tbuckley/cabot-search huggingface dataset:
Abstract 1874: The role of functional polymorphisms in folate metabolism on 6-mercaptopurine-mediated hematological toxicity in children with acute lymphoblastic leukemia
Authors: Dorababu Patchva, Vijay Gandhi Linga, Raghunadharao Digumarti
Journal: Cancer Research (2012)

Abstract Purpose: Defective S-methylation of 6-mercarptopurine (6-MP) either due to reduced activity of thiopurine s-methyltransferase (TPMT) or due to reduced synthesis of S-adenosyl methionine (SAM) induces hematological toxicity in children undergoing 6-MP treatment for acute lymphoblastic leukemia (ALL). Recently, we have demonstrated the genetic variants of TMPT results in hematological toxicity when on 6-MP. In the current study, we have aimed to explore the role of seven functional polymorphisms in folate metabolism as pharmacogenomic determinants of 6-MP mediated toxicity. Experimental Procedures: In 126 children with ALL being treated with 6-MP, Glutamate carboxypeptidase II (GCPII) C1561T, Reduced folate carrier 1 (RFC1) G80A, cytosolic serine hydroxymethyl transferase (cSHMT) C1420T, Thymidylate synthase (TYMS) 3′-UTR ins6/del6, Methylene tetrahydrofolate reductase (MTHFR) C677T, Methionine synthase (MTR) A2756G polymorphisms were analysed by PCR-RFLP method while TYMS 5′-UTR 28 bp tandem repeat analysis was done by PCR-AFLP method. Summary: Univariate analysis showed positive association of GCPII C1561T (r= 0.23) and cSHMT C1420T (r=0.15) variants with hematological toxicity. Multi dimensionality reduction analysis confirmed synergetic gene-gene interaction between these two loci (×2=5.9, p=0.02) apart from showing an interesting tri-variate interaction i.e, RFC1 G80A/cSHMT C1420T/TYMS 5′-2R3R. RFC1 G80A showed additive interaction with cSHMT while TYMS 2R alleles showed counteracting interaction. Toxicity grade prediction model was developed using multiple linear regression approach, which showed moderate predictability of aberrations in folate metabolism and TPMT*3C (Area under the receiver operating characteristic curve=0.69) thus explaining 36% variation in toxicity. Conclusion: Aberrations in folate metabolism and TPMT*3C contribute to 36% 6-MP mediated toxicity. 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 1874. doi:1538-7445.AM2012-1874
Tc-99m HMPAO Uptake in Renal Cell Carcinoma Metastases
Authors: E Tsukamoto, A Takamura, Y Sakurai, H Saito, N Tamaki
Journal: Clinical Nuclear Medicine (1997)

A 77-year-old man with renal cell carcinoma underwent Tc-99m HMPAO scintigraphy to evaluate a brain mass seen on CT scan after radiation therapy. Tc-99m HMPAO SPECT imaging showed intense accumulation in the nasal cavity and in the parietal bone. These lesions were well seen on CT with contrast enhancement and were thought to be suggestive of hypervascularity. They were in fact hypervascular. The tumor in the nasal cavity had been histologically proven to be a metastasis from a renal cell carcinoma.
Distribution of Salmonella enterica isolates from human cases in Italy, 1980 to 2011
Authors: C Graziani, L Mughini-Gras, S Owczarek, A M Dionisi, I Luzzi, L Busani
Journal: Eurosurveillance (2013)

We describe trends of Salmonella enterica serovars isolated from humans in Italy from January 1980 to December 2011. A total of 229,279 Salmonella isolates were reported during this period. Serovars Enteritidis, Typhimurium, Infantis, Derby, 4,[5],12,:i:-, and Napoli accounted for 135,783 (59%) of these isolates. Temporal trends from 2000 to 2011 varied by serovar: Enteritidis and Infantis decreased significantly (with a mean of -3.0% and -2.8% isolates per year, respectively, p&lt;0.001); Typhimurium remained stable; while 4,[5],12:i:-, Derby and Napoli increased significantly (+66.4%, p&lt;0.001; +8.1%, p&lt;0.001; and +28.2%, p&lt;0.05, respectively). Since 2000, Enteritidis fell consistently below Typhimurium, which is the most reported serovar in Italy in contrast to the international situation where Enteritidis still ranks at the top despite its significant decrease. Most serovars showed a marked seasonality, increasing over the summer months and peaking in August/September. Typhimurium, 4,[5],12:i:-, and Napoli were most likely to be isolated from children, whereas Enteritidis, Derby, and Infantis from adults. We conclude that the applied control measures are not equally efficient against the considered Salmonella serovars and that sources of infection other than those of Enteritidis (laying hens and eggs) have become increasingly important. Further investigations on the emerging serovars and on the causes related to their emergence are needed to define and implement newly tailored control measures.
PROLONGED QRS, MECHANICAL DYSSYNCHRONY AND VENTRICULAR DILATION ARE ASSOCIATED WITH VENTRICULAR ARRHYTHMIAS LATE AFTER THE FONTAN OPERATION
Authors: Sunil J. Ghelani, Ellen M. Keenan, Douglas Mah, David Harrild, Andrew Powell, Tal Geva, Rahul Rathod
Journal: Journal of the American College of Cardiology (2016)
Abstract 910: Isothiocyanate-gene interactions and endometrial cancer risk: the California Teachers Study
Authors: Pamela L. Horn-Ross, Alison J. Canchola, Leslie Bernstein, David Van Den Berg, Giske Ursin
Journal: Cancer Research (2010)

