tbuckley/cabot-search huggingface dataset:
Abstract 2580: A mosaic ERG oncoprotein staining pattern predicts upstaging and poor pathologic features in prostate cancer patients
Authors: William Gesztes, Shahnoza Dusmatova, Justin Mygatt, Jennifer Cullen, Denise Yong, Huai-Ching Kuo, Yongmei Chen, Lauren Hurwitz, Inger Rosner, Shiv Srivastava, Isabell Sesterhenn
Journal: Cancer Research (2018)

Abstract Purpose: Building on previous work, this study examined the independent role of ERG staining pattern in the index prostate cancer (CaP) tumor, on probability of upstaging and biochemical recurrence (BCR) following radical prostatectomy (RP). Methods: A retrospective cohort study of patients enrolled at the Walter Reed National Military Medical Center who underwent RP between 1993 and 2016 was conducted. ERG oncoprotein expression was assessed in CaP index tumors (i.e., largest and poorest grade) using immunohistochemistry (IHC) staining with 9FY monoclonal antibody of representative sections of formalin-fixed paraffin-embedded whole-mounted RP specimens. ERG status was classified as positive (ERG+), negative (ERG-) and a pattern of alternating +/- regions within the index tumor (ERG “Hybrid” or ERG-h). Kaplan Meier (KM) estimation curve analysis was used to examine BCR-free survival across ERG status. Multivariable (MV) logistic regression (LR) modeling was used to determine whether ERG status predicted upstaging (cT1-2 to pT3-4). Results: Among 1,385 eligible patients, mean age at RP and follow up time were 58.8 and 7 years, respectively. Twenty-nine percent of patients self-classified as African-American (AA), and 18% experienced BCR. The ERG-h pattern was observed in 81 patients (5.8%). Pathologic stage T3a-T4a was observed in 51.3%, 32.2% and 30.5% of patients with ERG-h, ERG+ and ERG- tumors, respectively. In unadjusted KM analysis, 10-year BCR-free survival probabilities were 78%, 75%, and 82% for ERG-h, ERG-, and ERG+ patients, respectively (p=0.08). A trend of incrementally poorer BCR-free survival was observed for ERG-h, ERG- versus ERG positive patients. MV LR analysis revealed the greatest odds of upstaging for ERG-h vs. ERG- patients (OR=2.8, p=0.0008), controlling for age at RP (p&amp;lt;.0001), biopsy Gleason score (p&amp;lt;.0001), PSA at diagnosis (p=0.0054) and patient race (p=0.07). Conclusions: In this racially diverse cohort of RP patients, a mosaic-like pattern of ERG staining predicted greater upstaging and poorer pathologic features. There may be a role for examination of this “hybrid” mosaic staining pattern in patient risk stratification during treatment decision making. Citation Format: William Gesztes, Shahnoza Dusmatova, Justin Mygatt, Jennifer Cullen, Denise Yong, Huai-Ching Kuo, Yongmei Chen, Lauren Hurwitz, Inger Rosner, Shiv Srivastava, Isabell Sesterhenn. A mosaic ERG oncoprotein staining pattern predicts upstaging and poor pathologic features in prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2580.
Free-Floating Thrombi in the Right Heart
Authors: LudovicChartier, JérômeBéra, MaxenceDelomez, PhilippeAsseman, Jean-PaulBeregi, Jean-JacquesBauchart, HenriWarembourg, ClaudeThéry
Journal: Circulation (1999)

Background—Floating right heart thrombi (FRHTS) are a rare phenomenon, encountered almost exclusively in patients with suspected or proven pulmonary embolism and diagnosed by transthoracic echocardiography. Their management remains controversial. Methods and Results—We report on a series of 38 consecutive patients encountered over the past 12 years. Thirty-two patients were in NYHA class IV, 20 in cardiogenic shock. Echocardiography usually demonstrated signs of cor pulmonale: right ventricular overload (91.7% of the population), paradoxical interventricular septal motion (75%), and pulmonary hypertension (86.1%). The thrombus was typically wormlike (36 of 38 patients). It extended from the left atrium through a patent foramen ovale in 4 patients. Pulmonary embolism was confirmed in all but 1. Mortality was high (17 of 38 patients) irrespective of the therapeutic option chosen: surgery (8 of 17), thrombolytics (2 of 9), heparin (5 of 8), or interventional percutaneous techniques (2 of 4). The in-hospital ...
Abstract 659: A novel manganese MRI contrast agent (PyC3A) for the evaluation of hepatic neoplasms
Authors: Derek J. Erstad, Ian Ramsay, Mozhdeh Sojoodi, Christian Farrar, NIcholas J. Rotile, Shen Li, Sarani Ghoshal, Lanuti Michael, Peter Caravan, Kenneth K. Tanabe, Bryan C. Fuchs, Eric Gale
Journal: Cancer Research (2018)

