tbuckley/cabot-search huggingface dataset:
Abstract 5225: Single-cell gene-expression programs and basal-like breast cancer.
Authors: Chun-Chao Wang, Leen Jamal, Sameer S. Bajikar, Kristen A. Atkins, Kevin A. Janes
Journal: Cancer Research (2013)

Abstract Basal-like carcinoma is a subtype of breast cancer that is characterized by poor prognosis and high intratumor heterogeneity. In basal-like breast epithelia, we have identified two anticorrelated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first program contains multiple TGFβ-related genes including TGFBR3, and its heterogeneous induction is critical to suppress ductal branching. The second program contains JUND together with the basal-like marker, KRT5. Homogenizing JUND expression in single cells leads to 3D acini with bridged lumina that are similar to cribiform ductal carcinoma in situ. TGFBR3 and JUND together comprise a circuit that is interconnected via four negative-feedback loops. Computational modeling of the circuit predicts damped, antiphase oscillations upon stimulation with endogenous impulses of TGFβ-like ligand, and we directly observe these spontaneous responses in 3D culture by live-cell imaging. The TGFBR3-JUND circuit is remarkably conserved in early basal-like tumors that heterogeneously express KRT5, suggesting that asynchronous circuit dynamics are active in this patient subset. We further show that the circuit is strongly dependent on ECM engagement, as detachment leads to a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine signaling from tenascin C. Breast tumor heterogeneity need not stem from partial basal-like differentiation and could instead reflect dynamic toggling of individual cells between expression states. Citation Format: Chun-Chao Wang, Leen Jamal, Sameer S. Bajikar, Kristen A. Atkins, Kevin A. Janes. Single-cell gene-expression programs and basal-like breast cancer. [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 5225. doi:10.1158/1538-7445.AM2013-5225
Phase II Study of Intravenous Bolus Recombinant Interleukin-2 in Advanced Malignant Melanoma: Southwest Oncology Group Study
Authors: Robert P. Whitehead, Kenneth J. Kopecky, Michael K. Samson, John J. Constanzi, Ronald B. Natale, Lynn G. Feun, Evan M. Hersh, John J. Rinehart
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Phase II Study of Intravenous Bolus Recombinant Interleukin-2 in Advanced Malignant Melanoma: Southwest Oncology Group Study Get access Robert P. Whitehead, Robert P. Whitehead Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth J. Kopecky, Kenneth J. Kopecky Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael K. Samson, Michael K. Samson Search for other works by this author on: Oxford Academic PubMed Google Scholar John J. Constanzi, John J. Constanzi Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald B. Natale, Ronald B. Natale Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn G. Feun, Lynn G. Feun Search for other works by this author on: Oxford Academic PubMed Google Scholar Evan M. Hersh, Evan M. Hersh Search for other works by this author on: Oxford Academic PubMed Google Scholar John J. Rinehart John J. Rinehart Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Pages 1250–1252, https://doi.org/10.1093/jnci/83.17.1250 Published: 04 September 1991 Article history Received: 14 January 1991 Revision received: 28 May 1991 Accepted: 03 June 1991 Published: 04 September 1991
Effect of Chronic Anticonvulsant Therapy on Serum 25-Hydroxycalciferol Levels in Adults
Authors: Theodore J. Hahn, Barry A. Hendin, Cheryl R. Scharp, John G. Haddad
Journal: New England Journal of Medicine (1972)