Abstract Background: Cruciferous vegetables may reduce the risk of endometrial cancer, although the evidence is mixed. However, as observed for other cancers, this association may be modified by polymorphic variation in phase I genes (e.g., CYP1A1 which also controls estrogen metabolism) and phase II genes (e.g., GSTs). Such interactions have not been previously examined for endometrial cancer. Methods: A nested case-control study of type 1 invasive endometrial cancer was conducted within the California Teachers Study (CTS) cohort. 320 women (age≥50) with incident cancer, identified through the California Cancer Registry and diagnosed after joining the cohort and before January 2005, and 629 controls, frequency-matched on age, race/ethnicity, and broad geographic region of residence within California, provided a DNA sample and had complete epidemiologic data. Consumption of cruciferous vegetables was assessed using a validated food-frequency questionnaire at the time women joined the cohort in 1995-96. Isothiocyanate (ITC) consumption was estimated using values obtained from prior analysis of California foods and was based on frequency and portion size of usual consumption of cruciferous vegetables. Selected single nucleotide polymorphisms (SNP) in several phase I and II genes were genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for matching variables. Results: Neither cruciferous vegetable or ITC intake, nor variants in CYP1A1 MspI (rs4646903), GSTM1, or GSTT1 were directly associated with endometrial cancer risk. The Val/Val genotype of GSTP1 Ile105Val was associated with increased endometrial cancer risk (OR=1.64, 95% CI: 1.07-2.53) and the Val/Val genotype of CYP1A1 Ile462Val was associated with reduced risk (OR=0.63, 95% CI: 0.37-1.08). There was no interaction, however, between cruciferous vegetable or ITC intake and any of these genes. Conclusion: Consistent with some, but not all, previous studies we observed a significant reduction in risk associated with the Val/Val genotype of CYP1A1 Ile462Val. This study also confirms a single previous, but smaller report of an association between type I endometrial cancer and the Ile105Val SNP in GSTP1. However, while the prospective assessment of dietary intake minimizes recall bias, we found no evidence of an interaction between these genetic variants and ITC consumption. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 910.
11C-Choline PET/CT and Bladder Cancer
Authors: Francesco Ceci, Lorenzo Bianchi, Tiziano Graziani, Paolo Castellucci, Christian Pultrone, Brunocilla Eugenio, Giuseppe Martorana, Patrick M. Colletti, Domenico Rubello, Stefano Fanti, Riccardo Schiavina
Journal: Clinical Nuclear Medicine (2014)

The aim of this study was to evaluate the potential role of C-choline-PET/CT in nodal assessment in patients with bladder cancer (BCa) using the pathological specimen as reference standard.Fifty-nine patients with proven BCa were retrospectively enrolled from April 2011 to January 2014 (mean [SD] age, 70.1 [9] years; range 49-85 years). Of 59 patients, 39 (staging group) were referred to C-choline-PET/CT for preoperative lymph node (LN) evaluation before radical cystectomy and extended pelvic LN dissection. Of the 59 patients, 29 (restaging group) had C-choline-PET/CT for suspected BCa relapse after primary radical surgery. In both groups, C-choline-PET/CT findings were correlated with histology. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to assess C-choline-PET/CT feasibility in LN assessment. Age, TNM, histology, and previous chemotherapy were analyzed as additional predictive factors.C-choline-PET/CT overall detection rate was 62.7% (37/59 patients). On a regional-based analysis, C-choline-PET/CT was considered positive for primary cancer and/or local relapse in bladder bed in 54.2% of the patients (32/59). Pathological LN uptake was reported in 23.7% of the patients (14/59) and systemic choline deposit (bone or lung) in 11.8% of the patients (7/59). Considering LN metastasis detection, compared with histological analysis, C-choline-PET/CT showed in the whole population a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 59%, 90%, 71%, 84%, and 81%, respectively. No other investigated factors reached statistical significance.C-choline-PET/CT may provide additional diagnostic information in preoperative nodal staging of patients with BCa and be considered a useful tool to restage patients with BCa suspected of relapse. Further studies are needed to assess if C-choline-PET/CT could have an influence on survival of patients with BCa.
Abstract 1622: Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis.
Authors: Zhi-Yuan Chen, Ming Shi, Li-Xia Peng, Wei Wei, Xin-Jian Li, Zhi-Xing Guo, Shu-Hong Li, Chong Zhong, Chao-Nan Qian, Rong-Ping Guo
Journal: Cancer Research (2013)