Abstract Introduction: Magnetic resonance imaging (MRI) is routinely used to diagnosis hepatic neoplasms. However, Gadolinium (Gd) is contraindicated in patients with severe renal impairment, and recent evidence also suggests Gd accumulates in brain tissue after repeated contrast injections. Manganese (Mn2+) is a paramagnetic ion that is cleared via biliary excretion, and provides an ideal alternative to Gd-based MR contrast agents. We present a novel Mn-based contrast agent, [Mn(PyC3A)(H2O)]- (referred to as PyC3A), and compare its efficacy to gadoxetic acid (Eovist) by imaging orthotopically implanted colorectal cancer hepatic metastases in mice. Methods: Male BALB/c mice (n = 8) were injected in the left lobe of the liver with 5x104 MC26/MCA-26 murine colon carcinoma cells, and were imaged on postoperative day 10 using a 4.7T MR scanner with PyC3A and gadoxetic acid (Eovist) 24 hrs apart. Signal contrast-to-noise ratio (CNR) was calculated for normal liver relative to tumor for each probe and compared. Results: Relaxivity of PyC3A in blood plasma was shown to be comparable to commercial Gd contrast agents. Biodistribution analysis confirmed that PyC3A clears via a mixed renal/hepatobiliary pathway with greater than 99% clearance within 24 hours. For imaging hepatic metastases, all mice survived to the study endpoint and developed radiographically discernible tumors (5 ± 2 mm diameter) without evidence of carcinomatosis. Calculated CNRs for liver relative to tumor for all recorded times are shown in Table 1. There was no difference in CNR between gadoxetic acid and PyC3A for all time points, suggesting near-equivalent enhancement of normal liver and tumor by both probes. Conclusions: PyC3A provides resolution of metastatic liver metastases that is comparable to gadoxetic acid. PyC3A may provide a safe and effective alternative to Gd constrast agents for imaging hepatic neoplasms in patients with renal impairment. Table 1. Contrast-to-Noise Ratio (CNR) of Normal Liver Relative to TumorTime (minutes post injection)Gadoxetic AcidPyC3Ap-value02.61 ± 1.082.60 ± 1.640.9237.72 ± 4.677.53 ± 3.020.9387.85 ± 3.898.85 ± 4.430.66138.02 ± 3.987.62 ± 5.490.88189.79 ± 4.175.60 ± 3.080.06238.72 ± 4.167.03 ± 2.060.36 Citation Format: Derek J. Erstad, Ian Ramsay, Mozhdeh Sojoodi, Christian Farrar, NIcholas J. Rotile, Shen Li, Sarani Ghoshal, Lanuti Michael, Peter Caravan, Kenneth K. Tanabe, Bryan C. Fuchs, Eric Gale. A novel manganese MRI contrast agent (PyC3A) for the evaluation of hepatic neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 659.
Abstract 581: Feasibility test of KRAS mutation in urine circulating tumor DNA in metastatic pancreatic ductal adenocarcinoma
Authors: Min Jeong Kwon, Min Kyeong Kim, Sang Myung Woo, Kyong-Ah Yoon, Yun Hee Kim, Boram Park, Jung Nam Joo, Sang Jae Park, Sun-Young Kong
Journal: Cancer Research (2018)

