tbuckley/cabot-search huggingface dataset:
Abstract 2635: association between CASP7 and CASP14 genetic polymorphisms and the risk of childhood leukemia
Authors: Chulbum Park, Nan Song, Sohee Han, Ji-Yeob Choi, Sue K Park, Sujee Jeon, Daehee Kang, Hyo Seop Ahn, Hee Young Shin, Hyoung Jin Kang, Hong Hoe Koo, Jong Jin Seo, Ji Eun Choi
Journal: Cancer Research (2012)

Abstract Current evidence suggests that apoptosis and the cell cycle system play an important role in cancer development. To identify susceptible genetic markers in these mechanisms, we did an association study in 63 patients and 148 controls. A total of 304 SNPs in 31 gene regions were selected. We evaluated an association at a gene region level by computing the minimum p-value (minP) and doing the false discovery rate (FDR) test. Both SNP and gene-based analyses presented associations with the risk of childhood leukemia for 5 genes: CASP7, CASP14, CASP8AP2, MYC, and RIPK1 (Ptrend &amp;lt; 0.05). There were statistically significant associations for CASP7 (rs12416109 and rs3814231, Ptrend = 0.002 and 0.009, respectively, minP = 0.013, FDR = 0.042) and CASP14 (rs8110862, Ptrend &amp;lt; 0.001, minP = 0.002, FDR = 0.027). This study suggests that genetic polymorphisms in apoptosis and cell cycle related genes might play a role in childhood leukemia development. 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 2635. doi:1538-7445.AM2012-2635
Spontaneous Intracerebral Hemorrhage
Authors: Adnan I. Qureshi, Stanley Tuhrim, Joseph P. Broderick, H. Hunt Batjer, Hideki Hondo, Daniel F. Hanley
Journal: New England Journal of Medicine (2001)

Nontraumatic intracerebral hemorrhage is bleeding into the parenchyma of the brain that may extend into the ventricles and, in rare cases, the subarachnoid space. Each year, approximately 37,000 to 52,400 people in the United States have an intracerebral hemorrhage.1,2 This rate is expected to double during the next 50 years as a result of the increasing age of the population and changes in racial demographics. Intracerebral hemorrhage accounts for 10 to 15 percent of all cases of stroke and is associated with the highest mortality rate, with only 38 percent of affected patients surviving the first year.3 Depending on . . .
IMPROVEMENT IN DIAGNOSIS OF CORONARY ATHEROSCLEROSIS BY RADIONUCLIDE VENTRICULOGRAPHY USING RECEIVER OPERATING CHARACTERISTIC ANALYSIS.
Authors: C. Z. Dickinson, M. B. Forman, W. K. Vaughn, M P. Sandler, M. W. Kronenberg
Journal: Clinical Nuclear Medicine (1984)

Dickinson, C. Z.; Forman, M. B.; Vaughn, W. K.; Sandler, M P.; Kronenberg, M. W. Author Information
RT-06 * GAMMA KNIFE SURGERY AFTER NAVIGATION-GUIDED ASPIRATION FOR CYSTIC METASTATIC BRAIN TUMORS
Authors: Y. Chiba, K. Mori, S. Toyota, T. Kumagai, S. Yamamoto, H. Sugano, T. Taki
Journal: Neuro-Oncology (2014)

