tbuckley/cabot-search huggingface dataset:
Mutations in RNA Splicing Machinery in Human Cancers
Authors: Benjamin Ebert, Olivier A. Bernard
Journal: New England Journal of Medicine (2011)

Massively parallel sequencing of cancer genomes is revealing a panoramic view of the genetic drivers of human neoplasms. In this issue of the Journal, Wang et al.1 describe an analysis of the coding sequences of samples from 91 patients with chronic lymphocytic leukemia. The disease is characterized by the accumulation of mature B lymphocytes, and its genetic basis is being rapidly elucidated.2,3 Wang et al. leveraged the large number of samples studied to identify sets of genes that are critical to the development of chronic lymphocytic leukemia. By sequencing both the malignant lymphocytes (CD19+CD5+) and matched nonmalignant control DNA . . .
Abstract PL01-01: The genetic basis for cancer therapeutics
Authors: William R. Sellers
Journal: Cancer Research (2012)

Abstract Cancer is a disease driven by the acquisition and clonal selection of gain- and loss-of-function genetic alterations. While a fuller understanding of the pattern, specificity and biological consequences of such genetic events remains for us to elucidate, it is now clear that therapeutics directed against the genetic underpinnings of cancer have had a marked clinical impact. The growing list of therapeutics with efficacy in defined genetic settings includes imatinib in BCR-ABL driven CML, trastuzumab in HER2+ breast cancer, and erlotinib and gefitinib in EGFR mutated lung cancer among others. Indeed, the efficacy of small molecule inhibitors of KIT, PDGFR, HER2, EGFR, BRAF and ALK in a diversity of malignances including GIST, lung cancer and melanoma support the notion that a new generation of efficacious drugs is emerging. Nonetheless, we can articulate 5 key road-blocks to the more rapid and widespread application of the “genetic paradigm” including 1) an incomplete understanding of the genetic alterations characteristic of human cancer; 2) the difficulty in developing therapeutics that reverse the activity of non-kinase oncogenes (e.g. RAS and MYC) or reverse the consequences of tumor suppressor mutations (e.g. p53, RB1); 3) the development of resistance to genetic targeted therapy; 4) the need to identify highly active novel combination therapy regimens and 5) the lack of a robust pre-clinical translational infrastructure allowing for the more accurate prediction of human clinical trial results. This lecture will discuss strategic approaches to these 5 problems in the context of novel emerging therapeutics. 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 PL01-01. doi:1538-7445.AM2012-PL01-01
AB0739 Infrared thermography of big toe in raynaud’s phenomenon
Authors: M. J. Lim, S. R. Kwon, K. H. Jung, K. Joo, S.-G. Park, W. Park
Journal: Annals of the Rheumatic Diseases (2013)

A collaborative, population based, prospective register study on the incidence of visual impairment in children during the year 1993 was carried out in five Nordic countries with a total population of 17 million inhabitants. The child population was 3.8 million individuals aged 0-17 years. The following variables were taken into account: nationality, age, sex, diagnoses, aetiology, degree of visual impairment, and additional impairments. Classification routines from an earlier prevalence study were used. The present study included 304 children corresponding to an incidence of notification of 8/100,000 children, varying from 5.7 to 11.1 in the five countries. Fifty per cent of the visually impaired children were reported before they were 3 years of age. In approximately 45% of the children, visual impairment was due to various brain disorders, with cerebral amblyopia and secondary optic atrophy as the two leading causes. The relative impact of retinopathy of prematurity had decreased from the third most frequent cause (10%) in the prevalence study to seventh place (4%) in the incidence study. Two thirds of the children had additional impairments and these children also suffered from the most severe visual impairments. Among aetiological factors the majority (64%) were prenatal. The overall male:female ratio of 1.4:1 was identical to the sex ratio of the prevalence study.
Abstract LB-441: The genome wide gene-environment interaction analysis for asbestos exposure on lung cancer susceptibility
Authors: Sheng Wei, Li-e Wang, Michelle K. McHugh, Younghun Han, Christopher I. Amos, Margaret R. Spitz, Momiao Xiong, Qingyi Wei
Journal: Cancer Research (2011)

