tbuckley/cabot-search huggingface dataset:
Localization of Radiolabeled Monoclonal Antibody in a Human Soft Tissue Sarcoma Xenograft&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: J M Brown, J A Greager, D G Pavel, T K Gupta
Journal: JNCI Journal of the National Cancer Institute (1985)

125I-labeled monoclonal antibody 19-24 (mouse isotype IgG1) was evaluated for its potential usefulness in the clinical radioimmunodetection of sarcoma. The antibody reacts with a cell surface antigen preferentially expressed in many human soft tissue and bone sarcomas. Chromatographic and electrophoretic analyses indicated that the labeled preparation was relatively pure. Binding studies in vitro demonstrated that specificity for antigen was retained after iodination and indicated that the labeled antibody possessed an immunoreactivity in excess of 90% and a binding constant of 8.1 X 10(9) M-1. When administered to athymic NCr-nu/nu mice bearing 1-cm diameter human fibrosarcoma HT-1080 xenografts, the labeled antibody preferentially localized in tumor deposits. Maximum tumor-to-blood radioactivity ratios (2.2-3.4) were obtained 7 days after antibody injection. Specificity of the localization was confirmed with a control mouse IgG1 antibody and by using a nonreactive xenograft. Distinct tumor images were obtained by gamma camera without the use of subtraction techniques, demonstrating the possible clinical utility of the labeled antibody.
Survival after Sublobar Resection for Early-Stage Lung Cancer: Methodological Obstacles in Comparing the Efficacy to Lobectomy
Authors: Emanuela Taioli, Rowena Yip, Ingram Olkin, Andrea Wolf, Daniel Nicastri, Claudia Henschke, David Yankelevitz, Harvey Pass, Raja M. Flores
Journal: Journal of Thoracic Oncology (2015)
Characteristics of a high-risk minority population
Authors: N. Jooma, R. Elledge, K. Sexton, M. Kalidas, M. Rimawi, C. Osborne, J. Chang
Journal: Journal of Clinical Oncology (2007)

21141 Background: Black and Hispanic breast cancer patients have a worse outcome when compared to Caucasians. This could be due to socioeconomic, cultural or biologic factors. We hypothesized that host and tumor biologic characteristics associated with a poor outcome may be found more often in minority women. Methods: Race/ethnicity, menopausal status, tumor histological features, and patient characteristics including age and body mass index (BMI) were reviewed from a prospective neoadjuvant trial of docetaxel vs. doxorubicin/cyclophosphamide at Baylor College of Medicine Breast Center, from September 2002 to September 2006. The data were analyzed using Chi-square and Fisher's exact tests, while the Kruskal-Wallis method was used to analyze BMI. Results: Of the 167 patients, 63% (n=105) were Caucasian, 15% (n=26) were Hispanic and 22% (n=36) were Black. The mean age was 47.6 years (range: 30–72). Fifty-nine percent were premenopausal. Overall, mean BMI was 29, with Caucasians having a mean BMI of 27.5, Hispanics with 29.8 and Blacks with a BMI of 34.6 (P&lt;0.001). Sixty-five percent of the Caucasians and 58% of Hispanics were ER+ or PR+ versus 44% of Blacks (P=0.09). Sixteen percent of Caucasians were HER-2 positive compared to 4% of Hispanics and 9% of Blacks (p=0.25). In addition, 22% of Caucasians and 38% of Hispanics were ER-, PR-, HER-2- compared to 50% of tumors from Blacks (p=0.007). There was a trend linking BMI and triple negative status in breast cancers, which did not achieve statistical significance (p=0.21). Conclusion: In this study we found that black and Hispanic women were more likely to be obese and have ER-, PR-, HER-2- tumor phenotypes, both of which have been associated with poorer outcomes. Ongoing studies are being performed to elucidate the link between clinical and biological characteristics and understand the underlying molecular mechanisms associated with these findings. No significant financial relationships to disclose.
A phase II trial of ketoconazole plus granulocyte/macrophage-colony stimulating factor (GM-CSF) in androgen independent prostate cancer (AIPC) patients (pts)
Authors: A. M. Lin, C. J. Ryan, J. Rosenberg, B. I. Rini, T. Nguyen, V. I. Weinberg, E. J. Small
Journal: Journal of Clinical Oncology (2005)

