tbuckley/cabot-search huggingface dataset:
Abstract 2401: Loss of Nkx3.1 cooperates with Myc overexpression to promote prostate tumorigenesis
Authors: Sydika McKissic, Meejeon Roh, Sarki Abdulkadir
Journal: Cancer Research (2011)

Abstract Nkx3.1 is a homeodomain-containing transcription factor essential for prostate development and differentiation while loss mediates prostate tumor initiation. In mice, conditional loss of Nkx3.1 results in prostatic epithelial hyperplasia and prostatic intraepithelial neoplasia (PIN) formation. This increases the susceptibility of mice with compound mutations to the development of invasive adenocarcinoma. Human clinical data suggests that loss of Nkx3.1 and Myc overexpression are strongly correlated with increased tumor stage. Furthermore, Myc overexpressing transgenic mice lose Nkx3.1 in the PIN to carcinoma transition suggesting that Nkx3.1 loss is distinct and may provide a selective growth advantage. To further evaluate the cooperation between Nkx3.1 and Myc, we generated transgenic mice with prostate specific loss of Nkx3.1 and Myc overexpression. These mice contain a latent, Cre-activatable Myc allele and Nkx3.1 floxed alleles. Prostate specific Cre results in concurrent deletion of Nkx3.1 and activation of Myc. We have found that the young trigenic mice show advanced lesions compared to controls. High grade prostate intraepithelial neoplasia (HGPIN) was evident as early as 15 weeks of age. By 35 weeks of age, these mice show multi-focal HGPIN lesions with micro-invasive cancer. An increase in proliferation and a modest increase in apoptosis are also seen. Complementary prostate regeneration studies further support this progressive phenotype. We hypothesize that Nkx3.1 and Myc are cooperating to promote prostate tumorigenesis by regulating important cancer genes. Future studies are being conducted to identify the mechanism of cooperation between Nkx3.1 and Myc. 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 2401. doi:10.1158/1538-7445.AM2011-2401
Intractable Chronic Lymphocytic Leukemia
Authors: R. SCHREK
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Intractable Chronic Lymphocytic Leukemia Get access ROBERT SCHREK ROBERT SCHREK Research Service Veterans Administration HospitalHines, IL 60141 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 8, 15 June 1988, Page 604, https://doi.org/10.1093/jnci/80.8.604 Published: 15 June 1988
FRI0017 How Age, Gender and Body Mass Index Affect the Erythrocyte Sedimentation Rate and the C-Reactive Protein in Early Rheumatoid Arthritis
Authors: L. Siemons, P.M. ten Klooster, H.E. Vonkeman, P.L. van Riel, C.A. Glas, M.A. van de Laar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are two commonly used indirect measures of the extent of inflammation in rheumatoid arthritis (RA). As current RA treatment guidelines strongly emphasize early and aggressive treatment aiming at fast remission, optimal measurement of inflammation in this patient group is becoming increasingly important (Combe et al., 2007; Smolen et al., 2010). However, although dependencies with age, gender, and body mass index have been shown for both inflammatory markers, it remains unclear which inflammatory marker is least affected by these effects in patients with early rheumatoid arthritis. <h3>Objectives</h3> To determine which inflammatory marker, the ESR or CRP, is least affected by age, gender, and BMI in patients with early RA. <h3>Methods</h3> Baseline data from 589 patients from the DREAM registry were used for analyses. Associations between the inflammatory markers and age, gender, and BMI were evaluated first using univariate linear regression analyses. Next, it was tested whether these associations were independent of a patient9s current disease activity (as measured with the other core components of the DAS28) as well as of each other using multiple linear regression analyses with backward elimination. The strengths of the associations were compared using standardized