 sirt1Y/Y vs. 0.43±0.01 WT, n=27/group; p&lt; 0.001). Hemtaocrit levels were similar in Sirt1Y/Y and WT mice at baseline; however, there was a delayed increase after three weeks of CH in Sirt1Y/Y mice relative to WT mice (71±2% sirt1Y/Y vs. 63±1% WT, n=17/group; p&lt;0.001). Plasma levels of erythropoietin (EPO), assessed by ELISA at each time point, were markedly increased at Day 7 in Sirt1Y/Y vs. WT mice (492±240 vs. 81±16pg/mL, respectively; n=7-9, p&lt; 0.05) but normalized at later time points (Day 21: 75±9 sirt1Y/Y vs. 96±12pg/mL WT; n=4/group). Surprisingly, expression of both HIF1α and 2α mRNA was decreased in mutant mice lungs during chronic hypoxia at all time points, as was the expression of several HIF1/2α responsive target genes. However, there was a dramatic increase in HIF3α in Sirt1 mutant vs. WT lungs, which has been implicated both in repression of other HIFs as well as in directly mediating hypoxic signaling. Conclusions: Loss of Sirt-1 deacetylation activity led to an exaggerated pulmonary and systemic response to hypoxia, consistent with a role for Sirt1 in hypoxia sensing and/or signaling. As well, our data suggest that HIF3α is a novel downstream target for Sirt1 in the regulation of the response to chronic hypoxia.
Prognostic significance of children with cutaneous melanoma: Implications for treatment
Authors: M. A. Kavanagh, R. Essner, S. L. Chen, L. A. Wanek, R. P. Scheri, D. L. Morton
Journal: Journal of Clinical Oncology (2006)

8021 Background: The incidence of melanoma in pediatric patients, particularly teenagers, is increasing. Treatment strategies employed for adult patients with melanoma have been applied to pediatric populations with minimal data to support similar efficacy. We performed a matched-paired analysis to compare the prognosis of pediatric (≤19 yrs old) and adult melanoma patients. Methods: Single institution, prospectively obtained melanoma database containing &gt;14,000 records was queried for children ages 1–19 years treated for cutaneous melanoma. We identified 197 pediatric patients seen at our institute over the last 35 years. After excluding patients not seen within 4 months of initial diagnosis, 115 pediatric patients were matched to adults (age 20–70 years) chosen from the database by gender, stage, primary site and tumor characteristics (Clark level, Breslow thickness, and ulceration). Overall survival was compared between cohorts by the Kaplan-Meier method. Results: For the pediatric patients, median age at diagnosis was 17.7 years (range 7–19 years). Patients were almost equally distributed between girls (47%) and boys. AJCC stage I and II disease at presentation was most common (73%), with stage III and IV occurring much less frequently (25% and 2%). Most pediatric patients had Clark level IV (37%) lesions; Clark level II (25%), III (25%), V (4%), and I (2%) lesions were less common. Breslow thickness ranged between &lt;1.0mm (38%), 1.1–2.0mm (20%), 2.1–4.0mm (17%), and &gt;4.1mm (12%). The two predominant histologic types were superficial spreading (52%) and nodular (22%) melanoma. 14% of the primary lesions were ulcerated. Rates of disease-free and overall survival were 75%± 4% and 84%± 4% at 5 years and 74%± 4% and 77%± 5% at 10 years, respectively, with a median follow up of 5.1 years (range 1–30 years). Matched pediatric and adult patients showed no difference in survival from time of initial diagnosis and stage of presentation (log rank p=0.24). Conclusions: Stage-specific survival in pediatric and adult melanoma patients is similar. In the absence of specific pediatric trials, standard treatment for children with melanoma should be consistent with that for adults. No significant financial relationships to disclose.
In vitro effect of low dose resveratrol and tri-acetyl resveratrol on Wnt signaling in colon-derived and colon cancer cell lines
Authors: Joseph Hanson, Christopher Hope, Kestutis Planutis, Patrick Farmer, Randall Holcombe
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5534 