Metastatic brain tumors over 3 cm in diameter (volume of 14.1ml) are generally considered poor candidates for Gamma Knife surgery (GKS). We retrospectively assessed the method and efficacy of GKS for large cystic metastatic brain tumors after navigation-guided aspiration under local anesthesia. From September 2007 to April 2014, 38 cystic metastatic brain tumors in 32 patients (12 males, 20 females; mean age, 63.2 years) were treated at Kansai Rosai Hospital. The patients were performed navigation-guided cyst aspiration under local anesthesia, then at the day or the next day, were performed GKS and usually discharged on the day. The methods for preventing of leptomeningeal dissemination are following: 1) puncture from the place whose cerebral thickness is 1 cm or more; 2) avoidance of Ommaya reservoir implantation; and 3) placement of absorbable gelatin sponge to the tap tract. Tumor volume, including the cystic component, decreased from 25.4 ml (range 8.7-84.7 ml) to 11.4 ml (range 2.9-36.7 ml) following aspiration; the volume reduction was approximately 51.6%. Follow-up periods in the study population ranged from 0 to 24 months (median 3.5 months). The overall median survival was 6.7 months. There was no leptomeningeal dissemination related to the aspiration. One patient experienced radiation necrosis after GKS, one patient experienced re-aspiration by failure of aspiration, and two patients experienced surgical resections and one patient experienced re-aspiration by cyst regrowth after GKS. Long-term hospitalization is not desirable for the patients with brain metastases. In japan, Long-term hospitalization is required for surgical resection or whole brain radiation therapy, but only two days hospitalization is required for GKS after navigation-guided aspiration at our hospital. This GKS after navigation-guided aspiration is more effective and less invasive than surgical resection or whole brain radiation therapy.
Gallium-67 Imaging in a Patient With Malignant Thyroid Lymphoma That Spontaneously Regressed After Subtotal Gastrectomy
Authors: Hitoya Ohta
Journal: Clinical Nuclear Medicine (2003)

A patient presented with malignant thyroid lymphoma in association with Hashimoto disease. Abnormal, intense Ga-67 accumulation in the thyroid was seen. The patient underwent subtotal gastrectomy for cancer and the malignant thyroid lymphoma regressed spontaneously. Ga-67 accumulation in the thyroid also decreased. The resected stomach was positive for Helicobacter pylori. The patient achieved complete clinical response after H. pylori eradication. Regression of the malignant thyroid lymphoma might be related to H. pylori eradication and the subtotal gastrectomy.
THU0318 General Health-Related Quality of Life Measure Shows Different Profiles in Connective Tissue Diseases Patients
Authors: E. A. Sushchuk, I. U. Kolesnikova, S. I. Krayushkin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Health-related quality of life (HRQoL) is an important domain in evaluation of health status of patients with systemic lupus erythematosus (SLE) and other connective tissue disorders (CTDs). It has been shown that HRQoL is lower in SLE and other CTDs compared to general population, but comparative data on HRQoL profiles in various CTDs in Russian patients is limited. <h3>Objectives</h3> We aimed to determine HRQoL in Russian SLE patients and to compare HRQoL profiles with other CTDs patients. <h3>Methods</h3> We used SF-36 to measure HRQoL in 129 SLE, 18 SSc, 12 PM/DM, and 25 SV patients. SF-36 scales were used to construct disease-specific HRQoL profile. ANOVA was performed to compare profiles, Spearman correlation and linear regression were used to find out determinants of SF-36 physical (PCS) and mental (MCS) component summary scores, p-values &lt;0.05 regarded significant. <h3>Results</h3> SLE patients had the following demographic and clinical features (M (SD)): age 35.67 (14.50); females 88.4%; disease duration (DD) 7.06 (6.68) years; activity scores SLAM 14.32 (6.79); SLEDAI-2K 8.76 (6.53); 91.5% received corticosteroids, 27.8% cytotoxic medications; damage by SLICC/ACR index 1.57 (1.55), 42 patients (32.6%) had no damage. SSc patients: age 48.67 (14.21); females 94.4%; DD 9.94 (10.43) years; 50% received corticosteroids. SV patients included 6 polyartereitis nodosum (24%), 12 Henoch-Shönlein vasculitis (48%), 2 Takayasu arteritis (8%), 3 Wegener's granulomatosis (12%) and 2 Churg-Strauss syndrome (8%) patients. Among PM/DM patients 9 (75%) were female, age 55.25 (12.12) years, DD 1.6 (1.91) years, all on corticosteroids. Results for profiling of HRQoL according to SF-36 scales of Physical Functioning (PF), Role-Physical Functioning (RP), Bodily pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), Mental Health (MH) are shown in the table. <h3>Conclusions</h3> HRQoL is lower in SLE and other CTDs compared to general population. HQRoL profiles are different in CTD patients. Those differences are important considerations when evaluating patients in routine practice and clinical trials. A restricted set of demographical and clinical parameters is responsible for HRQoL determinants. <h3>Disclosure of Interest</h3> None Declared
Influence of Thyroid Status on Plasma Half-Life of Antipyrine in Man
Authors: Michel Eichelbaum, Gunther Bodem, Roland Gugler, Christa Schneider-Deters, Hans J. Dengler
Journal: New England Journal of Medicine (1974)

