tbuckley/cabot-search huggingface dataset:
Abstract LB-33: Identification of two unrecognized acute myeloid leukemia (AML) subtypes based on cell by cell analysis of leukemic blasts
Authors: Faye Hsu, Garry P. Nolan, Tiffany Chen, Yury Goltsev
Journal: Cancer Research (2012)

Abstract Single cell multiparametric flow cytometry studies have previously shown that G-CSF-mediated intracellular signaling responsiveness of blast cell subsets stratified clinical outcomes of AML patients. 13 AML samples were stimulated with G-CSF, fixed, and permeabilized with a technique we developed that preserves mRNA integrity in a manner suitable for microarray-based expression analysis. From the microarray profiles we identified surface markers that could be prospectively used to separately enrich G-CSF Responsive Cells (GRCs) and non-G-CSF Responsive Cells (NGRCs) from each sample. The results demonstrate that two previously unrecognized subtypes of AML could be discerned, as portrayed by the proteomic and molecular characteristics of the GRC and NGRC subsets. First, GRC cells had a higher colony formation capacity as well as being more reactive to cytokines secreted by NGRCs In one discovered AML subtype, patients present with bone marrow that had higher percentages of GRCs (20-50%), with the remainder being NGRCs. The molecular signatures of both the GRCs and NGRCs in this subtype had a hematopoietic progenitors mRNA signature (HPMS). In the second subtype of AML there were lower percentages of GRCs (0.5-10%, which had the HPMS) but in these cases the NGRC mRNA signatures were distinct resembling those of a more differentiated myeloid phenotype. Therefore, in most AML patients tested, two blast cell populations inevitably appear, and each of these blasts represented a distinct level of hematopoietic maturity, or cytokine responsiveness. The common thread between the two subtypes is that the GRCs in each patient were more capable of colony formation, enabled by a potentially more “stem-like” phenotype. Critically, each population would be clinically termed “blast” cells and would therefore be considered malignant and a potential target for chemotherapy. These results lead to two important conclusions. The first is that the blast phenotype can exist independently of the apparent cell maturation stage. This raises the questions of whether each blast subtype is equally susceptible to standard chemotherapy, whether a strategy of defining the molecular players that drive the formation of each of these blast types should be pursued, and finally whether such information can be used to better combat these aspects of the leukemic disease spectrum. 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 LB-33. doi:1538-7445.AM2012-LB-33
Ga-67 Uptake in Cutaneous Lesions of Graft-Versus-Host Disease
Authors: RODOLFO F. NUÑEZ, HENRY W. D. YEUNG, HOMER A. MACAPINLAC, HUGO CASTRO-MALASPINA, STEVEN M. LARSON
Journal: Clinical Nuclear Medicine (2000)

Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liver. A 47-year-old woman with fever of unknown origin was referred for a Ga-67 scan. The study showed diffuse uptake of Ga-67 throughout the skin. Subsequently, a skin biopsy confirmed the diagnosis of acute GVHD. The incidence, diagnosis, and pathophysiology of the dermatitis in acute GVHD are discussed.
Multidisciplinary laparo-endoscopic management of a subcardial gastric diverticulum
Authors: B. Globke, P. Fikatas, A. Beck, A. Adler, S. Schmidt
Journal: Endoscopy (2013)

A 46-year-old obese female patient presented in the emergency room with acute exacerbation of abdominal pain, recurring nausea and vomiting, and a history of chronic pain in the lumbar spine. An external report of recently taken magnetic resonance images described a suspicious left adrenal mass ([Fig. 1]). The patient also had reflux symptoms and fetor ex ore. A history of rapid weight loss of 16 kg over the past 3 months and increasing fatigue raised suspicion for malignant disease. Assessment for pheochromocytoma was negative. A computed tomography (CT) scan excluded any malignancy and showed subcardial pouching of the dorsal gastric wall ([Fig. 2]). Oral contrast swallow ([Fig. 3]) and endoscopy confirmed the diagnosis of a gastric diverticulum with an aperture of 35 mm, filled with food remnants. Due to the clinical relevance of this benign finding, the patient was referred to general surgery. Using an endoscopic rendezvous technique, laparoscopic resection was carried out with an EchelonFlex60 Endopath Stapler (Ethicon Endo-Surgery, Cincinnati, Ohio, USA) under visual control from both sides of the diverticulum ([Fig. 4]). Histologic examination showed a full-thickness stomach specimen with slight chronic inflammation of otherwise normal gastric mucosa, indicative of a congenital diverticulum. Both the fetor and reflux symptoms ceased immediately after the surgery. A second contrast swallow on postoperative day 5 showed a patent suture and the patient was discharged thereafter.
Telephone disclosure of <i>BRCA1/2</i> test results: a survey of genetic counselors.
Authors: AR Bradbury, L Patrick-Miller, SA Cummings, D Fetzer, M Daly
Journal: Cancer Research (2009)