BACKGROUND: Resveratrol (RES) is a bioflavonoid found in the skin of dark grapes and red wine which has antioxidant and pro-apoptotic activity, has been shown to inhibit colon cancer cell proliferation at high dosages (> 100uM) in vitro, and has cancer prevention activity in animal models. It has been proposed for use in colon cancer prevention in humans. However, it is unclear if a biologically equivalent concentration could be achieved in humans when considering dosages utilized in vitro and in animal models. We have examined the activity of low dose RES on cell proliferation and on Wnt signaling in vitro and compared this to a chemically modified derivative, tri-acetyl resveratrol (TAR). TAR has increased hydrophobicity which would facilitate cellular uptake of the compound both in vitro, and in vivo by colonic mucosa. METHODS: The effects of low dose (< 40uM) RES and TAR on proliferation and Wnt signaling were examined in a normal-derived colon cell line (NCM460) and a colon cancer cell line lacking intrinsic Wnt pathway activation (RKO) by MTT assay and a luminescence-based LEF/TCF reporter assay respectively. RESULTS: Neither RES nor TAR affected proliferation of NCM460 at concentrations from 2.5uM to 40uM. Proliferation of RKO was inhibited by both RES and TAR at 20uM and 40uM, with TAR exhibiting a slightly greater inhibitory effect at each concentration. The effects of RES and TAR on Wnt throughput were measured following treatment of cells with Wnt3a conditioned medium (CM) to augment basal Wnt signaling. Both NCM460 and RKO had significantly increased Wnt throughput following Wnt3a CM. At 20uM, neither RES nor TAR inhibited Wnt throughput in NCM460. 20uM TAR, but not RES, significantly inhibited the Wnt3a CM induced increase in Wnt throughput in RKO (p=0.025). A non-significant trend toward inhibition was seen with RES in these cells. CONCLUSIONS: We have demonstrated that low concentrations of RES and TAR can inhibit proliferation of colon tumor-derived cells. TAR, but not RES, inhibited Wnt signaling in RKO colon cancer cells but had no effect on the normal-derived colonic mucosal cells, NCM460. This is the first report demonstrating activity of a chemically modified analog of RES on Wnt signaling. The increased efficacy of TAR may be related to improved cellular uptake. Further research on chemically modified analogs of RES on Wnt signaling and on colon cancer is indicated.
THU0460-HPR Psychometric testing of the body awareness questionnaire in an swedish sample of patients diagnosed with rheumatoid arthritis
Authors: H. Lööf, F. Saboonchi, E. Welin Henriksson, S. Lindblad, U.-B. Johansson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The concept of body awareness has come into sight as a subject of scientific research and it has been suggested to be useful in the management of chronic disease [1]. The Body Awareness Questionnaire (BAQ) is an 18-item scale to measure self-reported attentiveness to normal body processes [2]. It has been identified as an instrument with strong psychometric properties [1]. However, there is no validated Swedish version available. <h3>Objectives</h3> To develop and to test the psychometric properties of the Swedish version of the BAQ for measuring bodily focused of attention in a population of patients diagnosed with rheumatoid arthritis (RA). <h3>Methods</h3> The study employed a cross-sectional design and a psychometric validation study was developed. The study population consisted of a convenience sample of 120 patients with RA. Psychometric testing included concurrent think aloud method (n=10) to investigate usability and to understand how the patients' perceive and interpret the questions in the BAQ and Cronbachs alpha coefficients was used to test the internal consistency. Confirmatory factor analysis of the data was conducted using the sem package in R to test the factor structure to investigate the construct validity. <h3>Results</h3> The majority of the participants' were able to comprehend (= understanding) all the items in BAQ 1-18, retrieve (=retrieval) all the necessary information from long-term memory, make a judgment (=judgment) about the information needed to answer the items in BAQ, and respond (responding) to the statements in the BAQ item 1-18. Cronbach's alpha of the overall BAQ 18- item was satisfactory 0.90 in the RA sample. The result of the CFA indicate that the one-factor model have most adequate fit with CFI=0.747 compared to CFI=0.560 for four-factor model. <h3>Conclusions</h3> The one-factor model displayed the most acceptable fit of the Swedish version of the BAQ. Although further testing of the BAQ scale with different sample is necessary. <h3>References</h3> Mehling. W.E., Gopisetty. V, Daubenmier, J., Price. C.J., Hecht. F.M. &amp; Stewart. A. Body Awareness: Construct and Self-Report Measures. PLoS One. 2009; 4: e5614. Shields S. A., Mallroy M. E., &amp; Simon. A. The body awareness questionnaire: reliability and validity. Journal of Personality Assessment. 1989; 53: 802-815. <h3>Disclosure of Interest</h3> None Declared
Mechanisms of bone metastasis (BM) growth in patients with metastatic breast cancer (MBC): An exploratory study
Authors: W. S. Ooi, S. Popovic, M. Kalina, K. Harriette, G. Singh, M. C. Gainford, M. Clemons
Journal: Journal of Clinical Oncology (2007)