Abstract A survey of 48 adult epileptic outpatients receiving chronic combined phenobarbital and diphenylhydantoin therapy demonstrated significant hypocalcemia in 19 per cent, and significantly decreased serum 25-hydroxycalciferol in 33 per cent of patients, as compared to 38 untreated controls. Similar but less marked changes were seen in a group of 13 patients given chronic therapy with either phenobarbital or diphenylhydantoin alone. Elevation of serum alkaline phosphatase in the patients receiving chronic therapy with either or both of these agents was attributable to increases in both the hepatic and bone isoenzyme fractions. Serum calcium correlated positively with serum 25-hydroxycalciferol in both the patient and the control groups. Serum 25-hydroxycalciferol also correlated positively with vitamin D intake in the patient and control groups, but at any given intake of vitamin D, mean serum levels were lower in the patient group. Lowest serum calcium and 25-hydroxycalciferol levels were seen in th...
AB0721 Risk of suicide in patients with systemic lupus erythematosus
Authors: C. Belmira de Souza, A. Ferrari, M.T. Pereira, L. Abreu, K. Pereira, L.T. Costallat, S. Appenzeller
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A suicide attempt is an of self inflicted damage accompanied by explicit or implicit to cause death. Although only 1 in 8-10 people who attempt suicide are successful, it remains a leading cause of death. Chronic diseases is an important risk factor for suicide. Systemic lupus erytemathosus (SLE) is a risk factor five times greater than healthy people. Many factors can contribute to this occurrence, such as mood disorders (anxiety and depression), disease activity, corticosteroids, wich can induce mental disorder. <h3>Objectives</h3> To asses the risk of suicide in patients with SLE and to determine associated factors such as anxiety and depression. <h3>Methods</h3> We performed a cross-sectional study including 55 consecutive SLE patients, treated at the Rheumatology Unit of The State UNiversity of Campinas. Psychological features (anxiety, depression and suicidal thoughts) were assessed through a clinical interview using the Mini International Neuropsychiatric Interview (Mini), validated in Portuguese. <h3>Results</h3> The average age of the patients was 33 years (SD=12.8, variance: 14-63). Thirteen/55 (23,63%) patients wished to be dead, and 8/13 (51,63%) of these patients had moderate/severe anxiety and depression. Four/55 (7.27%) already thought of a way to commit suicide and 1/55 (1,82%) and 4/55 (7,27%) reported having attempted suicide at some point in life. All these patients had severe anxiety and/or depression. <h3>Conclusions</h3> The increased levels of anxiety and depression is commonly is SLE patients. Anxiety and depression affect the overall functioning of the individual and the degree of disability, since it can produce a negative impact on the physical, social, occupational, educational and leisure due to apathy, decreased affection, feelings of abandonment and negative beliefs about the future. So these are factors that must be observed at each visit in order to advise and intervene in possible damage. <h3>Disclosure of Interest</h3> C. Belmira de Souza Grant/Research support from: FAPESP 2010/18517-1, A. Ferrari Grant/Research support from: FAPESP 2011/13905-6, M. Pereira: None Declared, L. Abreu: None Declared, K. Pereira: None Declared, L. Costallat: None Declared, S. Appenzeller Grant/Research support from: FAPESP 2008/02917-0; Conselho Nacional Pesquisa Desenvolvimento-Brasil CNPq (300447/2009-4)
Abstract 287: Chamber Specific Function of p38 MAP Kinases in Right Ventricle Development, Hypertrophy, and Dysfunction
Authors: Tomohiro Yokota, Vincent Ren, Yibin Wang
Journal: Circulation Research (2014)

Background: Postnatal heart maturation is a well orchestrated process involving chamber specific changes in myocyte proliferation and growth. While the left ventricle undergoes significant growth, the right ventricle regresses relative to the left in terms of both myocyte number and size. While much attention has been focused on the left ventricular myocyte proliferation and hypertrophy, right ventricle specific changes are poorly studied. p38 MAP kinase is a well established signaling pathway for stress response and also plays an important role in cell differentiation, viability and proliferation. Its role in chamber specific postnatal heart maturation, however, has not been demonstrated Results and Methods: We observed RV specific induction of myocyte apoptosis and suppression of myocyte proliferation in neonatal hearts, coinciding with a transient induction of p38 activity significantly higher in the RV relative to the LV at P3 and P7 wild-type mouse hearts. In cardiomyocyte specific p38 MAP kinase alpha&amp;beta double KO (p38ab cdKO) mice, echocardiographic and histological analyses revealed RV specific chamber enlargement and dysfunction associated with significant postnatal lethality. Apoptotic activity in the RV was suppressed at P1 and myocyte proliferation and hypertrophy were significantly elevated at P3 and P7 in the p38ab cdKO hearts compared to the wild-type. In contrast, no differences were observed in the LV between the p38ab cdKO and wild-type. Consequently, the surviving p38ab cdKO mice showed significant and RV specific enlargement and dysfunction, leading to eventual RV failure and pulmonary hypertension. Conclusion: p38 a&amp;b MAP kinases are essential to RV specific maturation in postnatal hearts. p38ab cdKO mice represent a unique RV-specific hypertrophy and heart failure model for further studies.
Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial.
Authors: B. I. Rini, B. Escudier, P. Tomczak, A. Kaprin, T. E. Hutson, C. Szczylik, J. C. Tarazi, B. Rosbrook, S. Kim, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