Abstract Abstract #1098 Disclosure of BRCA1/2 test results has historically been conducted in person by a certified genetic counselor (GC) and/or other health care professional. Due to increasing demand for and access to BRCA1/2 testing, there has been interest in providing genetic counseling services, including disclosure of test results, by telephone and internet. The practice of telephone disclosure among certified genetic counselors has not been described. We conducted semi-structured interviews with GCs to determine current prevalence of, and future interest in, telephone disclosure (TD) of BRCA1/2 test results. Surveys were self-administered and completed via a secure web site. Participants were recruited through the NSGC Cancer Special Interest Group. 195 GCs completed the survey (25% response rate). 23% of respondents have provided pre-test counseling by telephone. 98% reported having provided genetic test results by telephone, although many (48%) conduct TD rarely (&amp;lt;25% of the time). 33% reported TD experiences that had made them question TD as a practice. Comfort with TD varied by test result (37% comfortable with TD for positive test results, 77% for true negative results, 49% for indeterminate results and 33% for VUS results). The majority of GCs do not include a physician (85%) in the TD. Many report encouraging in-person follow-up with a GC (44%) and/or physician (30%). Overall, 42% reported being very interested in TD and 73% felt TD could be an acceptable standard practice. These results suggest many genetic counselors have provided genetic test results by phone and are interested in including telephone disclosure of BRCA1/2 test results in their practice. Given provider interest and the expansion of testing for BRCA1/2 and other hereditary cancer syndromes, further research evaluating the cognitive, affective and behavioral responses to telephone disclosure is warranted. Understanding the impact of telephone disclosure on factors such as, comprehension, risk perception, communication and performance of risk reducing behaviors and their mediators will be critical for the development of telephone disclosure policy and procedures that will optimize adaptive responses to receiving genetic test results via telephone or internet. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1098.
Changing Normal Values for Thyroidal Radioiodine Uptake
Authors: James A. Pittman, George E. Dailey, Richard J. Beschi
Journal: New England Journal of Medicine (1969)

Determinations of 24-hour thyroidal radioiodine uptake were made on 63 euthyroid subjects in 1959 and by the same method on 53 euthyroid subjects in 1967–68. The uptake was 28.6 ± 6.5 per cent in 1959 and 15.4 ± 6.8 per cent in 1967–68 (mean ± S.D.). The low values currently seen reflected a large intake of iodine in the subjects, who displayed elevated urinary iodine excretions and plasma inorganic iodide concentrations, and depressed thyroidal iodide clearances. Food analyses revealed the diet to be very rich in iodine, and bread to be a major contributor of this substance to the diet. Further investigation showed that the process used for the commercial manufacture of bread was changed in the interval between the two studies and that the present method includes large quantities of iodine. About half the commercial white pan bread in the United States is now made by this process.
P21 Long Term Antifungal Treatment (LTAFT) is Effectively Associated with Improvement in Health Status (HS) in Patients with Chronic Pulmonary Aspergillosis (CPA)
Authors: KA Al-shair, MK Kirwan, GA Atherton, AC Caress, DWD Denning
Journal: Thorax (2012)