Abstract Asbestos exposure is a known risk factor for lung cancer. Although recent genome wide association studies (GWAS) have identified a few novel loci for lung cancer risk, little is known about genome wide gene-environment interactions and lung cancer risk. To determine genetic variations involved in the interactions of gene-asbestos exposure on lung cancer risk, we conducted genome wide gene-environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using the Texas lung cancer GWAS dataset. This dataset included 307,870 SNPs from 1,154 lung cancer cases and 1,137 cancer-free controls. The initial SNP-level p values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models adjusted for age, sex, smoking status and pack-years. The p value for the most significant SNP rs12706823 was 1.37 × 10–4 and did not reach the genome-wide statistical significance. Using a versatile gene-based test approach to estimate the interactions at the gene level, we found the top significant gene was RNF121and was located on 11q13.4 (p value = 4 × 10–4). Interestingly, most of the genes with top significant p values were located in 11q13. When we used an improved gene set enrichment analysis approach (i-GSEA), however, we found a total of 249 pathways containing 16,079 genes, of which the Fas signaling pathway was the most significant pathway, significantly involved in the interactions between genetic variations and self-reported asbestos exposure (nominal p value &amp;lt; 0.001; false discovery rate (FDR) &amp;lt; 0.05). We believe our analysis is the first to comprehensively describe the genome wide gene-asbestos exposure interaction on lung cancer risk at the levels of SNPs, genes and pathways. Our findings suggested that the current designed GWAS may have a limited power to detect gene-environment interactions at the SNP or gene levels, but the pathway-based approach may be more powerful in performing genome wide gene-environment analyses. (This study was supported by NIH grants R01 ES 11740, R01CA 131274, R01CA055769, R01CA127219, R01CA121197 and P30CA016672) 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 LB-441. doi:10.1158/1538-7445.AM2011-LB-441
Multicenter international phase II study of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination in HER2-positive metastatic breast cancer (MBC): updated results with a longer follow-up.
Authors: A Chan, V Ganju, D Becquart, P Conte, L Petruzelka, M Gil-Gil, M Morand, N Vaissiere, G Villanova, N Tubiana-Mathieu
Journal: Cancer Research (2009)