The half-life of antipyrine in plasma was studied In four hyperthyroid and four hypothyroid patients before and after thyroid status returned to normal. The half-life (± S.E.M.) was 7.9 ± 1.0 hours In hyperthyroid and 17.3 ± 1.1 hours in hypothyroid patients. After correction of the abnormal thyroid state the half-life values of both groups (12.3 ± 0.7 and 12.0 ± 0.5 hours) were within the normal range. These results suggest that abnormalities of thyroid function can markedly influence human metabolism of some drugs. (N Engl J Med 290:1040–1042, 1974)
FRI0513 Decreased Skin Expression but Normal Circulating Levels and Function of Dickkopf-1 in Patients with Systemic Sclerosis
Authors: D. Daoussis, I. Antonopoulos, A. Tsamandas, A.P. Andonopoulos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The critical question of what drives fibroblast activation in systemic sclerosis (SSc) remains unanswered. The Wnt pathway, a known regulator of osteoblastogenesis, has also emerged as a crucial mediator of the fibrotic process. It was recently reported that Dickkopf-1 (Dkk-1), an inhibitor of the Wnt pathway, is absent from scleroderma skin<sup>1</sup>. No data exist on circulating levels and function of Dkk-1 in patients with SSc. <h3>Objectives</h3> To assess: i) circulating levels and function of Dkk-1 in patients with SSc and ii) skin expression of Dkk-1 in SSc and investigate potential correlations with clinical and demographic characteristics. <h3>Methods</h3> Circulating Dkk-1 levels were measured in 50 patients with SSc and 50 healthy subjects, age and sex matched, using an established solid phase immunoassay. The functional integrity of Dkk-1 was assessed by a functional ELISA which measures only Dkk-1 bound to LRP6 receptor. Skin biopsies were obtained from 12 patients with SSc and 5 healthy subjects and Dkk-1 skin expression was assessed by immunohistochemistry <h3>Results</h3> Patients were predominantly female (84%) with a mean age (±SEM) of 57.3 (±2.1) years. Most had diffuse disease (64%) with a mean MRSS (±SEM) of 17.1 (±1.2) and a mean (±SEM) disease duration of 8 (±1.3) years. Circulating levels of Dkk-1 did not differ significantly in patients with SSc compared to healthy subjects (mean ±SEM: 1603±154 pg/ml vs 1889±95 pg/ml for patients with SSc and healthy subjects, respectively, p=0.1). We found no correlation of circulating Dkk-1 levels with age, gender, disease duration, disease type, MRSS, HAQ-DI, inflammatory markers and PFT9s. Patients with SSc had similar functional Dkk-1 levels compared to healthy subjects (mean ± SEM: 257.8±89.5 pg/ml vs 325±74.9 pg/ml for patients with SSc and healthy subjects, respectively, p=ns). In all skin biopsies obtained from healthy subjects, Dkk-1 was expressed at the epidermis, appendices and spindle like cells in the dermis. In sharp contrast, no Dkk-1 expression could be detected in spindle-like cells in the dermis in all patients with SSc; only 2 patients exhibited a weak expression at the epidermis. <h3>Conclusions</h3> Circulating levels and function of Dkk-1 are not impaired in patients with SSc despite the striking lack of skin expression. These data indicate that local factors suppress Dkk-1 expression in scleroderma skin <h3>References</h3> Akhmetshina et al. Nat Commun 2012. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4078
Abstract 3257: Targeting small cell lung cancer harboring <i>PIK3CA</i> mutation with a selective oral PI3K inhibitor, PF-4989216.
Authors: Marlena Walls, Sangita M. Baxi, Pramod P. Mehta, Elizabeth Epps, Heather Estrella, Kevin KC Liu, JinJiang Zhu, Chunze Li, Tod Smeal, Min-Jean Yin
Journal: Cancer Research (2013)