<h3>Introduction</h3> CPA is a chronic progressive respiratory infectious disease results in significant lung tissue destruction with a 50%+ 5 year mortality. Response to antifungal therapy is slow, with ∼80% of patients who respond doing so by 6 months. We recently demonstrated the reliability and validity of SGRQ in examining HS in CPA (Chest, in press), and now present longitudinal data on the efficacy of LTAFT in improving HS in CPA patients. <h3>Method</h3> HS of 98 CPA patients were assessed 3 times over 6 months using the well-established standardised SGRQ. CPA severity was assessed using our published CPA banding system. FEV1, BMI, dyspnoea (using MRC dyspnoea scale) were measured. <h3>Results</h3> Mean age was 58 years and 48% were female; and 25, 58 and 15 had band 1, 2 and 3 CPA respectively. At visit 2 and 3 (V2 and V3), we found that overall total and domain SGRQ scores were either lower (improved health status) or similar compared to V1 (table 1). Categorizing the cohort by those who reported improvement or deterioration by a total SGRQ score of ≥4 at V3 comparing to V1, we found that 43% improved, 22% remained stable and 35% deteriorated. The median (IQR) of total SGRQ score of the improved group at V3 was 58 (42–66) compared to 71 (60–79) at V1; and for the deteriorated group was 67.5 (57–76) at V3 compared to 62 (41–67)) at V1. The deteriorated were older (62 (9.8) years versus 56.1 (9.3) (p=0.008); and tended to have lower BMI, more dyspnoea and worse lung function. Moreover, binary regression multivariate analysis showed that age maintained its association with deterioration in HS (OR 1.13, 95% CI 1.01–1.26, p=0.03) after correcting for gender, BMI and FEV<sub>1</sub>%. Of the 37 patients started on an antifungal agent at V1 who took it for 3+ months (including a 3 week IV course of amphotericin B), 22 (59%) improved, 11 (30%) were stable and 4 (11%) deteriorated at V3. <h3>Conclusion</h3> LTAFT prevented/reduced the progression of CPA and patients preserved overall good HS. More therapeutic approaches for this progressive disease are urgently needed.
Abstract P6-01-09: HER4 Is Downregulated in Lymphnode Metastases Compared to the Paired Primary Breast Carcinoma
Authors: A Brügmann, V Jensen, JP Garne, E Nexo, B. Sorensen
Journal: Cancer Research (2010)

Abstract Introduction: The Human Epidermal Growth Factor Receptor 4 (HER4) of the EGF receptor family has been characterized in both normal and malignant human breast tissue and HER4 overexpression has been shown to predict prolonged survival compared to HER4 receptor negative disease. In our study we investigated the HER4 expression in normal breast tissue, primary breast carcinoma and in ipsilateral metastatic axillary lymphnodes at the time of primary breast cancer surgery. Material and methods: Paired tissue samples from normal breast tissue and primary breast carcinomas were obtained from 169 patients. Out of these a third sample was obtained from 66 patients with metastatic lymphnodes. The primary tumour specimens were sampled uniformly at random. The mRNA expression of HER4 was quantified with real time RT-PCR and expressed relative to the householdgene (HMBS) in arbitrary units (arb.u.). Results: The mRNA expression of HER4 was significantly higher in breast carcinoma with a mean of 2.26 arb.u. [95% c.i.:1.87 to 2.65 arb.u.] than in the paired sample of normal breast tissue with a mean of 0.82 arb.u. [95% c.i.: 0.47 to 1.16 arb.u.] (p=0.0001). The mRNA expression of HER4 was also significantly higher in breast carcinoma than in the corresponding lymphnode mean 0.75 arb. u. [95% c.i.: 0.43 to 1.07 arb.u.] (p=0.015). There was no significant difference observed in mRNA expression of HER4 between the metastatic lymphnode and the corresponding normal breast tissue (P&amp;gt;0.05). When HER4 expression was compared between the primary tumours that had metastasised and those that had not, there was no significant difference (P&amp;gt;0.05). Conclusion: The HER4 expression was high in the primary tumour as compared to normal breast tissue and the corresponding lymphnode. In view of previously published relations between a low expression of HER4 and a poor prognosis our results warrant further studies in order to evaluate whether suppression of HER4 in tumour cells could be involved in lymphogenic metastatic spread. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-09.
Abstract 1922: Ethnic and racial differences in colorectal cancer
Authors: Michael S. Simon, Cynthia A. Thomson, Erin Pettijohn, Ikuko Kato, Rebecca Rodabough, Dorothy Lane, F Allan Hubbell, Mary Jo O'Sullivan, Lucille L. Adams-Campbell, Charles P. Mouton, Judith Abrams, Rowan T. Chlebowski
Journal: Cancer Research (2011)