Abstract Circulating tumor DNA (ctDNA) has been known to be released from tumor cells and evaluated as potential biomarkers for therapeutic responses. In our previous study, we selected KRAS mutation and evaluated applicability as a prognostic marker through the quantitative analysis of plasma ctDNA. Then we proved that KRAS mutation of ctDNA from plasma is significant biomarker for prediction of clinical outcome in pancreatic ductal adenocarcinoma (PDA). Here we investigated whether KRAS mutation in urine ctDNA had the prognostic impact as shown of plasma ctDNA. Of the 106 patients enrolled, 67 were males and median age was 66 years. Total of 51 PDA has been enrolled in this study and the median age was 63 years old and 30 males (58.8%). Urine was separated by established centrifugation method and ctDNA were extracted using QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) from 4 mL of urine. Extracted ctDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). QX200 Droplet Digital PCR System (Biorad, USA) was applied to measure frequency of KRAS mutation by KRAS screening multiplex droplet digital PCR kit, which covers seven common mutation sites (Biorad, USA). Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). There was no significant difference between resectable (N=21), locally advanced (N=11) and metastatic (N=19) groups. When compared high versus low KRAS mutation concentration and KRAS fractional abundance group in each stage, high KRAS mutation groups showed short overall survival (p = 0.0321) in metastatic group. However, the correlation between plasma and urine was low (r=0.193) in metastatic group. This study represented the possibility of KRAS mutation concentration and fractional concentration of urine ctDNA as prognostic factors in metastatic PDA. Urine cfDNA role has not been well investigated in PDA. Urine is easy to obtain and is not well known for its mechanism. Therefore, we have conducted a pilot study and we will explore KRAS mutation status in urine ctDNA in further studies. (This study was supported by National Cancer Center, Korea, Grant no. 1510203.) Citation Format: Min Jeong Kwon, Min Kyeong Kim, Sang Myung Woo, Kyong-Ah Yoon, Yun Hee Kim, Boram Park, Jung Nam Joo, Sang Jae Park, Sun-Young Kong. Feasibility test of KRAS mutation in urine circulating tumor DNA in metastatic pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 581.
Abstract A10: Epigenetic mechanisms in liver tumors: Gene expression analysis of epigenetic machinery in hepatoblastomas
Authors: Maria Rivas, Cecília da Costa, Silvia Toledo, Monica Cypriano, Luiz Caires, Ernesto Goulart, Dirce Carraro, Isabela Werneck, Carla Rosenberg, Mayana Zatz, Ana Krepischi
Journal: Clinical Cancer Research (2018)

Abstract Liver tumors in children are rare and account for only 1-4% of all pediatric solid tumors. While hepatocellular carcinoma is predominant in adults, the most common liver cancer in children is hepatoblastoma, an embryonal tumor. The prognosis of patients with advanced tumor stages remains poor as well as surviving children often face severe effects following aggressive chemotherapy. Hepatoblastomas carry a low mutational burden, and the impairment of epigenetic mechanisms, which are the core of embryogenesis and development, stands out as an alternative route for tumorigenesis. The main objective of this study was to explore the role of genes associated with methylation and hydroxymethylation in hepatoblastomas. The expression of seven genes of the epigenetic machinery (DNMT1, DNMT3A, DNMT3L, UHRF1, TET1, TET2, and TET3) was analyzed by qPCR (Taqman). The cohort of tumors consisted of 21 hepatoblastomas and a control group of 8 non-tumor differentiated liver tissues. Additionally, a 5hmC quantification assay (Quest 5-hmC DNA ELISA Kit) was applied to assess the level of 5hmC in tumors. TET1 and TET2 genes, whose proteins are responsible for the active demethylation of 5-methylcytosine (5mC), and consequent production of 5-hydroxymethylcytosine (5hmC), were found to be upregulated. A significant increase in the 5hmC levels was also evident in tumor samples when compared to nontumoral tissues. We have shown in hepatoblastomas an upregulated profile of TET1 and TET2 enzymes with a resulting elevation of 5hmC level in tumors. Our data suggest that hepatoblastomas could present a pluripotency pattern of gene expression when compared to differentiated livers; to address this issue, the expression levels of three genes associated with pluripotency (POU5F1, SOX2 and NANOG) were evaluated, with no significant alteration. Therefore, although hepatoblastomas have a more undifferentiated molecular profile than mature hepatocytes, our results indicate that tumor cells are already commited with the differentiation process. Altogether, these data suggest that the development of hepatoblastomas is associated with a blockage in the stages of hepatoblasts. Citation Format: Maria Rivas, Cecília da Costa, Silvia Toledo, Monica Cypriano, Luiz Caires, Ernesto Goulart, Dirce Carraro, Isabela Werneck, Carla Rosenberg, Mayana Zatz, Ana Krepischi. Epigenetic mechanisms in liver tumors: Gene expression analysis of epigenetic machinery in hepatoblastomas [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A10.
Abstract 3560: Targeting the MIF receptor CD74 in bladder cancer tumorigenesis
Authors: Justin Penticuff, Sambantham Shanmugam, Joshua Warrick, Brian Chase, Erika Abbott, Benjamin L. Woolbright, John A. Taylor
Journal: Cancer Research (2018)