Abstract Aberrant PI3K/AKT signaling occurs commonly in cancer. Gene mutation, amplification, and copy number gains in the catalytic p110α of PI3K have been shown in a variety of human cancers. Tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) dephosphorylates the 3-phosphoinositides and is frequently mutated, deleted, or down-regulated in many human cancers to constitutively activate the PI3K pathway. Small cell lung cancer (SCLC) patients have poor prognosis; response to second-line chemotherapy for patients with refractory disease is less than 10%, and survival is 3-4 months. Multiple phase III trials have been conducted, however the survival of SCLC patients has not significantly improved over the years. In this study, we characterized a selective PI3K inhibitor, PF-4989216, in preclinical SCLC models to investigate whether targeting the PI3K pathway may be a potential therapy for SCLC. PF-4989216 inhibits phosphorylation of PI3K downstream molecules and subsequently leads to induction in apoptosis and cell cycle block, as well as inhibition of cell proliferation, transformation, and xenograft tumor growth in SCLCs harboring a PIK3CA mutation. Moreover, our results suggest that there may be different mechanisms of tumorigenesis between PIK3CA mutation and PTEN loss in SCLCs, and indicate that PF-4989216 is a potential cancer drug candidate for small-cell lung cancer patients harboring a PIK3CA mutation. Citation Format: Marlena Walls, Sangita M. Baxi, Pramod P. Mehta, Elizabeth Epps, Heather Estrella, Kevin KC Liu, JinJiang Zhu, Chunze Li, Tod Smeal, Min-Jean Yin. Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor, PF-4989216. [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 3257. doi:10.1158/1538-7445.AM2013-3257
Fine Mapping Implicates a Deletion of CFHR1 and CFHR3 in Protection from IgA Nephropathy in Han Chinese
Authors: Jingyuan Xie, Krzysztof Kiryluk, Yifu Li, Nikol Mladkova, Li Zhu, Ping Hou, Hong Ren, Weiming Wang, Hong Zhang, Nan Chen, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2016)

An intronic variant at the complement factor H ( CFH ) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations. We investigated whether the causal sequence variant resides in the CFH gene or the neighboring complement factor H–related 1 ( CFHR1 ) gene and CFHR3 , which harbor an 84-kb combined deletion ( CFHR3,1Δ ) in linkage disequilibrium with rs6677604. Imputation of 1000 Genomes Project data did not suggest new causal single–nucleotide variants within the CFH cluster. We next performed copy number analysis across the CFH locus in two independent Han Chinese case-control cohorts (combined n =3581). The CFHR3,1Δ and rs6677604-A alleles were rare (4.4% in patients and 7.1% in controls) and in strong linkage disequilibrium with each other ( r 2 =0.95); of these alleles, CFHR3,1Δ associated more significantly with decreased risk of IgAN (odds ratio [OR], 0.56; 95% confidence interval [95% CI], 0.46 to 0.70; P =8.5 × 10 −8 versus OR, 0.61; 95% CI, 0.50 to 0.75; P =1.6 × 10 −6 for rs6677604-A). Moreover, CFHR3,1Δ explained all of the association signal at rs6677604 and remained significant after conditioning on rs6677604 genotype ( P =0.01). Exploratory analyses of clinical and histopathologic parameters using the Oxford classification criteria revealed a suggestive association of CFHR3,1Δ with reduced tubulointerstitial injury (OR, 0.46; 95% CI, 0.25 to 0.79). These data indicate that dysregulated activity of the alternative complement pathway contributes to IgAN pathogenesis in both Asians and Europeans and implicate CFHR3,1Δ as the functional allele at this locus.
NIMG-02VOLUMETRIC RELATIONSHIP BETWEEN 2-HYDROXYGLUTARATE AND FLAIR HYPERINTENSITY IN PATIENTS WITH MUTANT IDH1 GLIOMA
Authors: Kourosh Jafari-Khouzani, Franziska Loebel, Wolfgang Bogner, Elizabeth Gerstner, Andrew Chi, Tracy Batchelor, Bruce Rosen, Jan Unkelbach, Helen Shih, Daniel Cahill, Ovidiu Andronesi
Journal: Neuro-Oncology (2015)