4614 Background: Ketoconazole (keto) produces serologic and objective responses in 30–50% of AIPC pts. However, response durations are typically short (median 5 months). GM-CSF is a pleiotropic cytokine that may enhance dendritic cell function in vivo. We hypothesized that GM-CSF may augment the efficacy of ketoconazole and tested the combination of keto and GM-CSF. Methods: Eligible pts had progressive AIPC and had received no prior immunotherapy. Pts received keto 400 mg po tid and hydrocortisone 20 mg po qam and 10 mg po qPM. GM-CSF 250 mcg/m2 was administered SQ on days 1–14 of each 28-day cycle. The study is powered to detect a 50% prolongation of the median response duration relative to historical controls (from 5 months to 7.5 months). Results: Twenty-six of 48 planned pts have been enrolled. The median age is 70 years (range: 60–84), and median PSA 26.9 ng/mL (range: 3.9–257.6). Eighteen pts had metastatic disease while 8 had PSA-only disease. The median treatment duration is 3.4 months (range: 0.5–7.2+). Eighteen pts have completed 3 treatment cycles and are deemed evaluable for response. Fourteen of these pts (78%) have experienced a PSA response by consensus criteria, associated with stable scans. For all 26 enrolled pts, the most common adverse event was grade(gr)1 local injection site reactions. Eight gr3 toxicities have occurred: 4 pts had gr3 fatigue, 2 pts experienced substernal chest pain attributed to bone marrow expansion (negative cardiac evaluation), and 1 pt each had gr3 dizziness and dyspnea. Other toxicities included 2 pts with gr2 transaminitis. Three pts have come off study, 2 for disease progression by scans and 1 for PSA progression. Two of these pts had disease progression while holding therapy for gr3 fatigue. Conclusions: The combination of keto and GM-CSF is relatively safe and well-tolerated in AIPC pts with a preliminary PSA response proportion of 78%. Longer follow-up is needed to determine the median duration of response. Accrual is ongoing. No significant financial relationships to disclose.
Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next generation sequencing.
Authors: Jane E. Churpek, Tom Walsh, Yonglan Zheng, Silvia Casadei, Anne M. Thornton, Ming K. Lee, Matthew Churpek, Dezheng Huo, Cecilia Zvosec, Fang Liu, Qun Niu, Jing Zhang, James Fackenthal, Mary-Claire King, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2013)

CRA1501 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Abstract P096: Association of Cystatin C Gene Cluster Variants with Cystatin C levels, Chronic Kidney Disease, and Risk of iIncident Cardiovascular Disease and Mortality
Authors: Adrienne Tin, Conall M O'Seaghdha, Qiong Yang, Ronit Katz, Yongmei Liu, Wen Hong Linda Kao, Caroline S Fox, Michael G Shlipak
Journal: Circulation (2012)

Background: Accounting for genetic variation in cystatin C production may improve glomerular filtration rate estimation (eGFR) and the classification of chronic kidney disease (CKD). As the majority of known SNPs influencing cystatin C tend to result in lower circulating levels, we hypothesized that accounting for genetic variation would result in higher eGFR calculated from cystatin C level (eGFRcys) and a lower prevalence of CKD. Furthermore, we hypothesized that adjusting eGFRcys for the genetic component would strengthen the associated cardiovascular and mortality risk estimates. Methods: Four prospective cohorts were included: the Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health ABC (HABC) studies. We developed a cystatin C genotype score using 7 SNPs within the cystatin gene cluster on chromosome 20, which accounted for 8% of the variability in eGFRcys in FHS. We compared the association of the cystatin C genotype score with cystatin and creatinine-based eGFR and CKD (eGFR &lt;60ml/min/1.73m2). We also tested whether eGFRcys, adjusted for the genotype score, resulted in a change in the prevalence of CKD. Finally, we performed longitudinal analyses of the genotype score, and both adjusted and unadjusted eGFRcys, with mortality and cardiovascular events. Results were combined using inverse-variance meta-analysis. Results: A total of 14,647 participants were included. A higher cystatin C genotype score was associated with lower cystatin C levels (beta-coefficient −0.45; p=4.0E−103) and higher eGFRcys (beta-coefficient 0.53; p=1.0E−95), and was not associated with creatinine-based eGFR (p=0.4). The absolute prevalence of CKDcys was 10.7%; after adjustment for the genotype score, the absolute prevalence of CKDcys was 8.9%, a difference of 1.8%. Adjustment for the genotype score had no impact on the association between eGFRcys with CVD events (HR 0.38 [95% C.I. 0.33–0.44] per unit of log(eGFRcys)) and mortality (HR 0.29 [95% C.I. 0.26–0.32] per unit of log(eGFRcys)). Conclusion: In general, adjusting for the genetic contribution of cystatin C levels resulted in higher estimated GFR and marginally fewer CKD cases. This indicates the presence of a genetic bias in circulating cystatin C levels; however, this does not appear to be of clinical importance with respect to cardiovascular and fatal outcomes.
Abstract 18512: Comparison of Carotid Intima-media Thickness, Plaque Score and Plaque Area Stenosis in Patients with Acute Myocardial Infarction with and without ST-segment Elevation
Authors: Sunyoung Park, Seung-Hwan Lee, Taeho Song, Hyunji Seo, Su-Yeon Lim, So Jin Kwon, Jun-Won Lee, Young-Jin Youn, Sung-Gyun Ahn, Byung-Su Yoo, Junghan Yoon
Journal: Circulation (2012)