beta (β) coefficients. <h3>Results</h3> Both ESR and CRP were univariately associated with age, gender, and BMI, although the association with BMI disappeared in multivariate analyses. ESR and CRP concentrations significantly increased with age (β-ESR=0.017, <i>p</i>&lt;0.001 and β-CRP=0.009, <i>p</i>=0.006), independently of the number of tender and swollen joints, patient-reported wellbeing, and gender. Furthermore, women demonstrated average ESR levels that were significantly higher than that of men (β=0.198, <i>p</i>=0.007), whereas men had higher CRP levels (β=-0.182, <i>p</i>=0.048). The effects were shown to be strongest on the ESR. <h3>Conclusions</h3> Age and gender are independently associated with the concentrations of both acute phase reactants in early RA, emphasizing the need to take these external factors into account when interpreting disease activity measures. <h3>References</h3> Combe B, Landewe R, Lukas C, Bolosiu HD, Breedveld F, Dougados M, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007;66(1):34-45. Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631-7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5202
Vinorelbine (VNR) and concurrent thoracic radiation therapy (TRT) in locally advanced non-small cell lung cancer (NSCLC)
Authors: L. I. Portalone, A. Lombardi, F. Lucà, M. Signora
Journal: Journal of Clinical Oncology (2008)

18507 Background: A retrospective analysis was performed to evaluate Therapeutic Index of VNR with concurrent TRT in pts with stage III unresectable NSCLC after induction therapy with platinum compounds, gemcitabine and/or vinorelbine. Methods: Multimodality treatment consisted of induction therapy with platinum (80 mg/m2/i.v.) or carboplatinum (AUC 5) plus gemcitabine (1,200 mg/m2/i.v.) (GP) or vinorelbine (25 mg/m2/i.v.) (VP) on days 1–8-21. Patients in complete remission (CR), partial remission (PR) and stable disease (SD) after induction therapy, concomitant chemo-radiotherapy were treated with VNR os (12 mg/m2) or i.v. (5 mg/m2) three-times weekly 2 hours before concurrent TRT (2 Gy/day for 6 wks). Results: From November 2002 to March 2007, 31 chemotherapy and radiotherapy-naive pts were treated (males/females 16/15); median age 60.0 years (range 18 to 77); median ECOG PS 0 (range 0–1); no weight loss > 10% in all pts; stage IIIA 6 pts (19.3%), IIIB 25 pts (80.7%). 21 Pts showed 6 WHO grade III toxic events (7.9%) and 1 WHO grade IV (1.3%) hematologic. After induction therapy we observed the following: 12 partial responses (38.7%) and 19 stable diseases (61.3%). After concurrent radio- chemotherapy clinical responses were as follows: 13 partial response (43.3%), 13 stable disease (43.3%) and 4 progressive disease (13.4%). Toxicity observed was as follows: 1 patient with dysphagia WHO grade III and 1 WHO grade IV, no toxic deaths have occurred. OS was 15.3 months (range 4.4 to +60.3), median TTP 10 months (range 3.7 to 26,1). By stratifying patients in stage IIIA and IIIB at diagnosis, in stage IIIA S was 21.6 months (range 13.5 to +39.2 months) and TTP was 13.9 months (range 11.5 to +19.4 months), in stage IIIB S 14.6 months (range 4.4 to +60.3 months) and TTP 9.1 months (range 3.7 to 26.1 months). After the multimodality treatment 5 patients (16.6%) were submitted to thoracic surgery: at the diagnosis 3 patients were stage IIIA and 2 patients IIIB. Actuarial survival curve shows that at 1 year the probability was 65% and at 2 years 35%. At this writing 9 pts (29%) were alive. Conclusions: Preliminary results of this multimodality treatment are promising as concern activity, local control of disease, median and overall survival. A larger accrual and a longer follow-up will be required to verify these data. No significant financial relationships to disclose.
P4-12-14: Pilot Study Utilizing Fluorine-18 Fluorodeoxyglucose (F-18 FDG) Positron Emission Tomography–Computed Tomography Scan (PET-CT Scan) To Investigate Brain Metabolic Changes during Treatment in Women with Breast Cancer.