1102 Background: The benefits of bisphosphonates (BPs) in reducing or delaying skeletal related events (SREs) in patients with BM have been attributed to their potent osteoclast (OC) inhibiting effect. However, despite the use of modern systemic anti-cancer therapy including potent BPs, many patients with BM continue to suffer from the consequences of their bone disease. An improved understanding of the basic mechanisms of bone destruction would allow further appropriate targeted treatment strategies to be developed. Methods: Archival paraffin embedded BM specimens from patients with MBC were examined for expression of OCs, receptor activator of nuclear factor kappa B (RANK), RANK Ligand (RANKL) and Osteoprotegerin (OPG). Histological specimens were also available for primary breast cancer, lymph node (LN) metastasis, normal breast and bone tissues for comparison. Results: BM specimens were available for 20 BP naïve pts and 2 pts treated with BP. OCs were significantly increased in the BM of the BP naive group compared to controls. There were no OCs seen in the BP treated group. RANK was expressed on tumor cells (TCs) in the both bone and nodal metastases but not on the primary cancer cells. It is also expressed on the OCs which were present in both BM and normal bone. While RANKL was absent in TCs, it was strongly expressed in all stromal cells (SCs) in all specimens and in osteoblasts. The OPG, while present in TCs of the BM and LN metastases, is not detected in the primary cancer. Conclusion: The mechanism of bone destruction in MBC are not fully understood and are clearly multifactorial. OCs may not be the singular obligatory factor for osteolysis in BM. Further investigation of various inhibitors of the RANK/RANKL/OPG pathways, may allow novel treatment strategies to be developed. No significant financial relationships to disclose.
Abstract 18429: The Impact of Preoperative Malperfusion on Outcome of Acute Type a Aortic Dissection - Results From Geraada
Authors: Martin Czerny, Florian Schönhoff, Christian Etz, Lars Englberger, Nawid Khaladj, Andreas Zierer, Isabell Hoffmann, Maria Blettner, Thierry Carrel
Journal: Circulation (2014)

Introduction: Malperfusion may affect outcome in patients with acute type A aortic dissection (AAD). Reliable quantitative data are lacking

Hypothesis: Aim of the current study was to analyze the impact of various forms of malperfusion on outcome in patients undergoing surgery for AAD.

Methods: We retrospectively analyzed 2137 consecutive patients enrolled in the German Registry for Acute Aortic Dissection type A (GERAADA) who were operated between 2006-2010.

Results: Overall 30-day mortality was 16.9%. Mortality differed significantly according to the number of organ systems affected by malperfusion (n=0, 12.6%; n=1, 21.3%; n=2, 30.9%; n=3, 41.7%, p<0.0001). Preoperative peripheral malperfusion ( OR 1.6 , CI 1.1-2.2, p=0.008), comatous state ( OR 1.6 , CI 1.1-2.3, p=0.02), cerebral malperfusion ( OR 1.6, CI 1.1-2.2, p=0.02), visceral malperfusion ( OR 1.7 , CI 1.1-2.7, p=0.03), extension of dissection into supraaortic branches ( OR 1.7 , CI 1.3-2.3, p=0.002), coronary malperfusion ( OR 1.8 , CI 1.2-2.7, p=0.004) and renal malperfusion ( OR 2.5 , CI 1.7-3.7, p<0.0001), were independent predictors of any persisiting postoperative malperfusion syndrome in increasing significance.