Background: Increased carotid intima-media thickness (IMT) and presence of carotid plaques are being used for estimation of subclinical atherosclerosis but their role in established coronary artery disease remains uncertain. Therefore, we aimed to evaluate whether carotid parameters are correlated with extent and complexity of coronary atherosclerosis using SYNTAX score (SS). We also sought to compare carotid parameters between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Methods: Of 1351 patients who consecutively received carotid ultrasound evaluation from Sep 2011 to May 2012, 137 patients diagnosed with STEMI (n=73) and NSTEMI (n=65) were enrolled (104 men and mean age 64.9±12.7 years). IMT, plaque score (PS) and % plaque area stenosis (AS) were compared between STEMI and NSTEMI. PS was computed according to the presence of plaque in 4 different locations. For the quantification of plaques, % AS was calculated by the ratio of the luminal stenosis area divided by the vessel area at the narrowest portion in short axis view. Clinical parameters and SS were also compared. Results: The prevalence of hypertension and diabetes was higher in NSTEMI group than STEMI group (65.6% vs. 39.7%, p=0.002 and 42.2% vs. 19.2%, p=0.003). A higher incidence of multi-vessel disease (≥2 vessels) and diffuse lesion was observed in NSTEMI group (69.6% vs. 45.1%, p=0.007 and 65.6% vs. 46.6%, p=0.038). NSTEMI group had significant higher SS (16.0±9.2 vs. 20.0±10.2, p=0.015), IMT values, PS and % AS. SS was correlated with mean IMT values and PS (r=0.182, p=0.033 and r=0.200, p=0.019). SS was higher in NSTEMI patients with increased IMT &amp; plaque than those with normal carotid artery (22.2±9.9 vs. 10.3±6.1, p=0.001). Conclusion: NSTEMI was associated with increased CIMT, higher PS and % AS reflecting atherosclerotic burden. Carotid parameters provided additional information to predict the severity of coronary atherosclerosis in patients with NSTEMI.
Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition
Authors: S Köhrer, O Havranek, F Seyfried, C Hurtz, G P Coffey, E Kim, E ten Hacken, U Jäger, K Vanura, S O'Brien, D A Thomas, H Kantarjian, D Ghosh, Z Wang, M Zhang, W Ma, H Jumaa, K-M Debatin, M Müschen, L H Meyer, R E Davis, J A Burger
Journal: Leukemia (2016)
Reactivity of Human Lymphocytes Against Autochthonous and Allogeneic Normal and Tumor Cells &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ernest H. Y. Chu, Jan Stjernswärd, Peter Clifford, George Klein
Journal: JNCI Journal of the National Cancer Institute (1967)