Abstract Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that can stimulate cellular proliferation in multiple tumors. Our previous data indicates genetic deletion of MIF results in T1 stage arrest in the N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced bladder cancer model. Similarly, pharmacological inhibition of MIF results in lower stage tumors and reduced bladder weights when given therapeutically. CD74 is a human leukocyte antigen class II trafficking and processing protein that also functions as an extracellular receptor for MIF. Additionally, CD74 complexes with CD44 to act as the cognate MIF receptor complex, and upregulation of CD74 has been noted in high grade bladder cancer. We hypothesized CD74 would be upregulated in malignant bladder cancer cell lines, and knockout of CD74 would reduce bladder cancer tumorigenesis in the murine BBN model. The objectives of this study were to determine the effect of CD74 knockout on development and progression of urothelial cell carcinoma; as well as evaluate expression of the putative MIF signaling axis in BCa cell lines. BCa cell lines HTB-9, HTB-5, RT-4, T24 and HT-1376 and benign urothelial UROtsa cells were analyzed for MIF, CD74, and CD44 expression via quantitative PCR or western blot to assess expression of the MIF signaling axis. CD74 and CD44 expression by q-PCR were dramatically elevated in BCa cell lines vs. benign cell lines. Protein levels of CD74 and CD44 were elevated in multiple cell lines as well. MIF expression levels did not change between cell lines. To ascertain differences in BCa tumorigeneis, WT C57Bl/6J mice or CD74-/- mice were given 0.05% BBN in the drinking water for 22 weeks. Bladders were weighed and evaluated for pathologic staging by histology. After exposure to BBN, bladders from CD74-/- mice had a 33% reduction in weight vs. WT bladders (p=.062). Pathological analysis revealed lower stage tumors in bladders of CD74-/- mice (33% incidence; 6.7% pTa, 0% pTis, 6.7% pT1, 20% pT2, 6.7% pT3) as compared to bladders of WT mice (81.3% incidence; 0% pTa, 6.3% pTis, 25% pT1, 12.5% pT2, 37.5% pT3), which was a statistically significant reduction in tumor stage. Lower tumor stage correlated significantly with the CD74-/- genotype (p=0.02, Fisher's Exact Test). These data suggest CD74 likely mediates a portion of the effects of MIF in BCa, raising the possibility of both CD74 dependent, and independent MIF signaling pathways. Citation Format: Justin Penticuff, Sambantham Shanmugam, Joshua Warrick, Brian Chase, Erika Abbott, Benjamin L. Woolbright, John A. Taylor. Targeting the MIF receptor CD74 in bladder cancer tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3560.
Abstract 13775: Clinical Significance of Flow Energy Loss inside the Left Ventricle via Cardiovascular Magnetic Resonance in Non-ischemic Dilated Cardiomyopathy
Authors: TakeruNabeta, KeiichiItatani, YuichiroIida, YukiIkeda, SyunsukeIshii, TakashiNaruke, HisahitoShinagawa, TakayukiInomata, KagamiMiyazi, JunyaAko
Journal: Circulation (2014)