Authors: S Virani, R Lagos, G Hobbs, G Marano, G Nagaiah, J Abraham
Journal: Cancer Research (2011)

Abstract BACKGROUND: Approximately 25% of the patients undergoing chemotherapy develop cognitive changes. Similarly, significant neurocognitive changes in verbal memory and executive functioning have been reported in patients undergoing endocrine therapy. Though extensively studied, specific changes in the brain associated with cognitive dysfunction are still not clear. We performed an IRB-approved retrospective pilot study utilizing brain images from standard PET-CT scans in patients being treated for breast cancer. Comparison was made between patients initial and follow-up scans to look for metabolic changes. MATERIALS AND METHODS: Thirty nine patients with a diagnosis of breast cancer were identified from radiology database of West Virginia University Hospitals, who underwent at least two PET-CT scans during their treatment for breast cancer from 2004–2009. Patients with brain metastasis were excluded. NeuroMIM® software analysis program was used to compare a comprehensive database of physiologic brain anatomy and metabolism with F-18 FDG perfusion brain images from the patients. Comparison was made in sixty-three defined brain regions. For each patient, two scans at approximately twelve month intervals were analyzed. The data sets from initial scans were compared with the follow up. RESULTS: A total of 37 patients received cytotoxic chemotherapy, 2 patients received only endocrine therapy. Data analysis using the signed-rank test shows that the collective Z-score values change between the initial and follow up scans. When data analysis is applied to the individual brain regions, the Lingual Gyrus (p=0.012) and the Angular Gyrus (p=0.056)show statistically significant and near significant decreases in brain metabolism respectively. These regions are attributed with language, mathematics and cognition. Several additional regions such as the fusiform gyrus and the primary visual cortex show p-values between 0.05 and 0.10, which indicate “trending”. These regions may demonstrate statistically significant decrease in metabolism if the sample size is increased. DISCUSSION: The Lingual and the Angular Gyrus show a statistically significant and near significant decrease in glucose metabolism respectively, in patients receiving treatment for breast cancer. Limitations of this study include lack of baseline brain imaging and its clinical correlation with cognitive function. Based upon these preliminary findings prospective studies are being planned. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-14.
Detection of Multiple Hepatic Metastases of Gastrinoma Not Apparent on CT By In-111 Octreotide Scintigraphy
Authors: G. F.X. McINERNEY, H. CARMALT, M. MaGEE, K. ALLMAN, H. VAN DER WALL
Journal: Clinical Nuclear Medicine (1996)

A 78-year-old man had watery diarrhea and recurrent peptic ulceration. Extensive investigation disclosed a markedly elevated serum gastrin level and a 3-cm-diameter tumor arising from the head of the pancreas. The patient underwent a laparotomy that confirmed a gastrinoma. No metastases were evident at surgery or on the preoperative CT and MRI. Two years later, the patient presented with recurrence of diarrhea and mild elevation of serum gastrin was noted. The results of two CT scans were both normal. An In-111 Octreotide scan was performed that demonstrated at least seven hepatic metastases. Retrospective analysis of the CT scan revealed a subtle, low-density lesion consistent with metastasis in one of the slices.
FRI0347 Tubastatin A, A Selective Histone Deacetylase-6 Inhibitor, Suppresses Synovial Inflammation and Joint Destruction in A Collagen Antibody-Induced Arthritis Mouse Model
Authors: J. Lee, H. Jeong, I.Y. Kim, J. Hwang, H. Kim, C.H. Jeon, H.-S. Cha, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Histone deacetylases (HDAC) play a key role in regulating gene expression by deacetylasing histones, and HDAC inhibitors induce various cellular effects, including apoptosis, cell cycle arrest and inhibition of angiogenesis. Tubastatin A is a potent and selective HDAC-6 inhibitor and its anti-rheumatic effect has not been determined. <h3>Objectives</h3> This study was undertaken to investigate the effect of Tubastatin A on synovial inflammation and joint destruction in collagen antibody-induced arthritis (CAIA) mouse model. <h3>Methods</h3> CAIA mice were given daily intraperitoneal injections of various concentration of Tubastatin A (0, 10, 50, 100mg/kg, n=6 each). Clinical score, paw thickness, and body weight were measured for 14 days. On day 15, mice were sacrificed and the expression of TNF-α, IL-1, IL-6 from the serum was analyzed using ELISA. Hind foot was examined histologically and synovitis was scored by 2 independent