4503 Background: Axitinib is an oral, potent, and selective inhibitor of VEGF receptors 1, 2, and 3. This randomized, open-label, phase III trial compared the efficacy and safety of axitinib versus (vs) sorafenib as second-line therapy for mRCC. Methods: Eligible patients had clear-cell mRCC; measurable, RECIST-defined progressive disease after 1 prior first-line systemic therapy with a sunitinib-, bevacizumab-, temsirolimus-, or cytokine-based regimen; and Eastern Cooperative Oncology Group performance status (PS) of 0 or 1. Patients were stratified by PS and prior therapy, then randomized 1:1 to axitinib, administered at a starting dose of 5 mg BID, titrated to 7 mg BID and then to 10 mg BID as tolerated, or sorafenib 400 mg BID. The primary endpoint was progression-free survival (PFS) per blinded, independent radiographic review. The study had 90% power to detect a PFS of 7 months vs 5 months, corresponding to a hazard ratio (HR) of ≤0.714 (overall 1-sided α=0.025). Results: Seven-hundred twenty-three patients were randomized to either axitinib (n=361) or sorafenib (n=362). Baseline patient characteristics included median age of 61; 72% male; 76% Caucasian; and 55% PS 0. Prior therapy included 54% sunitinib-, 35% cytokine-, 8% bevacizumab-, and 3% temsirolimus-based regimens. Median PFS was 6.7 months (95% confidence interval, 6.3-8.6) for axitinib vs 4.7 months (4.6-5.6) for sorafenib, with a HR of 0.665 (P<0.0001). PFS favored axitinib in both the prior cytokine subgroup (12.1 vs 6.5 months; P<0.0001) and the prior sunitinib subgroup (4.8 vs 3.4 months; P=0.0107). Objective response rates were 19.4% for axitinib vs 9.4% for sorafenib (P=0.0001). Common AEs more frequent with axitinib vs sorafenib were hypertension (40% vs 29%, all grades), fatigue (39% vs 32%), dysphonia (31% vs 14%), and hypothyroidism (19% vs 8%). AEs more frequent with sorafenib were hand-foot syndrome (27% vs 51%), rash (13% vs 32%), alopecia (4% vs 32%), and anemia (4% vs 12%). Conclusions: Axitinib demonstrated a significantly longer PFS and higher objective response rate vs sorafenib with an acceptable safety profile as second-line therapy for mRCC.
Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway
Authors: M. L. Maitland, K. Moshier, J. Imperial, K. E. Kasza, T. Karrison, W. Elliott, S. D. Undevia, W. Stadler, A. A. Desai, M. J. Ratain
Journal: Journal of Clinical Oncology (2006)

2035 Background: Hypertension is a commonly reported toxicity of agents that inhibit the VEGF signaling pathway (VSP). This new class of cancer therapeutics has broad activity, but optimal dosing methods and integration into established treatment regimens could be enhanced by identification of reliable biomarkers. S, a new treatment for advanced renal cell carcinoma, is an orally available inhibitor of multiple VSP kinases including Raf-1 and VEGFR2. To characterize the chronicity and interindividual variability of BP responses to VSP inhibition we collected serial, standardized measures of BP and concurrent steady-state plasma concentrations ([plasma]) of S, from 30 patients (pts). Methods: Pts with advanced solid tumors, ECOG performance status &lt; 2, and screening BP ≤ 140/90 mmHg on no more than one antihypertensive agent took 400mg S twice daily. Prior to therapy and at 3 time points after steady state [plasma] of drug was achieved, pts underwent 24-hour ambulatory BP monitoring with the SunTech Oscar PowerPack 2 (SunTech Medical, Morrisville, North Carolina). Readings were collected every 15 minutes during daytime hours and every 45 minutes overnight. Results: Unweigthed mean and standard deviations (sd) of systolic (SBP) and diastolic (DBP) 24-hr BP measurements were calculated for each pt. for the sessions pre-therapy and when steady state [plasma] S was reached (between days 6–10 after starting treatment). The differences in mean BPs between the two sessions were compared with (and p values reported for) paired t-tests. Regression analysis of [plasma] of S with either DBP or SBP, or change in DBP or SBP, with main effect and interaction terms for albumin, age, and sex revealed no significant correlation between S [plasma] and BP response. Conclusions: BP elevation is a biomarker for VSP inhibition. The known variability (coefficient of variation = 70%) in total S steady state plasma concentrations did not account for the observed variability in BP response. [Table: see text] [Table: see text]
PTU-130 Regulatory T Cells In Acute Liver Failure Are Functionally Intact And May Contribute To Retention Of Neutrophils In Areas Of Hepatic Necrosis
Authors: R Chudasama, Y-Y Chen, H Jeffery, C Thomas, N Murphy, T Whitehouse, DH Adams, YH Oo
Journal: Gut (2014)