Abstract Background: Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC), however, its cellular target is not clarified. Method: In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib. Results: Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-β was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.05 μmol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells. Conclusion: Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells. Citation Format: Zhi-Yuan Chen, Ming Shi, Li-Xia Peng, Wei Wei, Xin-Jian Li, Zhi-Xing Guo, Shu-Hong Li, Chong Zhong, Chao-Nan Qian, Rong-Ping Guo. Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis. [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 1622. doi:10.1158/1538-7445.AM2013-1622
Abstract B13: Implication of RNA-binding protein La in proliferation, migration, and invasion of oropharyngeal squamous cell carcinoma cells
Authors: Gunhild Sommer, Carlos Rossa, Angela C. Chi, Brad W. Neville, Tilman Heise
Journal: Cancer Research (2011)

Abstract The 5-year survival rate for oral cavity cancer is poorer than for breast, colon, or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here, we demonstrate by tissue microarray (TMA) analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). We therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration, and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of β-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together, these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B13.
OC-033 The Tweak And Fn14 Pathway As Potential Mediator Of Liver Fibrosis
Authors: A Wilhelm, M Munir, E Humphreys, D Adams, L Burkly, S Afford, C Weston
Journal: Gut (2014)

Introduction The TNF superfamily ligand TWEAK and its cognate receptor Fn14 have been implicated in the pathogenesis of liver disease and have been predominantly associated with liver progenitor cell proliferation and ductular reaction. We hypothesised that TWEAK and Fn14 may also be involved in the establishment and progression of fibrosis via a direct effect on hepatic stellate cell (HSC) function. Methods TWEAK and Fn14 expression was studied by qPCR, western blot and immunostaining in tissue and stromal cells from explanted human liver specimens and normal donor livers surplus to surgical requirements, or as a byproduct of surgical resection. The responses of HSCs to TWEAK were investigated by western blot, live cell imaging and proliferation assays. TWEAK was measured in HSC supernatant by ELISA. Results Confocal microscopy revealed localisation of Fn14 to cells expressing stromal markers in normal human livers, with significant upregulation in diseased livers. Fn14 expression was confirmed in both primary human HSCs and myofibroblasts in vitro . Stimulation with recombinant TWEAK led to an upregulation of NF-kB signalling and induced proliferation in cultured HSCs. TWEAK immunostaining localised the protein to the fibrotic areas of ALD and NASH liver sections suggestive of an autocrine regulation of Fn14 signalling. We confirmed that HSCs express TWEAK and release it into their environment by qPCR and ELISA, and demonstrated that function-blocking TWEAK antibodies reduced the proliferative capacity of HSC. Conclusion Our study suggests that TWEAK/Fn14 promotes liver fibrosis via enhanced proliferation of HSC, possibly through an autocrine mechanism driven by HSC production of TWEAK. Disclosure of Interest None Declared.
Abstract 1808: Modulation of the immune cell repertoire and immunogenicity of tumor cells by sorafenib
Authors: Barbara Seliger, Corinna Giersberg, Anja Mueller
Journal: Cancer Research (2010)

Abstract Recently, tyrosine kinase inhibitors have been successfully implemented in frontline therapy for the treatment of malignant tumors including renal cell carcinoma (RCC). These different substances provide significant objective clinical responses and a longer progression-free survival of patients. This is mainly caused by the inhibition of cell growth, angiogenesis and induction of apoptosis. In addition, an effect of sorafenib on the frequency and function of T subpopulations, dendritic cells as well as myeloid-suppressor cells has been postulated. The aim of this study was to determine the effect of sorafenib on cell growth, apoptosis and immunogenic properties of RCC cells as well as on the composition of immune subpopulations of peripheral blood mononuclear cells and subsequently immune responses. A direct effect of sorafenib on the expression pattern of a number of immune modulatory components including HLA class I antigens and members of the B7-H family as well as on the proliferation of RCC cell lines was detected. In addition, the frequency and function of different immune cell populations, such as regulatory T cells and myeloid-derived suppressor cells, was altered upon sorafenib treatment. These data suggest a novel activity of sorafenib in tumor patients by extending its activity beyond the tumor endothelium as its major target to the modulation of immune cell function and the immunogenicity of RCC cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1808.
Abstract 4343: X-ray detection of hepatocellular carcinoma (HCC) using gold nanoparticles conjugated to HCC-specific SF25 antibodies
Authors: Vivian Ortiz, Zoltan Derdak, Yanan Liu, Gerald Diebold, Jack R. Wands, Christoph Rose-Petruck
Journal: Cancer Research (2010)