Human peripheral lymphocytes from tumor-bearing and non-tumor-bearing patients were added to monolayer cultures of autochthonous and allogeneic normal or neoplastic cells in vitro with or without phytohemagglutinin (PHA). The normal cells were derived from skin, the tumor cells from postnasal carcinomas or sarcomas. The cultures were scored for clearly visible plaques in the monolayer. Without PHA, lymphocytes affected autochthonous skin target cells in 1 of 16 cultures. If PHA was added,the figure increased to nearly 50%(12/28). Whether this phenomenon is related to an autoimmune reaction or to some less specific effect of the PHA stimulus is unknown at present. In the absence of PHA, lymphocytes from African tumor-bearing hosts destroyed allogeneic skin fibroblasts in 4 of 14 cases, and lymphocytes from non-tumor-bearing Swedish donors showed this effect in 14 of 24 tests. The somewhat lower reactivity of the African lymphocytes was also apparent in other tests. It cannot be stated whether the difference was due to the tumor-bearing condition of the hosts or to some other differences involved in comparison of the two groups. Without PHA, lymphocytes of the African tumor patients destroyed their own autochthonous tumor cultures in 4 of 16 cases. Addition of PHA increased the proportion of positives to 20 of 28. A comparison with the corresponding figures for autochthonous skin cultures (1/16 and 12/28, respectively) indicates a relatively higher reactivity against the autochthonous tumor cells, both with and without PHA. This cannot be interpreted as a difference in target cell sensitivity to the same lymphocyte action, because no such difference was apparent when the sensitivity of skin and tumor to allogeneic lymphocytes was compared in the absence of PHA (4/14 and 4/14 with African lymphocyte donors; 14/24 and 14/24 with Swedish lymphocyte donors, respectively). The most probable explanation is that the antigenic barrier responsible for the lymphocyte effect is larger for tumor than for skin, or that the results reflect a presensitization of the tumor donor against its autochthonous neoplastic cells.
Factors associated with sedentary lifestyle of inpatients not restricted to bed
Authors: Daniel Souza, Fernando Wegner, Luciana Chiavegato, Adriana Lunardi
Journal: European Respiratory Journal (2014)

Prolonged stay on bed is related to the development of musculoskeletal and respiratory disorders. AIMS: To objectively assess the physical activity level and related factors of hospitalized patients without problems to walk. METHODS: This study enrolled 133 consecutive hospitalized patients (52.6% male; 48.3±16.7yrs old; 69.3±19.1Kg) for clinical or surgical reasons. Patients no restricting to walk with no neurological nor cognitive was included. Patients were evaluated about their clinical history, habits and addicts, anthropometry and level of physical activity. The physical activity level was evaluated by accelerometry around the waist during 24h per day, during 4 consecutive days. Multiple linear regressions were performed to data analyses. RESULTS: All patients spent most part of their time lying on the bed (3250±1872min, 94% of total time) and few time doing activity of moderate intensity (15±16min, 0.5% of total time). They spent a mean of 63.4±55.0 Kcals per day and walked 1586.58±1362.64 steps. The regression models show that age and weight were associated with inactivity (R2=0.50; p<0.05) and that the smoke habits and alcoholism and respiratory and musculoskeletal complaints were negatively associated with moderate activities (R2=0.63; p<0.05). The BMI, comorbidities and cancer were not associated with the physical activity level. CONCLUSIONS: Our finds show that inactivity is highly prevalent during hospitalization even for patients not restricted to bed. The factors associated with sedentary lifestyle are age, weight, smoke habit, alcoholism, respiratory and musculoskeletal complaints. These results should prompt for stimulating physical activity during hospitalization.
PTH-133 Understanding the care pathway of patients with cirrhosis in the last year of life
Authors: S Davis, J Low, V Vickerstaff, L Greenslade, K Hopkins, A Marshall, D Thorburn, L Jones
Journal: Gut (2015)

<h3>Introduction</h3> Liver disease is a growing global public health problem and the 5<sup>th</sup>largest cause of death in the UK. Health policy for this patient group primarily centres on prevention, paying minimal attention to improving end of life care for those affected. <h3>Aims</h3> To follow patients with cirrhosis in the last year of life, plotting healthcare use and identifying barriers to good end of life care. <h3>Method</h3> Retrospective review of purposively selected case notes (30 cirrhotic patients) referred to a tertiary London liver unit. Pathways of care were modelled, by combining clinical data and service utilisation information extracted from medical notes, and qualitative focus groups/interviews with 14 liver health professionals, about barriers to good end of life care. <h3>Results</h3> During the last 12 months of life medical crises often precipitated unplanned emergency admissions to hospital. Patients experienced high symptom burden and were repeatedly treated intensively to aid recovery. Although clinicians recognised that limited treatments and services exist to address patients’ problems, many continued to treat patients actively. Opportunities to initiate palliative care were documented but not always acted upon. Discussions were rarely held with patients about their future wishes; care planning conversations occurred late in the patient trajectory and were more likely to occur with the patient’s family. Specialist palliative care referral occurred within the last few days of life. <h3>Conclusion</h3> Clinicians have difficulties identifying when to initiate end of life care for patients with cirrhosis, when prognosis is uncertain and active treatment may afford a degree of short term recovery. Earlier integration of palliative care would facilitate care planning discussions and better inform patients and families of the choices available, in the knowledge they may be entering the dying phase. <h3>Disclosure of interest</h3> None Declared.
Primary Squamous Cell Carcinoma of Trachea Arising 4 Years After Radioiodine Treatment of Papillary Carcinoma of Thyroid
Authors: Teik Hin Tan, Boon Nang Lee
Journal: Clinical Nuclear Medicine (2016)