Abstract Abstract #3151 Background: CT plus H is the standard treatment for HER2-positive MBC. Combination therapy of H plus vinorelbine is an active and safe regimen in this setting. The all-oral combination of NVBo and X has been reported as an active and safe regimen in many different trials in MBC. We report efficacy and safety information from an updated analysis of all 50 patients (pts) included in this trial, with a median follow-up of 28.5 months.&amp;#x2028; Methods: Main eligibility criteria included: HER2-positive disease (defined as IHC 3+ or FISH+), documented measurable metastatic disease previously untreated by CT, relapse ≥ 6 months after the end of neoadjuvant or adjuvant CT, Karnofsky PS ≥ 70. NVBo was given as at a dose of 80 mg/m2 (after a first cycle at 60) D1 and D8 every 3 weeks, X at 1000 (750 if ≥ 65 years) mg/m2 bid D1-D14 every 3 weeks, H at 4 mg/kg on D1 as a loading dose then 2 mg/kg i.v. weekly starting on D8. Treatment was continued until progression.&amp;#x2028; Results: Median age: 53.5years (18% ≥ 65); prior (neo)adjuvant CT 27 pts (54%); visceral involvement 41 pts (82%), &amp;gt; 2 metastatic sites 17 pts (34%); Median number of cycles: 10 (range 1-56); Median relative dose intensity: NVBo 75%, X 77%, H 96%; NVBo escalated to the recommended dose of 80 mg/m2 in 84% of pts; G3/4 NCI CTC v2 adverse events per pt: (n=49) neutropenia 69%, (n=50) febrile neutropenia 8%, infection without neutropenia 4%, stomatitis 4%, nausea 4%, vomiting 12%, diarrhea 16%, hand-foot syndrome 20%, asthenia 8%, LVEF decline 6%, alopecia (grade 2) 14%; Efficacy (n=44 evaluable patients): objective response rate (RECIST) 77% (95% CI [62-89]), CR 18%, PR 59%, SD 18%, PD 5%, disease control (CR+PR+ SD ≥6 months) 93% (95% CI [81-99]), median duration of response was 14.3 months (95% CI [9.8-16.8]), median progression-free survival was 12.8 months (95% CI [10.8-16.9]), overall survival results are not mature yet. Treatment is ongoing in 5 pts.&amp;#x2028; Conclusion: The combination of NVBo and X + H has shown high antitumoral efficacy in pts with HER2-positive MBC. Toxicity profile was acceptable with, in particular, a very low rate of alopecia. An efficacy and safety analysis in pts aged &amp;lt; vs ≥ 65 years will be performed and presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3151.
AB1015 Ultrasound Features of Synovitis and Tenosynovitis in Patients with Systemic Lupus Erythematosus
Authors: S. Monov, R. Shumnalieva, D. Monova, R. Nestorova, R. Rashkov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Involvement of musculoskeletal system in Systemic lupus erythematosus (SLE) includes the presence of arthralgias, deforming arthritis, usually with a non-erosive (Jaccoud9s) pattern and tenosynovitis. In a small percentage of patients there can be erosive features and synovitis indistinguishable from an inflammatory condition such as rheumatoid arthritis. Ultrasound technics offer the possibilities for detecting inflammatory changes even in an asymptomatic joints or periarticular tissues. <h3>Objectives</h3> To compare the data obtained by Power Doppler ultrasound (PDUS) measurements of the wrists, small joints and tenosynovial compartments of the hands and feet with the clinical and laboratory data in patients with SLE. <h3>Methods</h3> Fifthy-six SLE patients were included in the study. In all of them ultrasound examination on the wrists, small joints and tenosynovial compartments of the hands and feet including PDUS was performed. The patients were divided into two groups: group A (30 pts) presenting with arthralgias/arthritis and/or tenosynovitis and group B (26 pts) without musculoskeletal complains. Detection of inflammation included assessment of parameters as joint effusion (JE), synovial hypertrophy (SH) and grading the local pathological vascularization by PDUS on a semi-quantitative scale from 0 to 3. All patients underwent clinical examination, as well as laboratory measurements: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ANA, ENA, aPL, C3, C4. The disease activity was measured by SLEDAI -2K. <h3>Results</h3> PDUS data suggesting inflammatory conditions were established in 83,33% of the patients with clinical apparent articular or periarticular involvement (group A) and in 19,23% of the asymptomatic patients (group B). There was low correlation between the PDUS data for arthritis/tenosynovitis and SLEDAI-2K. No correlation was found between PDUS findings and the immunological activity. <h3>Conclusions</h3> Assessment of synovial inflammation including subclinical synovitis by PDUS parameters appears to be a promising sensitive method for detecting and monitoring the inflammatory activity in patients with SLE. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4556
Two Cases of Gastroesophageal Achalasia Detected by Radioiodide or Pertechnetate Imaging
Authors: R M Sherigar, J D Slavin, H B Hawkins, R P Spencer, M N Lassman
Journal: Clinical Nuclear Medicine (1998)

Considerable substernal activity was revealed during thyroid imaging (I-123 sodium iodide and Tc-99m pertechnetate) of two women. This activity did not clear completely on swallowing water, and achalasia was suggested. This was confirmed in both cases by radiographs after ingestion of contrast material. The differential diagnosis of substernal activity on these scans includes ectopic thyroid, vascular masses, and achalasia.
Ga-67 SPECT in Primary Tumors of the Head and Neck
Authors: Ken Motoori, Shigeo Yasuda, Koichi Nakano, Takashi Uno, Kouichi Isobe, Hisao Itoh
Journal: Clinical Nuclear Medicine (2002)

MOTOORI, KEN M.D.; YASUDA, SHIGEO M.D.; NAKANO, KOICHI M.D.; UNO, TAKASHI M.D.; ISOBE, KOUICHI M.D.; ITOH, HISAO M.D. Author Information
P2-18-03: Systemic Adjuvant Treatment of T1a and T1b N0M0 HER2+ Breast Carcinomas; an AERIO/UNICANCER Study.
Authors: J Peron, Y Vano, J-S Frenel, J Wassermann, L Albiges, MJ Rodrigues, PH Cottu
Journal: Cancer Research (2011)