Abstract Introduction: The Women's Health Initiative (WHI) provides a robust database to determine whether differences in known colorectal cancer (CRC) risk factors influence ethnic and racial differences in incidence and mortality. Methods: The WHI is a multi-center longitudinal study of postmenopausal women age 50-79 years recruited from 40 centers across the US. Baseline self-administered questionnaires were used to collect self-identified ethnicity or race, other demographics and health status. Cancer screening information was collected annually and cancer diagnoses were centrally adjudicated. Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by ethnicity/race. Results: The ethnic and racial composition of the sample is 131,481 (84%) White, 14,323 (9%) African American (AA), 6,362 (4%) Hispanic, 694 (&amp;lt;1%) Native American and 4,148 (3%) Asian/Pacific Islander (API). After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was highest among AA (annualized percent 0.14%), followed by Whites and Native Americans (0.12% each), API (0.10%) and Hispanics (0.08%). After adjustment for age and cohort assignment, Hispanics had a lower risk of CRC compared to Whites, HR 0.73 (95% CI: 0.54-0.97) (p=0.03), and AA had a marginally greater risk, HR 1.16 (95% CI: 0.99-1.34), p=0.06. Adjustment for other covariates, eliminated the difference in incidence between AA and Whites (HR 0.99, 95% CI: 0.82-1.20), however the difference in incidence between Hispanics and Whites increased (HR 0.68, 95% CI: 0.48-0.97), p = 0.03. Conclusions: Differences in CRC risk between Hispanics and Whites are not explained by sociodemographic or behavioral factors in the WHI cohort. 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 1922. doi:10.1158/1538-7445.AM2011-1922
OC-066 The Cancer Research UK (Cruk) Funded ICGC Oesophageal Adenocarcinoma Project: MRC Research Centre and Cruk Cambridge Research Institute
Authors: JMJ Weaver, N Shannon, C Ross-Innes, A Lynch, T Forshew, M Barbera, C-A Ong, P Lao-Sirieix, M Dunning, L Smith, M Smith, B Carvalho, M O’Donovan, T Underwood, M Murtaza, A May, N Grehan, R Hardwick, J Davies, A Oloumi, S Aparicio, N Rosenfeld, M Eldridge, C Caldas, P Edwards, S Tavare, R Fitzgerald
Journal: Gut (2013)

Introduction Esophageal adenocarcinoma (EAC) has one of the fastest rising incidences of any cancer in the western world. With a 5-year survival below 10% it is one of the most common causes of cancer death in US and UK. Currently little is understood about the genetic alterations that drive the development of OAC. Better understanding of these alterations may allow the development of novel therepeutic approaches Methods We have performed whole genome sequencing on 22 cases. Targeted amplicon resequencing of 27 recurrently mutated genes was performed on a validation cohort of 100 further oesophageal adenocarcinomas. Results In the discover set of 22 OACs we identified recurrent mutations (>3 tumours) in 31 genes including several implicated in tumorigenesis; TP53, CDKN2A, ARID1A. Strikingly in the validation cohort we observed that > 30% of EAC samples harbour mutation of one or both of the SWI/SNF complex members ARID1A and SMARCA4. In addition we identified highly recurrent mutations in several additional genes including TRIM58, SSTR4 and MYO18B. Conclusion Whole genome sequencing provides an unbiased screen of mutational architecture of OAC. This has allowed the identification of several recurrently mutated genes not previously implicated in this disease providing a unique insight to it’s pathogenesis Disclosure of Interest None Declared
Abstract 3717: Pigment epithelium-derived factor prolongs survival and enhances the <i>in vivo</i> antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer
Authors: Stephanie Filleur, Natalie Pardue, Katherine Rinard, Jessica Gillen, Thomas Nelius
Journal: Cancer Research (2012)