Age ( OR 1.02 , CI 1.01-1.03, p<0.0001), peripheral malperfusion ( OR 1.4 , CI 1.0-2.0, p=0.04), involvment of the supraaortic branches ( OR 1.5 , CI 1.1-1.9, p=0.004), coronary malperfusion ( OR 1.6 , CI 1.1-2.3, p=0.01), spinal malperfusion ( OR 2.2 , CI 1.1-4.3, p=0.03), primary entry in the descending aorta ( OR 2.8 , CI 1.4-5.6, p=0.004) and comatous state ( OR 3.4 , CI 2.5-4.7, p<0.0001) were independent predictors of decreased survival.

Conclusions: Malperfusion remains a strong condition for adverse outcome in patients undergoing surgery for AAD. Our data suggest that the impact of the number of organ systems involved as well as the type of malperfusion may substantially influence outcome. Additional classification such as “complicated” and uncomplicated” AAD might increase the individual risk assessment and help to choose the most appropriate malperfusion-oriented surgical strategy.
Experience with breast cancer in a single oncology clinic in Nairobi
Authors: N. A. Othieno-Abinya, H. O. Abwao, P. Bird, R. Baraza, B. Byakika, Y. Kodwavwalla
Journal: Journal of Clinical Oncology (2006)

10714 Background: Combinations of anthracyclines and cyclophosphamide ± 5-FU are widely used in treatment of breast cancer (BC) in the adjuvant setting. Addition of taxanes is beneficial. For Her2-positive tumours addition of herceptin may improve relapse-free survival in the adjuvant setting, and prolongs survival in metastatic setting. We routinely use doxorubicin and cyclophosphamide (AC) x 6 courses for standard risk disease and give the same x 4 followed by docetaxel ± herceptin x 4 for those with ≥ 10 positive axillary nodes. We also use AC as first line for endocrine nonresponsive metastatic BC. Methods: A total of 173 BC patients seen in our clinic between January 1997 and May 2005, 83 were given chemotherapy both in the adjuvant and metastatic settings. Results: Of 83 patients, 81 were female and 2 males, age range 24–71, median 45 years. Seventy-eight cases were ductal carcinoma, not otherwise stated, 1 colloid, 1 anaplastic, 1 adenosarcomatoid, 2 medullary. Fifty-six were post resection and 27 metastatic. Thirty eight sites of metastasis or spread were evaluable. These were skeletal 10 (26.3%), liver 7 (18.4%), chest wall 6 (15.9%), lungs and pleura 9 (23.7%), brain 4 (10.5%) and supraclavicular nodes 2 (5.3%). Her2 expression by immunohistochemistry in 20 cases was - 3+ in 7 (35%), 2+ in 3 (15%) and ≤ 1+ in 10 (50%). Out of 40 cases, 15 (37.5%) were endocrine responsive, 17 (42.5%) nonresponsive and 8 (20%) indeterminate. Twenty seven patients treated before January 2004 were recorded dead after survival ranging between 8 and 96 months, median 36 months. Only 3 patients with resected BC were recorded dead as opposed to 24 with MBC at diagnosis. Two of the deaths in the adjuvant setting were in patients with ≥ 10 nodes positive and both had the brain as the only site of metastasis. There was no significant correlation between nodal status and follow-up duration (P = 0.43), hormone receptor status and survival (P = 0.20), and Her2-expression and survival (P = 0.23). Conclusions: This material shows a low frequency of ER positivity and higher mortality particularly from brain metastasis than most Western series. It does however show a similarity to recent reports of breast cancer in African-American women. No significant financial relationships to disclose.
Temporal characterization of murine genomic response to poly I:C stimulation reveals tri-phasic inflammatory response signatures
Authors: Sriram Sridhar, Paul Harris, John Allard, Ruoqi Peng, Palani Ravindran, Hans Bitter, Michael E. Burczynski, Jay S. Fine, Christopher S. Stevenson
Journal: European Respiratory Journal (2011)