BACKGROUND: The hallmark metabolic alteration of mutant IDH gliomas is the production of 2-hydroxyglutarate (2HG) [1], and high levels of this metabolite play a central role in downstream effects of gene mutation [2]. Hence, 2HG may be an ideal biomarker for both diagnosing IDH mutations and monitoring response to treatment. On the other hand tumor extension assessed by MRI FLAIR hyperintensity is the most used neuroimaging method for glioma treatment planning and monitoring. Here, we investigated the relationship between 2HG volume and FLAIR hyperintensity volume in a cohort of IDH mutant glioma patients. METHODS: Twenty-two patients with mutant IDH1 gliomas were imaged by MRI at 3T. A 3D MR spectroscopic imaging sequence [3] was employed to specifically image 2HG edited signal. FLAIR imaging was performed using standard clinical protocols. The overlap and displacement of 2HG and FLAIR volumes were calculated and compared. RESULTS: In 14 patients the 2HG volume was larger than the FLAIR volume. Across the entire cohort, the median volume of 2HG was 39.2 cc (95% CI = 11.7-83.1 cc) while the median volume of FLAIR was 25.7 cc (95% CI = 7.2-52.5 cc). The median displacement between the centers of mass of the 2HG and FLAIR volumes was 11.9 mm (95% CI = 6.2-22.2 mm). CONCLUSIONS: Our results indicate that for most patients the 2HG volumetric assessment of tumor burden is more extensive than the FLAIR volume. In addition, there is frequently an asymmetric displacement between the center of tumor volume probed by FLAIR and the center of 2HG volume. These results may have important implications for treatment planning and monitoring.
Abstract 31: Activated phosphatidylinositol-3 kinase: An oncogene that increases gap junctional, intercellular communication
Authors: Mulu Geletu, Samantha Greer, Leda Raptis
Journal: Cancer Research (2012)