<h3>Introduction</h3> Acute liver failure (ALF) is a sterile inflammation with a high mortality. The immunological response to acute liver injury is initiated by the infiltration of innate neutrophils and is followed by an adaptive T cells response. T cells in drug induced skin lesions have been shown to express neutrophil chemoattractant and there is also evidence that regulatory T cells (Tregs) in peripheral blood secrete IL-8. However, little is known on the ability of liver infiltrating T cell subsets to retain neutrophils in ALF or the function of Tregs. Our aim is to investigate the phenotypic features and cytokine profiles of circulating and liver infiltrating T cell subsets from ALF patients with a view of assessing their functional ability to retain neutrophils. <h3>Methods</h3> Distribution and localisation of Liver infiltrating lymphocytes and neutrophils were assessed by immunohistochemistry. Peripheral blood and liver infiltrating lymphocytes were isolated from ALF patients. Intracellular-cytokines expression profiles of the lymphocytes subsets were assessed by flow cytometry. Functional status of T cells including Tregs was assessed by pSTAT5 signalling. <h3>Results</h3> Immunohistochemistry revealed high numbers of neutrophils in ALF compared to chronic diseased livers (109 ± 12.2 vs. 7.1 ± 2.67; p = 0.01) and normal liver (109 ± 12.2 vs. 0.8 ± 0.33; p = 0.0002). Dual immunohistochemistry showed co-localisation of lymphocytes and neutrophils in areas of hepatic necrosis. Neutrophil chemoattractant IL-8 expression in peripheral blood was higher in lymphocyte subsets of ALF patients compared to normal donor, CD3 (2.3 ± 0.54% vs. 0.93 ± 0.4%; p = 0.23), CD4 (2.8 ± 2.2% vs. 1.1 ± 0.7%; p = 0.41), CD8 (2.2 ± 1% vs. 0.61 ± 0.09%; p = 0.43) and Treg (0.8 ± 0.4% vs. 0.2 ± 0.02%; p = 0.48). There was an up-regulation of IL-8 production in Tregs after 7 days of <i>ex vivo</i> expansion compared to day zero (1.63 ± 1% vs. 0.77 ± 0.42%; p = 0.44). IFN-γ expression in ALF peripheral blood compared with normal blood was (23.1 ± 6.2% vs. 11.1 ± 8.4%; p = 0.38) for CD3 (11.72 ± 2.3% vs. 7.8 ± 6.26; p = 0.5) for CD4 and (14.21 ± 3.04 vs. 9.95 ± 8.44; p = 0.58) for CD8 after day seven of <i>ex vivo</i> expression. Importantly, Tregs from both blood and explanted liver of ALF were functional indicated by STAT5 phosphorylation in response to IL-2. <h3>Conclusion</h3> We demonstrated for the first time that lymphocyte subsets including Tregs in ALF produce IL-8, which may contribute to the retention of neutrophils in areas of hepatic necrosis in ALF. We also showed that Tregs and other T cells are functionally responsive to IL-2 in both blood and explanted liver tissue of ALF patients. <h3>Disclosure of Interest</h3> None Declared.
Abstract P3-08-09: Clinical and Pathological Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1
Authors: Y-S Yap, J Wong, M Chan, W-S Yong, K-W Ong, S-K Lo, J Ngeow, B Tan, P Madhukumar, M-H Tan, P Ang, B-T Teh, P-H Tan, AS-G Lee
Journal: Cancer Research (2012)

Abstract Background: Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disorder affecting 1 in 3,000 individuals worldwide. Risk of cancer, including breast cancer, is increased, as NF1 is a tumour suppressor gene. There is limited data on the characteristics of breast cancer in individuals with NF1. Objectives: To study the clinical and pathological characteristics of breast cancer in women with NF1. Methodology: Patients with both NF1 and breast cancer were identified retrospectively from hospital records as well as prospectively when seen at National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH). All women had histologically proven breast cancer and fulfilled at least 2 of the 7 criteria developed by the NIH Consensus Conference for clinical diagnosis of NF1. Germline NF1 mutation sequencing is being performed on patients with blood specimens available. Details on patient demographics, tumour grade, stage, receptor status and clinical outcome were evaluated. The pathological characteristics of NF1-associated breast cancer were then compared to sporadic breast cancers in our 2001–2004 cohort, with a focus on grade and HER2 positivity rate. Results: We identified 13 women with NF1 and breast cancer seen at our institutions from 2001 to present date. Average age of breast cancer diagnosis for women testing positive was 48 years (range 30–64). All 13 patients had invasive ductal carcinoma; of which 5 were stage 3 or 4 at diagnosis. To date, 4 out of 12 patients with stage 1–3 breast cancer have relapsed. Grade, estrogen, progesterone and HER2 receptor status were fully available for 12 patients. Ten out of 12 tumours (83%) were grade 3, compared to 45% (705/1578) among our sporadic breast cancers (p = 0.007). Eight out of 12(67%) NF1-associated breast cancers were HER2 positive (IHC 3+ or FISH positive), compared to 27% (367/1367) in sporadic cancers (p = 0.002). Two other NF1-associated tumours were triple negative, and two were hormone receptor positive and HER2 negative. Six out of 12 (50%) NF1-associated cancers were estrogen receptor (ER) positive, compared to 67% (1124/1689) in sporadic cancers (p = 0.2). Conclusion: Our findings suggest that NF1-associated breast cancer tends to be more aggressive, with a higher frequency of grade 3 and HER2 positive tumours compared to sporadic breast cancer. Further genomic profiling of these tumours (in progress) may elucidate the role of NF1 in breast cancer. This may also have implications for sporadic tumours with somatic NF1 mutations in individuals without NF1. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-09.
Effects of Leukocyte Interferon on Clinical Symptoms and Hormone Levels in Patients with Mid-Gut Carcinoid Tumors and Carcinoid Syndrome
Authors: K. Öberg, K. Funa, G. Alm
Journal: New England Journal of Medicine (1983)

