tbuckley/cabot-search huggingface dataset:
Abstract 1375: Contrasting effects of VEGF pathway inhibitors in primary and metastatic disease using perioperative neoadjuvant mouse models
Authors: John M.L. Ebos, Christina R. Lee, William Cruz-Munoz, Christopher Jedeszko, Robert S. Kerbel
Journal: Cancer Research (2012)

Abstract Recent clinical trial failures with antiangiogenic therapy in patients with early-stage disease have raised the possibility that drug efficacy in preclinical studies, typically involving models of localized primary grown tumors, may not always predict for efficacy in treating metastatic disease, which is the most common cause of mortality in patients. Moreover, depending on disease stage and treatment circumstances, the efficacy of VEGF-pathway inhibitors administered as monotherapies may be offset in certain settings by increased aggressive invasiveness and augmented metastatic potential. Thus, with hundreds of trials underway in neoadjuvant and adjuvant settings to evaluate the efficacy of antiangiogenic therapy in blocking or slowing micrometastatic disease and eventual tumor recurrence, there is an urgent need clarify the utility of such drugs in all stages of tumor progression. Herein we describe a novel preclinical neoadjuvant therapeutic methodology used to compare the effects of short-term VEGF pathway inhibition in highly metastatic human breast, melanoma, and kidney tumor cells grown orthotopically in SCID mice before and after surgical resection. While cytotoxic chemotherapy administered in the maximum tolerated dose could slow tumor growth and lead to a prolongation of survival after resection, similar significant benefits by various VEGF inhibitors in primary tumor inhibition did not consistently translate into significant prevention of recurrent local and distant metastasis after treatment cessation. Furthermore, reductions in primary tumor growth by neutralizing antibodies to VEGF or VEGFR-2 were more predictive of modest survival benefits after tumor resection, compared to the VEGFR tyrosine kinase inhibitor (TKI) sunitinib, which had either no effect or decreased survival compared to control - despite significant reductions in primary tumor growth after neoadjuvant treatment. Potential tumor-independent ‘host’ drug responses could account for this difference as short-term treatment of immunocompromised nu/nu mice prior to intravenous tumor inoculation lead to modest or negligible benefits with VEGF or VEGFR2 antibodies compared to worse outcomes in VEGFR TKI pre-treated animals. Taken together, preclinical neoadjuvant therapy allows for the distinction of ‘anti-primary’ and ‘anti-metastatic’ effects and may serve as a predictive tool to model ongoing clinical trials as well as indicate potential drug combinations which may be used to overcome limitations when such drugs are used as a monotherapy. 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 1375. doi:1538-7445.AM2012-1375
Abstract 4430: Protective effects of rebamipide liquid on radiation-induced glositis in rats.
Authors: Takako Nakashima, Naoya Uematsu, Masafumi Shibamori, Kazushi Sakurai, Masayuki Sato, Takakuni Matsuda, Nobutomo Sako
Journal: Cancer Research (2013)

Abstract [Background &amp; Aims] Rebamipide is widely used for mucosal protection, healing of gastric ulcers and treatment of gastritis. Recently, it was reported that Rebamipide gargle inhibited oral mucositis induced by chemoradiotherapy in head and neck cancer patients. In this study, we examined protective effects of Rebamipide Liquid on radiation-induced glossitis rat model and analyzed the expression level of pro-inflammatory cytokines and chemokines in the injury area of tongue. [Materials &amp; Methods] Rebamipide Liquid, comprising with Rebamipide crystals less than 500 nm particles, was prepared by a neutralizing crystallization technique. This formulation is a stable homogenous aqueous suspension provided with appropriate viscosity by adding viscosity enhanced agents to improve the retention in the oral cavity. The glossitis was induced by X-ray with 15Gy irradiation only around the snout (Day 0) in rats. Rebamipide Liquid was administered intraorally at doses of 5, 10 or 20 mg/kg (1, 2 or 4%, respectively), 6 times a day for 14 days from Day -7 to Day 6. These tongue tissue specimens were obtained at Day 7 and their images were recorded by a digital camera for efficacy evaluations. Gene expression analysis was performed with quantitative real-time PCR (ABI) and protein level was evaluated with Bio-Plex system(BioRad) or ELISA in a different study which was conducted at the two doses of 0 and 20 mg/kg (0 and 4%). [Result &amp; Conclusions] The ulcer-like areas (10.8 ± 1.2, 7.9 ± 1.1 and 7.0 ± 0.7%) at doses of 5 - 20 mg/kg (1 - 4%) of Rebamipide Liquid administration, were statistically smaller than the vehicle control at 14.7±1.6%. Another study revealed that the expression of pro-inflammatory cytokines (TNF-α, IL-6 and Il-1β) and chemokines (MCP-1 and Gro-α) were dramatically elevated in the irradiated tongue at