Background: Blood flow patterns are closely linked to the morphology and function of the cardiovascular system and its efficiency can be estimated with flow energy loss (FEL). We have made it passible to measure FEL by using 2D cine phase-contrast (PC) cardiac magnetic resonance (CMR) technique. The object of the present study is to reveal the relationship of the clinical parameter and FEL in patients with non-ischemic dilated cardiomyopathy (DCM). Methods: A cross-sectional study was carried out on patients with DCM. All patients underwent CMR technique including late gadolinium enhancement (LGE). Intramural geometry was extracted with Steady-state free precession series, and PC-CMR was superposed. Blood flow was visualized and FEL with viscous dissipation was calculated in-house code. Results: A total of nineteen such patients were included in this study. FEL inside the left ventricle (LV) was 331 ± 117 mW/m2 (range 188-626). FEL was significantly correlated with age (r = -0.53, P = 0.02) and LV end-dia...
Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling
Authors: WataruShioyama, YoshikazuNakaoka, KaoriHiguchi, TakashiMinami, YoshiakiTaniyama, KeigoNishida, HiroyasuKidoya, TakashiSonobe, HisamichiNaito, YohArita, TakahiroHashimoto, TadashiKuroda, YasushiFujio, MikiyasuShirai, NobuyukiTakakura, RyuichiMorishita, KeikoYamauchi-Takihara, TatsuhikoKodama, ToshioHirano, NaokiMochizuki, IsseiKomuro
Journal: Circulation Research (2011)

Rationale:Grb2-associated binder (Gab) docking proteins, consisting of Gab1, Gab2, and Gab3, have crucial roles in growth factor–dependent signaling. Various proangiogenic growth factors regulate angiogenesis and endothelial function. However, the roles of Gab proteins in angiogenesis remain elusive. Objective:To elucidate the role of Gab proteins in postnatal angiogenesis. Methods and Results:Endothelium-specific Gab1 knockout (Gab1ECKO) mice were viable and showed no obvious defects in vascular development. Therefore, we analyzed a hindlimb ischemia (HLI) model of control, Gab1ECKO, or conventional Gab2 knockout (Gab2KO) mice. Intriguingly, impaired blood flow recovery and necrosis in the operated limb was observed in all of Gab1ECKO, but not in control or Gab2KO mice. Among several proangiogenic growth factors, hepatocyte growth factor (HGF) induced the most prominent tyrosine phosphorylation of Gab1 and subsequent complex formation of Gab1 with SHP2 (Src homology-2–containing protein tyrosine phosphat...
Abstract 2533: Regulation of proliferation and metastasis gene expression by DAX-1 (<i>NR0B1</i>) in human breast cancer cells
Authors: Christina Tzagarakis-Foster
Journal: Cancer Research (2018)

Abstract The orphan nuclear receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, critical region on the X chromosome, gene 1) is known to serve an important role early on in mammalian sex determination as well as in the regulation of expression of steroid hormones. While it is unclear whether DAX-1 functions independently, DAX-1 has been demonstrated to act as a repressor of many nuclear hormone receptors, including ER, AR, PR, LRH-1 and SF-1. DAX-1 plays a role in select adult tissues, including gonadal tissue. However, it has also been shown to play a role in several types of cancer, though its specific function is not well understood. For example, in some types of cancer DAX-1 expression is upregulated, while in other cancers it is highly downregulated or completely absent. In an effort to better understand DAX-1 function both in normal and disease states, we examined the actions of DAX-1 in MCF7 breast cancer cells, which do not express the DAX-1 gene. We probed three different PCR arrays (breast cancer genes, proliferation genes and metastatic genes) to determine which genes were influenced by DAX-1 expression. With the introduction of DAX-1 in ERα positive breast cancer cells (MCF-7), we find that DAX-1 inhibits cell proliferation and blocks estradiol activation of key cell cycle regulatory genes, such as cyclin D1, as well as important metastatic genes. We show that DAX-1 binds directly to ERα and the ERα-DAX-1 complex binds to the cyclin D1 promoter. The outcome of DAX-1 expression in MCF7 cells is cell cycle arrest through the repression of key cell cycle regulatory genes. These results demonstrate that DAX-1 functions as a corepressor of ERα in MCF7 breast cancer cells by preventing the activation of growth-promoting genes and decreasing cell proliferation in response to estrogens. These findings could have significant implications for future drug development strategies specifically aimed at ER-interacting proteins such as DAX-1. Citation Format: Christina Tzagarakis-Foster. Regulation of proliferation and metastasis gene expression by DAX-1 (NR0B1) in human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2533.