Introduction:  Poly I:C mimics a viral infection through the activation TLR3 and RNA helicases. Our aim was to characterize molecular changes occurring in the lung after polyI:C exposure in mice.   Methods:  BALB/c mice were administered saline or poly I:C (30 μg/animal). At 7 timepoints after dosing (2-168h), poly I:C- and saline-treated mice were sacrificed, bronchoalveolar lavage was performed and lungs were snap-frozen. RNA from lung homogenates was isolated using the NuGen labeling method and assessed on Affymetrix standard murine whole genome arrays (MOE430 2.0) (n=6 per group). Differentially expressed genes were determined using an ANOVA, with pairwise comparisons between poly I:C and saline treatment at each timepoint. Functional ontologies were determined using GO annotations. Gene set enrichment analysis (GSEA) was determined for cytokine and immune cell signatures compiled from the literature.   Results:  The peak response occurred 6-48h post-treatment. Hierarchical clustering across the study revealed 3 distinct temporal clusters (early, mid, and late phase). Inflammatory processes were enriched in the early phase (2-6h), TLR/IL-1 signaling genes in the mid phase (6-48h), and cell cycle pathways in the late phase (>72h). GSEA revealed activated NK and dendritic cell signatures up to 96h post-challenge, while several immune and myeloid related gene modules were also up-regulated between 6-96h post-challenge.   Conclusions:  Inflammatory signatures including TLR and IL1-related genes were highly up-regulated in response to poly I:C challenge, indicating a strong inflammatory response potentially driven by NK and dendritic cells in the lungs of mice.
Common Genetic Influences on fasting insulin and waist circumference: The Japanese American Family Study
Authors: Karen L. Edwards, Stephanie A. Monks, Renee LeBoeuf, Donna Leonetti, Philippa J. Talmud, Steve Humphries, Melissa A. Austin, Wilfred Y. Fujimoto
Journal: Circulation (2001)

P13 The Insulin Resistance Syndrome (IRS) increases risk for both cardiovascular disease (CVD) and diabetes. While the underlying defect may be insulin resistance itself, others have suggested that central adiposity is the primary defect. Further, these risk factors are highly interrelated, but it is not known if genetic and/or environmental factors influence this relationship. The purpose of this analysis was to evaluate evidence for shared genetic and environmental effects on the covariation of fasting plasma insulin level (FI), a marker for insulin resistance, and waist circumference (WC) in 315 Japanese Americans with complete data (in 38 families) participating in the Japanese American Family Study, in Seattle. Subjects ranged in age from 18-94 (mean=54.8, SD=16), and 52% were female. Insulin was measured from a fasting blood sample, and waist circumference was self-measured using a tape measure and specific instructions provided to each participant. Quantitative genetic analysis was used to evaluate genetic (ρ G ) and environmental (ρ E ) correlations between FI and WC, adjusting for age, gender, and body mass index. A significant (p&lt;0.05) proportion of the variance in each trait was attributable to additive genetic effects: heritability =0.29 and 0.23 for FI and WC, respectively. The strong and significant (p&lt;0.01) ρ G =0.83 reflects shared genetic influences between FI and WC, indicating that the majority of genes that influence FI also influence WC. Further, ρ G was not significantly different from 1.0, suggesting the possibility of nearly complete genetic pleiotropy between these risk factors (i.e. that FI and WC share all their genes in common). Estimated ρ E =-0.08, but was not significantly different from zero. These results are the first to suggest complete pleiotropy between FI and WC. Incorporating these results into future gene mapping studies should increase power to detect susceptibility genes for not only CVD and diabetes, but also central adiposity.