Day7, as compared to normal. But these elevated expressions were significantly suppressed by the 4% Rebamipide treatment. These immuoassays elucidated that the production of these cytokines and chemokines were significantly suppressed by the Rebamipide administration. These results demonstrated that the Rebamipide Liquid has a potent pharmacological action for the radiation-induced oral mucositis mediated by the suppression of pro-inflammatory cytokines (TNF-α, IL-6 and Il-1β) and chemokines (MCP-1 and Gro-α). Citation Format: Takako Nakashima, Naoya Uematsu, Masafumi Shibamori, Kazushi Sakurai, Masayuki Sato, Takakuni Matsuda, Nobutomo Sako. Protective effects of rebamipide liquid on radiation-induced glositis in rats. [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 4430. doi:10.1158/1538-7445.AM2013-4430
AB0645 Sarcoid / granulomatous disease in association with helicobacter pylori
Authors: C. B. Colaço, Z. Fattah, P. Charalambous
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Helicobacter Pylori (HP) has been studied in several autoimmune disorders but definite causality is perhaps restricted to MALT Lymphoma and some cases of 'idiopathic' immune thrombocytopenia <sup>(1,2)</sup>. HP may suppress innate immune mechanisms yet promote antigen specific disease in autoimmune gastritis and increase IL 10 producing T- regs <sup>(3)</sup> <h3>Objectives</h3> We postulate a possible link of HP infection to the pathogenesis of granulomatous diseases. <h3>Methods</h3> We report a retrospective review of 7 cases of sarcoidosis / chronic undefined granulomatous disease. <h3>Results</h3> Our index case is of multisystem Sarcoidosis in a 49-year-old Indian male who presented with ANA positive arthropathy, parotid swelling and sicca syndrome. Lip biopsy showed granulomatous inflammation. He was CLO positive on gastric biopsy at OGD and at the onset of HP eradication he deteriorated dramatically with orbital sarcoid myopathy, episcleritis and diplopia. His neurosarcoidosis, and restrictive inflammatory lung disease has responded to steroids. At 18 months systemic features of weight loss fevers and arthralgia/myalgia still require low dose Prednisolone and Mycophenolate. His immediate deterioration concurs with reports of transient arthralgias post HP eradication, possibly due to antigen load. A second case is of 40 year old Indian male, with limited but persistent granulomatous infiltration of a lachrymal gland and no further evidence of Sarcoidosis, had active HP which was eradicated successfully; but he still requires Prednisolone at 4 months. Review of one 41 year old Afro-Caribbean and 3 Asian females ages 51 -70 yrs and a 44 yr old Asian male confirmed active HP infection at the time of diagnosis or history of HP eradication prior to diagnosis of sarcoidosis. Further details of this incidental unique cohort of 3 males and 4 females with granulomatous disease will be presented. <h3>Conclusions</h3> This incidental cohort suggests a role for H Pylori in granulomatous disorders. Reports in RA and Sjögren's have not yet defined a specific mechanism or definite association. We propose H Pylori persistence may trigger or accelerate granulomatous disease by antigen specific or bystander cytokine milieu mechanisms. <h3>References</h3> Wotherspoon, A C ; Ortiz-hidalgo, C ; Falzon, M R ; Isaacson, P G.Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet, 1991, Vol.338(8776), pp.1175-6 Pordeus V, Szyper-Kravitz M, Levy RA, Vaz NM, Shoenfeld Y (2008). Infections and autoimmunity: a panorama. Clin Rev Allergy Immunol 34: 283–299. Mitchell, P J; Afzali, B; Fazekasova, H ; Chen, D ; Ali, N ; Powell, N ; Lord, G M ; Lechler, R I ; Lombardi, G Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1βproduction by dendritic cells Clinical and experimental immunology, 2012, Vol.170(3), pp.300-9 <h3>Disclosure of Interest</h3> None Declared
CONTRAST-INDUCED PATIENT DISCOMFORT: A COMPARATIVE STUDY OF VISIPAQUE (IODIXANOL) INJECTION 320 MG I/ML VERSUS ISOVUE – 370 (IOPAMIDOL INJECTION 76%) FOR PERIPHERAL ARTERIOGRAPHY
Authors: Thomas Todoran, Christian Rosenberg, Jos Joaqun Martnez Rodrigo, Elena Lonjedo Vicent, Juan Macho Fernndez
Journal: Journal of the American College of Cardiology (2014)
THU0573 Association Between Sosiodemogapic Data and Perceived Health Status on Sexual Activity in Patients with Axial Spondyloarthritis