pathologists. Micro CT of the joints was performed and joint destruction was quantified. Cell viability and the expression of inflammatory cytokines in human fibroblast-like synoviocytes (FLS) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3μM) were measured using MTT assay and ELISA, respectively. <h3>Results</h3> In the Tubastatin A-treated group, clinical arthritis was attenuated and paw thickness was lower and this effect was statistically significant in the Tubastatin 100mg/kg group compared to control (p&lt;0.01). All mice lost a small amount of weight but the difference was not statistically significant between groups. In the Tubastatin A 100mg/kg group, the histological severity of synovial inflammation as measured by synovial hypertrophy, density of resident cells, and inflammatory cell infiltrates was significantly lower compared with control (p&lt;0.01, each). In addition, micro CT showed that joint destructions as measured by bone volume/tissue volume and bone surface area/bone volume were significantly less in the Tubastatin 100mg/kg group compared with control (p&lt;0.05). Among pro-inflammatory cytokines, expression of IL-6 in the serum was significantly lower in the Tubastatin A 50mg/kg group compared with control (p&lt;0.05). The expression of IL-6 from human FLS after incubation with Tubastatin A decreased in a dose-dependent manner without affecting the cell viability. <h3>Conclusions</h3> Our data demonstrated that Tubastatin A, a selective HDAC6 inhibitor, ameliorates synovial inflammation and protects against joint destruction in CAIA mice, and reduced expression of IL-6. Our data suggest that Tubastatin A warrant further investigation as a potential therapeutic agent in rheumatoid arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3467
Dose Escalation of Radioantibody in a Mouse Model With the Use of Recombinant Human Interleukin-1 and Granulocyte-Macrophage Colony-Stimulating Factor Intervention to Reduce Myelosuppression
Authors: R D Blumenthal, R M Sharkey, D M Goldenberg
Journal: JNCI Journal of the National Cancer Institute (1992)

In previous studies in a tumor-bearing hamster model, we demonstrated protection and rescue from radio-antibody-induced hematopoietic toxicity by treatment with interleukin-1 (IL-1) before or after radioantibody treatment, as well as attenuation of duration of myelosuppression by administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study was to evaluate the ability of recombinant human IL-1 and recombinant murine GM-CSF to reduce myelosuppression and increase survival of non-tumor—bearing, female BALB/c mice while escalating the maximal tolerated dose (MTD) of radioantibody—the highest dose that results in no deaths. We administered IL-1 for 7 days at 1 × 10 3 U twice a day and GM-CSF starting on the same day for 12 days at a dose of 0.5 μg twice a day, alone or in combination. The doses of iodine 131 ( 131 I)-NP-4 IgG (anti-carcinoembryonic antigen monoclonal antibody) radioantibody used were 270, 340, and 370 μCi; the MTD in mice is 270 μCi. The 12-day schedule of cytokine administration was initiated at various times with respect to the radioantibody dose: on the same day; 6 or 3 days before radioantibody; or 3, 6, or 9 days after radioantibody. Treatment efficacy was measured by survival and white blood cell and platelet counts. A 25% increase to 340 μCi of radioantibody used alone resulted in 100% lethality within 25 days of treatment. The optimal cytokine schedule was a 12-day treatment with the combination of cytokines initiated 3 days before radioantibody. This treatment resulted in 100% survival and significantly reduced the magnitude and duration of hematopoietic toxicity. The increase in radioantibody dose resulted in an 85%–95% decrease in peripheral white blood cells and a 75%–85% reduction in platelets within 14 days of radioantibody administration. Further dose escalation to 370 μCi of radioantibody used alone (37% increase above the MTD) resulted in lethality to 12% of the mice. IL-1 or GM-CSF alone was minimally effective. These studies are the first demonstration that cytokines could be used to reduce radioantibody-induced leukopenia and thrombo-cytopenia and to escalate the tolerated dose of radioantibody by 25%. We plan to evaluate the potential therapeutic benefit of a 25% increase in radioantibody dose in a tumor-bearing mouse model. [J Natl Cancer Inst 84:399–407, 1992]
EUS is superior to CT scan for the detection of the Hepatoma: Results of Prospective Controlled Study
Authors: P Singh, R Erickson, P Mukhopadhyay, A Khan, T Westblom
Journal: Endoscopy (2006)

Aims: Early detection of Hepatocellular Carcinoma (HCC) and the accurate determination of number of lesions are critical in determining eligibility for liver transplantation. CT and MRI often miss small lesions.