Abstract Background: The development of metronomic/low-dose administration of conventional chemotherapeutic drugs has recently shown great promise in the treatment of castration-refractory prostate cancer (CRPC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which has been shown to be down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF could enhance the cytotoxic effects of low-dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human CRPC PC3 and CL1 cell lines were genetically modified to stably co-express the fluorescent DsRed Express protein with PEDF. Resulting cell lines were characterized in vitro for PEDF expression by Western blot and for proliferation by growth curves and clone formation in Matrigel. PEDF anti-tumor effects were assessed on established subcutaneous xenografts in mice treated with Doc (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg ip every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells, pre-mixed with 50nM hr-PEDF or carrier control, into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits the proliferation and induces the differentiation of all CRPC cells tested in vitro. Similarly, PEDF expression decreases the development of subcutaneous PC3 and CL1 tumors in immune-compromised mice by 85% and 70%, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxic effects of low-dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for both PC3 and CL1). Conclusions: This data reinforces the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low-dose Doc and CTX chemotherapies. 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 3717. doi:1538-7445.AM2012-3717
Abstract A11: Phase II trial of letrozole (L), cyclophosphamide (C) and sorafenib (S) as neoadjuvant therapy in breast cancer patients (BC): Pharmacokinetic (PK) and pharmacodinamic (PD) analysis
Authors: Letizia Bazzola, Chiara Foroni, Daniele Andreis, Francesco Ferrozzi, Luigi Dogliotti, Alfredo Berruti, Stephen B. Fox, Adrian L. Harris, Daniele Generali, Alberto Bottini
Journal: Clinical Cancer Research (2010)

Abstract Introduction: This trial assessed the PK and PD of letrozole-cyclophosphamide-sorafenib combination as neoadjuvant setting in patients (pts) with operable breast cancer (BC). Methods: 13 estrogen receptor-positive postmenopausal BC pts with T2-4 N0-1 were enrolled to receive oral letrozole (L) 2.5 mg daily, 50 mg daily metronomic cyclophosphamide (C) and 400 mg twice daily sorafenib (S). S was introduced after 6 days of LC therapy. For PK analysis blood samples were collected on day 5 of cycle 1 and on day 1 of cycle 2 (day 29). At basal time and after 14 days, tumour size evaluation, Ki67 expression and MRI were performed. Results: A significant reduction in Ki67 expression was observed in all the 13 patients after 14 days only (median 20.7% (range 3-36%) and 9.75% (range 0-20%) at 15th respectively, p&amp;lt;0.0001) with a concomitant reduction in tumour size detected by MRI (median 37 mm (range 15-90 mm) and 31 mm (range 13.4-90 mm) respectively, p=0.047). Three patients attained a partial response at MRI (RECIST criteria) after 15 days. The changes in ki67 expression did not correlate with changes in tumor size evaluated by MRI (Spearman r: −0.37). 10 patients out of 13 showed a clinical complete response at the end of the treatment. The most common drug-related grade 2 (G2) adverse events were skin rush (46%), hand-foot syndrome (46%), anorexia (38%), fatigue (15%), and G3 diarrhea (23%). Mean plasma concentrations of C were consistently lower following concomitant administrations of L, S and C compared to administration of L and C. This trend was confirmed by the comparison of corresponding AUC (0-24) and Cmax values from Day 5, Cycle 1 and Day 1 of Cycle 2. No influence was detected by co-administration with L. Conclusions: These toxicity and PK results indicated that the combination feasible but sorafenib interpheres in non significant manner with the bioavailability of C. Moreover, the PD data indicated that the association of the already tested LC combination (Bottini at al, JCO 2006) with S is promising. A randomised study of LC vs LCS is ongoing. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A11
Characterization of t(12;21) breakpoint junctions in acute lymphoblastic leukemia
Authors: MT Andersen, I Nordentoft, LL Hjalgrim, CL Christiansen, VD Jakobsen, H Hjalgrim, N Pallisgaard, HO Madsen, M Christiansen, LP Ryder, N Clausen, P Hokland, K Schmiegelow, M Melbye, P Jørgensen
Journal: Leukemia (2001)