We treated nine patients who had carcinoid tumors of the small intestine, six of whom had the carcinoid syndrome, with daily intramuscular doses of leukocyte inferieron — 3X106 U per day for one month and 6X106 U per day for another two months. Seven patients had previously been treated with streptozocin and fluorouracil, without benefit. Treatment with inferieron ameliorated the manifestations of the carcinoid syndrome and led to prompt and continuing decreases in urinary levels of 5-hydroxyindoleacetic acid and serum levels of human chorionic gonadotropin subunits and pancreatic polypeptide in all six patients with liver metastases, but it had no clear effect in two of three patients with only lymph-node involvement. After the treatment period, five of the six responders had relapses in clinical manifestations and increases in hormone levels. We conclude that interferon is of benefit in treating metastatic small intestinal carcinoid tumors in patients with the carcinoid syndrome. (N Engl J Med 1983; 309:129–33.)
How Much Savings Can We Wring from Medicare?
Authors: Michael Chernew, Dana Goldman, Sarah Axeen
Journal: New England Journal of Medicine (2011)

As the newly formed congressional "super committee" seeks an additional $1.5 trillion in U.S. debt savings over the next 10 years, a logical target of reform is the Medicare program, which accounts for about 15% of federal spending and more of its projected growth.
Chondrocalcinosis of the Knee with Gout and Rheumatoid Arthritis
Authors: Armin E. Good, Robert Rapp
Journal: New England Journal of Medicine (1967)

X-RAY demonstration of multiple articular chondrocalcinosis has been advanced as a useful preliminary diagnostic sign for pseudogout, a disease marked by deposition of calcium pyrophosphate dihydrate (CPPD) crystals.1 When present, chondrocalcinosis is usually most evident in the knee joint, where in turn the menisci usually are most obviously involved.A recent uncontrolled study by Dodds and Steinbach2 reported meniscal calcification in 10 of 31 patients with gout, 6 of whom had involvement of all 4 menisci. Although these authors noted that the calcium deposits were not as heavy as those in reported cases of pseudogout, their findings have cast some . . .
Clinical Application of Blood Transketolase Determinations
Authors: Pierre M. Dreyfus
Journal: New England Journal of Medicine (1962)

A NUMBER of biochemical tests have been designed and employed to aid in the overall assessment of the nutritional state of patients thought to be suffering from a vitamin deprivation. Many of these tests are cumbersome and poorly reproducible, and some lack specificity. In 1953 Horecker and Smyrniotis1 and Racker et al.2 independently discovered that transketolase, one of the enzymes of the hexose-monophosphate shunt, required thiamine pyrophosphate as cofactor. This enzyme, which has been found to exist in a number of mammalian tissues, acts as catalyst in the following steps: Both Brin and his associates3 and Bruns4 have demonstrated the . . .
P121 VIRAL LOAD DECREASE HIGHER THAN 3 LOG AT WEEK 12 OF PEG-INTERFERON ALFA-2b/RIBAVIRIN HCV TREATMENT CORRELATES WITH HCV-SPECIFIC CYTOTOXIC T CELL RESPONSE RESTORATION
Authors: E. Moreno-Cubero, J. Miquel, S. García-Garzón, A. Lázaro, A. Gonzalez-Praetorious, C. Perna, E. Sanz-de-Villalobos, J.R. Larrubia
Journal: Journal of Hepatology (2014)