Primary squamous cell carcinoma (SCC) of the trachea is rare. Here, we presented a rare case of primary SCC of the trachea arising 4 years after radioiodine (RAI) treatment of papillary carcinoma of the thyroid. In this case, concomitant uptake of I-RAI and F-FDG was demonstrated in the thyroidal mass with tracheal invasion, which mimicked mixed well-differentiated and dedifferentiated thyroid carcinoma. The diagnosis of SCC of the trachea was made only after tracheal biopsy. This case illustrates that FDG-avid thyroid bed lesion, in the presence of thyroid carcinoma, may not necessarily be related to the thyroid pathology.
Long-term versus short-term androgen deprivation combined with high-dose radiotherapy for localized prostate cancer: A Spanish multicenter phase III trial.
Authors: A. Zapatero, A. Guerrero, X. Maldonado, A. Alvarez, C. González San Segundo, A. Cabeza, V. Macías, F. Casas, A. Pedro-Olivé, F. A. Calvo
Journal: Journal of Clinical Oncology (2010)

e15036 Background: Controversy remains about the timing and optimal duration of AD when associated to high- dose radiotherapy (HDRT). The purpose of this trial is to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) in the setting of HDRT. Methods: Patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high risk factors according to NCCN criteria and PSA less than 100 ng/ml were included. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (minimum dose to the prostate 76 Gy) before were they randomized to adjuvant AD (LTAD) with gosereline for two years. Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Primary endpoints were biochemical-disease free survival (bDFS) and toxicity scores. As approved by the study's Data and Safety Monitoring Committee an early interim analysis of compliance and safety is reported here. Results: To date, 298 men have been enrolled out of a planned accrual of 358 patients of whom 270 were valuable for the present analysis. One-hundred thirty four were randomly assigned to LTAD (69 HR and 65 IR) and 136 to STAD (71 HR and 65 IR), p=1.0. Demographic data, tumor and treatment characteristics were evenly distributed in the two arms. The median follow-up was 21 months. Relevant adverse reactions attributed to AD and RT grade > 2 late toxicity are summarized in the Table. Four patients in the STAD arm (2 IR and 2 HR) have developed biochemical failure compared to no one in LTAD arm. Conclusions: The interim analysis of this ongoing study shows that the present trial is safe and feasible. Adverse effects AAD arm non ADD arm p value Attributed to AD Osteoporosis 3% 0% NS Myocardial infarction 1% 0% NS Attributed to RT Frequency urinate 14% 15% NS Incontinence 3% 0% NS Hematuria 0% 3% NS Urethral estenosis 2% 0% NS Diarrhoea 0% 1% NS Proctitis 0% 3% NS Rectal bleeding 4% 4% NS Abbreviations: AAD, adjuvant androgen deprivation; NS, not significant. No significant financial relationships to disclose.
French drug trial had three major failings, says initial report
Authors: Nigel Hawkes
Journal: BMJ (2016)

Three major shortcomings have been identified in the drug trial that led to the death of a volunteer last month, the French health minister, Marisol Touraine, has said.

Administration of the drug being tested continued even after the first volunteer had fallen ill, Touraine said at a press conference on 4 February. This man, believed to be a 49 year old singer and artist from Brittany called Guillaume Molinet, had been given a dose of the drug on 7 January and admitted to hospital on the evening of 10 January. But on the morning of 11 January Biotrial, the French company carrying out the trial, administered the same dose to five more participants.

The second error was not to inform these volunteers of what had happened the previous evening, to give them the chance to withdraw their consent. 

The third had been not reporting the incident to the French national medicines safety agency (ANSM) until four days after the first volunteer had been admitted to hospital.

Touraine’s comments were based on a preliminary report from the French social affairs inspectorate (Inspection Generale des Affaires Sociales), …