Abstract Background: Trials have shown benefit of adjuvant trastuzumab (TZM) for node-positive (N+) or T1c+ HER2−positive breast carcinomas. Methods: Retrospective series in 6 french cancer centers from 2000 to 2010 of T1abN0M0 HER2 positive breast carcinomas. Multifocal tumors were excluded. Results: Two hundred five N- cases were retrieved. Median size was 8 mm (range, 2 to 10 mm), 51 were T1a (25%), 152 tumors were T1b; 120 tumors (59 %) exhibited significant hormonal receptors (HR) expression. All patients had surgery, 65 % (n= 133) had a local irradiation. Ninety percent of HR+ patients (108/120) received hormonotherapy: 77 received aromatase inhibitors (AI) upfront or sequential; 23 received tamoxifen (TAM) alone 13 received LHRH agonists alone or in combination with TAM or AI. Forty-nine percent (n= 101) had chemotherapy (CT) (Anthracycline alone for 41 cases, taxane alone for 31 cases, sequential A/T for 28 cases and concurrent for 1 case), associated with TZM in 90 cases. TZM was administered without chemotherapy in 3 cases. Decision of adjuvant CT and/or TZM was associated with (all p&amp;lt;0.05) HR-negative status, Elston-Ellis grade 2/3 and high mitotic index (MI) while patients with HR+/ low MI tumors were rarely treated (p&amp;lt;0.01). With a 41 months median follow-up, there was a statistically significant difference in invasive recurrences between TZM treated patients and others (log-rank test p=0.04). Twelve of the 112 patients treated without TZM (11%) had a recurrent invasive disease including 6 metastatic cases and 3 fatal events. There was one invasive recurrence in TZM group. There were as much recurrences in T1a as in T1b tumors. Three of the 12 recurrences (25%) in the group without TZM occurred in T1a cases. Conclusion: T1abN0M0 HER2 positive tumors have a significant risk of recurrence which could be avoided by adjuvant chemotherapy associated with TZM. Interestingly, there were no differences in the risk of recurrence between T1a and T1b. Adjuvant chemotherapy associated with TZM should not only be discussed in T1bN0 HER2−positive tumors but also in T1aN0 HER2−positive cases. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-03.
P0213 : Diabetes is a major determinant for refractory ascites in patients with cirhosis and is associated with hepatic microcirculatory changes
Authors: L. Elkrief, S. Buyse, X. Panhard, C. Baudry, R. Moreau, P.-E. Rautou, J. Belghiti, F. Durand, P. Bedossa, D. Valla, V. Paradis
Journal: Journal of Hepatology (2015)
Glycosylated Hemoglobin and the Risk of Microalbuminuria in Patients with Insulin-Dependent Diabetes Mellitus
Authors: Andrzej S. Krolewski, Lori M.B. Laffel, Martin Krolewski, Maryanne Quinn, James H. Warram
Journal: New England Journal of Medicine (1995)

The risk of microalbuminuria in patients with insulin-dependent diabetes mellitus (IDDM) is thought to depend on the degree of hyperglycemia, but the relation between the degree of hyperglycemia and urinary albumin excretion has not been defined.We measured urinary albumin excretion in three random urine samples obtained at least one month apart from 1613 patients with IDDM. Microalbuminuria or overt albuminuria was considered to be present if the ratio of albumin (in micrograms) to creatinine (in milligrams) was 17 to 299 or > or = 300, respectively, for men and 25 to 299 or > or = 300, respectively, for women. Measurements of glycosylated hemoglobin (hemoglobin A1) obtained up to four years before the urine testing were used as an index of hyperglycemia. Twelve percent of the patients had overt albuminuria and were excluded from subsequent analyses.The prevalence of microalbuminuria was 18 percent in patients with IDDM. It increased with increasing postpubertal duration of diabetes and, within each six-year interval of disease duration, it increased nonlinearly with the hemoglobin A1 value. For hemoglobin A1 values below 10.1 percent, the slope of the relation was almost flat, whereas for values above 10.1 percent, the prevalence of microalbuminuria rose steeply (P < 0.001). For example, as the hemoglobin A1 value increased from 8.1 to 10.1 percent, the odds of microalbuminuria increased by a factor of 1.3, but as the value increased from 10.1 to 12.1 percent, the odds were increased by a factor of 2.4.The risk of microalbuminuria in patients with IDDM increases abruptly above a hemoglobin A1 value of 10.1 percent (equivalent to a hemoglobin A1c value of 8.1 percent), suggesting that efforts to reduce the frequency of diabetic nephropathy should be focused on reducing hemoglobin A1 values that are above this threshold.
Abstract P2-17-01: Phase II Study of Bevacizumab in Combination with Docetaxel and Capecitabine for the First-Line Treatment of Patients with Locally Recurrent or Metastatic Breast Cancer
Authors: A Musolino, G Bisagni, A De Matteis, F Nuzzo, A Ardizzoni, L Crinò, T Gamucci, R Passalacqua, R Gnoni, C. Boni
Journal: Cancer Research (2010)