CBIO-05UNDERSTANDING AND TACKLING PARACRINE SIGNALING CUES BETWEEN GLIOMA AND IMMUNE CELLS TO THWART GLIOMA INVASIVENESS AND ANGIOGENESIS
Authors: Kan Lu, Dolores Hambardzumyan, Gabriele Bergers
Journal: Neuro-Oncology (2015)

Glioblastoma multiforme (GBM) is the most belligerent adult brain tumor, which is defined by its aggressive growth due to uncontrolled cellular proliferation, resistance to apoptosis, diffuse infiltration and invasion, propensity for necrosis and hypoxia, and vigorous angiogenesis. Recurrence of these invasive tumors is inevitable despite advanced multimodal therapy with surgery followed by radiation and temozolomide treatment resulting in a dismal median survival of beyond one year. A recent milestone in glioma research has been the revelation that therapies targeting other cell types besides tumor cells; i.e., the cell constituents of the vascular niche can convey substantial improvements in radiographic response, progression-free survival, and quality of life. The changing perspective on the environment as a functional contributor represents a profound shift in the approach to biology and therapeutic decisions in GBM. Here, by studying paracrine signaling cues of intratumoral myeloid cells in the perivascular tumor niche and microglial cells in the invading tumor niche we found that these two immune cell populations have distinct and different functions with microglial cells playing a pivotal role in tumor cell invasiveness while intratumoral myeloid cells regulate angiogenesis and tumor survival. Importantly, blocking immune cell-tumor cell paracrine signaling cues endorsed an immunestimulatory and angiostatic environment and ceased tumor invasiveness.
PTU-034 Double Blind Randomised Controlled Trial Of Magnetically Steerable Gastric Capsule Endoscopy (msgce) Vs. Conventional Gastroscopy For Detection Of Beads In A Porcine Stomach
Authors: MF Hale, I Rahman, K Drew, R Sidhu, SA Riley, P Patel, ME McAlindon
Journal: Gut (2014)

<h3>Introduction</h3> Gastroscopy is uncomfortable for patients and incurs the risks of intubation and sedation. Capsule endoscopy is well tolerated and recently a handheld magnet has been developed to enable steering of the capsule to visualise all areas of the capacious stomach. Our preliminary data suggests that a novice can identify all beads sewn into a porcine stomach within 4 min after 40 consecutive examinations.<sup>1</sup> We performed a double blind randomised controlled trial comparing MSGCE with conventional gastroscopy in the detection of beads in the same model. <h3>Methods</h3> Ex-vivo porcine stomach models were used in a standard housing unit. MSGCE was performed according to a standard protocol using 1000mls of water to distend each stomach and a combination of positional change (head down, 30° left lateral, 30° right lateral) and magnetic control to steer the capsule. Each model was examined in a standard fashion by gastroscopy and subsequently MSGCE using MiroCam Navi (Intromedic Ltd). Two blinded investigators (MFH and IR) competent to perform both procedures were allocated randomly to perform either gastroscopy or MSGCE on each model. This was performed as a non-inferiority study with an expected sensitivity of 90% for both (0 estimated difference), a specificity of 100% and a difference of interest 10 percentage points (i.e., 80% is significantly worse). A sample size of 85 beads was needed to achieve this statistical power. Twelve porcine stomachs were prepared with beads as follows: 2 × 0 beads, 2 × 1 bead, 2 × 2 beads, 2 × 3 beads, 2 × 4 beads, 2 × 5 beads, giving a total of 30 beads. The study was conducted in three rounds, giving a total of 90 beads to be identified. Number of beads identified and procedure duration was recorded. <h3>Results</h3> Gastroscopy correctly identified 88% (79/90) beads, MSGCE correctly identified 89% (80/90) beads and thus is non-inferior to gastroscopy in this setting (95% CI 82.54–95.46%). Mean examination times for gastroscopy and MSGCE were 3.34 min and 9.90 min respectively. MSGCE overestimated the number of beads present on a single occasion. <h3>Conclusion</h3> MSGCE is equivalent to conventional gastroscopy in the detection of beads placed in a porcine stomach model. Procedure duration was longer for MSGCE compared to gastroscopy. Further studies in humans are necessary to define the scope and utility of this exciting new technique. <h3>Reference</h3> Hale MF, Drew K, Baldacchino T, Anderson S, Sanders DS, Riley SA, Sidhu R, McAlindon ME. Gastroscopy without a gastroscope! Feasibility in a porcine stomach model using a magnetic capsule. <i>Abstract. British Society of Gastroenterology Annual Meeting</i>, Jun 2013 <h3>Disclosure of Interest</h3> None Declared.
Influence of non-selective and selective endothelin - 1 receptor antagonists on liver microcirculation in an experimental mouse model of cirrhosis studied by intravital fluorescence microscopy
Authors: Eline Vanheule, Christophe Van Steenkiste, Anja Geerts, Hans Van Vlierberghe, Martine De Vos, Isabelle Colle
Journal: Hepatology (2008)