Abstract There is widespread concern among health care professionals regarding the increase in HCC and the lack of optimal detection methods that lead to early diagnosis and treatment. It is hoped that early diagnosis may improve the prognosis of this almost uniformly fatal disease. There are substantial issues with false/negatives and false/positives and better, more specific and sensitive detection methods are urgently needed. For this reason, we aimed to design a novel detection method that is based on phase-sensitive x-ray imaging of gold nanoparticles, conjugated with HCC specific antibodies. Our laboratory has previously established various liver cancer specific antibodies by screening antigens that were uniquely present in the FOCUS hepatocellular carcinoma cell line. In the current study we used the SF25 antibody that is known to cross-react with a 125 kDa cell surface antigen. 10 nm gold nanoparticles were coated with polyacrylic acid (PAA) and poly(allylamine hydrochloride) (PAH), followed by conjugation with the SF25 antibody. The specificity of our antibody was confirmed in vitro by Western-blotting and immunoflurescence using FOCUS and NIH/3T3 cells (negative control). The gold labeling did not interfere with the immunofluorescent detection of SF25 antigen. The cellular localization of the SF25 protein was further confirmed by transmission electron microscopy. A labeling density of 10^4 gold particles per HCC cell was achieved. Given the sensitivity of the phase contrast imaging modality, this labeling density was also sufficient to enhance noticeably the density of subcutaneously raised HCC xenografts in vivo relative to healthy tissue. 10^7 cells were injected in the flanks of athymic nude mice. 1 week after inoculation the tumors were in vivo labeled by gold nanoparticle-conjugated SF25 antibodies. The gold content of these tumors were further quantified by x-ray fluorescence (XRF), which revealed gold fluorescence lines in the x-ray spectrum. These findings suggest that this imaging technique holds high in vivo potential for early detection of HCC. We envision that besides tumor detection, our x-ray imaging modality using nanoparticle-immunolabels will be useful for observing the delivery of drugs attached to or enclosed in nanoparticles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4343.
Perfusion Nephropathy in Human Transplants
Authors: David Spector, Catherine Limas, James L. Frost, James B. Zachary, Sylvester Sterioff, G. Melville Williams, Ronald T. Rolley, John H. Sadler
Journal: New England Journal of Medicine (1976)

To determine whether perfusion preservation affected the structure and survival of kidney transplants, we correlated clinical and histologic data in 77 kidneys biopsied one hour after transplantation. Twenty-one of 36 perfusion-preserved kidneys had a glomerular capillary lesion suggestive of intravascular coagulation. None of 41 kidneys preserved by hypothermia alone had this lesion. Presence of the lesion did not correlate with donor or recipient characteristics, warm or cold ischemia time, HLA match, percentage of preformed lymphocytotoxic antibody titers or perfusion characteristics. Of 21 transplants with the lesion, nine required nephrectomy by one month, and one-month serum creatinine was less than 2.0 mg per deciliter in only three of the remaining 12 transplants. We conclude that perfusion preservation may cause pathologic changes that may adversely affect kidney-transplant function. The causes of the pathologic process remain unclear.
Abstract 1410: Forced expression of EWS/ATF1 induces sarcomas in mice.
Authors: Kazunari Yamada, Takatoshi Ohno, Akira Hara, Yasuhiro Yamada, Katsuji Shimizu
Journal: Cancer Research (2013)

Abstract Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs. In addition, the cells of origin for CCSs remain to be determined. We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult somatic cells. We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as S100, Sox10, and Mitf. Lineage tracing experiments using Wnt1-Cre and P0-Cre alleles indicated that neural crest-lineage cells are permissive to EWS-ATF1-driven transformation. Citation Format: Kazunari Yamada, Takatoshi Ohno, Akira Hara, Yasuhiro Yamada, Katsuji Shimizu. Forced expression of EWS/ATF1 induces sarcomas in mice. [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 1410. doi:10.1158/1538-7445.AM2013-1410