Abstract Background: Docetaxel (T; Taxotere) with capecitabine (X) is active against metastatic breast cancer (MBC); bevacizumab (B) has demonstrated efficacy with taxanes in the first-line setting. This study was conducted to assess the efficacy and safety of TX-B in patients (pts) with MBC. Patients and methods: In this single-arm, multicenter phase II study, pts received first-line bevacizumab 15 mg/kg and docetaxel 60 mg/m2 on day 1, plus capecitabine 900 mg/m2 twice per day on days 1-14 every 21 days. The treatment was administrated for 3 cycles and in case of objective response or stable disease at that time, pts were treated with 3 additional cycles. More courses of chemotherapy were administered at Investigator's discretion. Bevacizumab was continued until progressive disease, patient refusal, or unacceptable toxicity. Primary end point was progression-free survival (PFS) and secondary end points were tumor response rate (RR), overall survival (OS), and toxicity. Results: We report data from the first 30 pts enrolled. Median age was 54 (37-72). Eight (27%) pts had triple-negative disease, while 18 (60%) were hormone-receptor positive. HER2 status was recognized as negative in 25 (84%) pts. TX-B was administered for a median of seven cycles. Five complete and 13 partial responses were observed (overall RR 60%). Median response duration was 12 months. Median OS and PFS were 26 and 11 months, respectively. Grade 3/4 adverse events included tromboembolism (10%), neutropenia (23%), hand-foot syndrome (13%), stomatitis (10%). The median TX doses administered per cycle were 60 mg/m2 and 660 mg/m2, respectively. Ten (33%) pts required dose reductions of docetaxel, while capecitabine dose was reduced in 15 (50%) pts. Results of all the 80 assessable pts entered in the study will be presented at the meeting. Conclusion: TX-B demonstrated significant activity with an acceptable toxicity profile. Maintenance therapy with B is possible for a long period of stable tumor disease. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-17-01.
Abstract 2747: Synergistic antileukemic activity of F14512 in combination with AraC
Authors: Isabelle Vandenberghe-Huez, Arnaud Pillon, Laurent Créancier, Bruno Gomes, Jean-Philippe Annereau, Emmanuel Fournier, Viviane Brel, Valérie Cartron, Nathalie Chansard, Sandrine Pourtau, Sabine Roy, Jean-Christophe Blanchet, Jérôme Verdier, Caroline Dejean, Christel Ricome, Vanessa Offrete, Stéphane Gras, Karine André, Yves Guminski, Christian Bailly, Nicolas Guilbaud, Anna Kruczynski
Journal: Cancer Research (2012)

Abstract New antileukemic agents are urgently needed to achieve improvement of the survival of patients suffering from Acute Myelogenous Leukemia (AML). F14512 combines an epipodophyllotoxin core with a spermine moiety that targets cells with a high demand for polyamines such as cancer cells. F14512 exhibits a high level of in vivo anti-tumor activity in a series of experimental murine and human solid tumor models and has entered into clinical phase one. In this study, we investigated the in vivo antileukemic activity of F14512 against cell line or primary human AML models and evaluated its potential in combination with the reference antileukemic agent, AraC. HL60 cells or AML cells collected from different patients were engrafted onto NSG mice. Using flow cytometry and q-PCR analysis, we demonstrated that multiple administrations of F14512 for 3 weeks resulted in an extensive reduction of AML cell number in the bone marrow and blood of treated mice. We also showed in vitro and in vivo synergistic activity of F14512 in combination with AraC in HL-60 and primary AML models when both compounds were used at suboptimal doses. The mechanisms triggering primary leukemic cell death were investigated and our results indicated that senescence could be involved. Collectively, these results demonstrate that F14512 exhibits a marked in vivo antileukemic activity, supporting the Phase I clinical trials of this novel promising drug candidate. 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 2747. doi:1538-7445.AM2012-2747