Abstract Gap junctions are channels that connect the cytoplasm of adjacent cells. Gap junctional, intercellular communication (GJIC) is blocked in cells transformed by oncogenes such as the middle Tumor antigen of polyoma virus (mT), an oncoprotein which associates with and is tyrosine-phosphorylated by cSrc family members. Specific phosphotyrosines provide docking sites for the phosphotyrosine binding domain of Shc (mT-tyr250) and the SH2 domain of the phosphatidylinositol 3-kinase (mT-tyr315), resulting in the activation of their downstream signaling cascades, Ras/Raf/Erk and PI-3 kinase/Akt, respectively. To examine the effect of these mT-initiated pathways upon gap junctional communication and neoplasia, GJIC was assessed in mT-mutant-expressing, rat liver epithelial T51B cells which normally have extensive GJIC, using a novel technique of in situ electroporation we developed. The results show that although low levels of wt-mT are sufficient to interrupt gap junctional communication, GJIC suppression still requires an intact tyr250 site, that is activation of the Ras pathway. In sharp contrast, activation of the PI-3 kinase pathway is not required for GJIC suppression. It is remarkable that T51B cells expressing a mutant deficient in binding of Shc, hence activation of the Ras pathway, are still morphologically transformed and do grow into tumors in syngeneic rats, albeit with an altered morphology. These results indicate that GJIC suppression requires Ras but not PI-3 kinase/Akt signalling, and is independent of full neoplastic conversion in rat liver epithelial cells. Since PI3k activation by mT increases GJIC, we examined whether PI3k might have a positive role upon GJIC. The results showed that PI3k pharmacological inhibition eliminates GJIC, concomitant with apoptosis induction. We next expressed a form of PI3k rendered constitutively active through the addition of a myristylation signal (myr-PI3k). The results demonstrated that myr-PI3k causes an increase in GJIC. Therefore PI3k, although in an activated form it can act as an oncogene, it plays a positive role upon gap junctional, intercellular communication. 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 31. doi:1538-7445.AM2012-31
RISK OF STROKE OR TRANSIENT ISCHEMIC ATTACKS WITH PERIPROCEDURAL DABIGATRAN IN PATIENTS UNDERGOING CATHETER ABLATION FOR ATRIAL FIBRILLATION: EVIDENCE FROM A META-ANALYSIS OF OBSERVATIONAL STUDIES
Authors: Partha Sardar, Saurav Chatterjee, Ramez Nairooz, Joydeep Ghosh, Wetterslev Jrn, Wilbert Aronow
Journal: Journal of the American College of Cardiology (2014)
PWE-021 Secondary care costs in oesophagogastric cancer in the UK: a single centre micro-costing study
Authors: N Stern, A Bassi, K Bodger
Journal: Gut (2012)

<h3>Introduction</h3> Published data describing the scale, profile and determinants of healthcare resource use for oesophago-gastric cancer (OGC) are scarce, particularly for the UK. The National Cancer Plan (2000) encouraged greater use of imaging for staging and increased use of oncological therapies but the major modalities of palliation and curative surgery have changed little over the last decade. We have reported how emergency presentation predicts a poor outcome<sup>1</sup> and now aimed to study the effect of this mode of presentation on resource use and cost. <h3>Methods</h3> Using cohorts of all patients presenting with OGC to a single university hospital trust (Aintree University Hospital, Liverpool, UK) over two, 2-year periods (July 1997–June 1999 and Jan 2001–Dec 2002) we audited all resource use from referral to diagnosis and 12 months post-diagnosis or death (whichever was sooner). Diagnostic and staging investigations, in-patient bed days and treatments including surgical, oncological and endoscopic were all itemised. Patient treatment was categorised according to initial intent. Individual hospital based unit costs or HRG tariffs (2010/2011 financial year) were applied to derive per-patient costs for the cohorts. <h3>Results</h3> Of 333 patients identified, 320 had complete data to enable cost analysis. Median cost per-patient was £11 965.94 with annualised costs to our institution of £1.2 million. Potentially curative treatment accounted for 32.5% of institutional costs, palliation 56.2% and supportive care 11.3%. Per-patient costs [median (IQR)]: Curative treatment: £11 863.80 (9701–17 430); Palliative treatments: £14 288.52 (10 016–22 710); Supportive care only: £6619.96 (3567–11 778). Emergency presentations (31.2% of cases) consumed 30.8% of cost despite shorter survival with significant increased costs per live day (£148.14 vs 71.61, p&lt;0.001), mostly due to longer inpatient stays. Linear regression of log transformed costs confirms that emergency presentation increased cost per live day independently of age or potentially curative treatment. Endoscopic interventions were used in 33.4% patients. <h3>Conclusion</h3> Managing OGC has a significant impact on healthcare resources with most expenditure is for those treated with palliative intent. Presenting as an emergency increases costs per live-day compared to elective presentation. These primary data can support modelling studies of cost-effectiveness of rival programmes or treatments for OGC. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Shawihdi M</b>, Stern N, Thompson E, <i>et al.</i> Emergency admission as a route for oesophago-gastric cancer diagnosis: a marker of poor outcome and a candidate quality indicator for local services. <i>Gut</i> 2011;<b>60</b>(Suppl 1):A30–1.