Authors: K. H. Berg, A. Prøven, E. Almås, E. E. P. Benestad, M. Østensen, G. Haugeberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Axial spondyloarthritis (ax-SpA) is a chronic inflammatory disorder causing signs and symptoms from the axial skeleton, but may also affect peripheral joints, tendons and internal organs. Ax-SpA may give rise to significant loss of function and impaired quality of life. Despite the known importance of sexuality as part of quality of life (Healey 2009), only a few studies have explored sexuality in ax-SpA patients. <h3>Objectives</h3> To investigate the association between sosiodemograpic data and perceived health status on sexual activity in patients with ax-SpA. <h3>Methods</h3> Patients with ax-SpA (fulfilling the axial SpA criteria) were consecutively recruited from one clinic in southern and one clinic in eastern Norway. A broad specter of data was collected including demographics, clinical data, and quality of life data including 15D. 15D also contains the question addressing the impact of health on sexual activity with the following response options: My state of health: 1. has no adverse effect on my sexual activity; 2. has a slight effect on my sexual activity; 3. has a considerable effect on my sexual activity: 4. makes sexual activity almost impossible and 5 makes sexual activity impossible. We dichotomized the sexuality question with 5 answers into two groups. Answer 1 and 2 into no or little impact and the answer 3-5 into large impact. Appropriate statistical tests were applied including descriptive and group comparison. <h3>Results</h3> Patients characteristics: Mean (SD) age in the 389 prospectively assessed patients was 46.8 (22.7) yrs and weight was 82.9 (17.4) kg, 66.5% were men, 27.9% were current smoker, 72.3 were at work, 75.5% were married or lived together and 50.8% exercised &gt;3 hrs per week, 34.7% exercised 1-3 hrs per week. Disease duration was in median [IQR] 12.4 [18.5] yrs and 89.9% were HLA-B27+. For disease measures BASDAI was 3.2 (2.1), BASFI 2.7 (2.2), BAS-G 3.9 (2.6), BASMI 2.4 (2.0), HAQ 0.56 (0.49), ESR 14.1 (12.9) mm/hr and median CRP 4.0 [2.6] mg/dl. Current user of NSAIDs was 44.0%, DMARDs 4.9% and biologics 22.6%. In the table the association between selected sociodemographic characteristics and perceived health status on sexual activity is displayed. <h3>Conclusions</h3> Our data reveal that female gender, current smoking, physical activity and work, were associated with a negative effect on perceived health status on sexuality, whereas living together had no influence. This indicates that sosiodemographic factors are important to adjust for when exploring the impact of the ax-SpA disease on sexuality. <h3>Disclosure of Interest</h3> None Declared
Ultrasonic and Radiographic Cholecystography
Authors: Royal J. Bartrum, Harte C. Crow, Sheila R. Foote
Journal: New England Journal of Medicine (1977)

To define the relative merits of radiographic and ultrasonic cholecystography, we studied 208 randomly selected patients with possible cholelithiasis. The patients underwent both procedures, and the results were interpreted in blind fashion. Two hundred patients had satisfactory confirmation of their diagnosis, by either a well visualized radiographic cholecystogram or operation or both. The overall accuracy of the ultrasonic examination was 93 per cent, with a false-negative rate of 11 and an indeterminate rate of 4 per cent. The indeterminate rate was 24 per cent for the single-dose oral cholecystogram and 8 per cent for the double-dose oral cholecystogram. Both ultrasonic cholecystography and radiographic cholecystography are useful to detect gallstones. Our findings support using single-dose oral cholecystography as the routine first examination. If the gallbladder is not satisfactorily visualized, ultrasonic cholecystography can be performed immediately. In an emergency or for patients who might be pregnant, ultrasonic cholecystography is available as the initial examination. (N Engl J Med 296:538–541, 1977)
Abstract P2-20-01: Safety and Clinical Efficacy of Multiple Booster Inoculations with the E75 Adjuvant Breast Cancer Vaccine
Authors: TJ Vreeland, GT Clifton, R Patil, KS Clive, AK Sears, JP Holmes, EA Mittendorf, S Ponniah, GE. Peoples
Journal: Cancer Research (2010)

Abstract Background: We are conducting clinical trials of the HER2/neu E75-peptide+GM-CSF vaccine in clinically disease-free breast cancer patients at high risk for recurrence. Our Phase I/II trials have shown that the vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8+ T-cells; however, this peptide-specific immunity decreases over time. Due to this waning immunity, a voluntary booster program was initiated. Methods: Node-positive and high-risk node-negative patients who were clinically disease-free after surgery and standard adjuvant therapy were enrolled. HLA-A2/A3+ patients were vaccinated (VG), while HLA-A2/A3-patients were followed as controls (CG). Patients who were ≥6 months from the completion of their primary vaccination series (PVS) were offered booster inoculations every 6 months. Patients were monitored for local and systemic toxicity. Orthagonal mean of local reactions (LR) were measured after each booster inoculation. In HLA-A2+ patients, E75-specific CD8+ T-cells were quantified using the HLA-A2:IgG dimer immediately before and 1 month after each booster administration. Patients were monitored clinically and radiographically for recurrences. Results: 188 patients were enrolled (109 VG, 79 CG). Fifty-three of the VG patients received at least one booster (B1), with 33 receiving a second booster (B2), and 20 a third booster (B3). Booster inoculations were well-tolerated with only grade 1 and 2 local and systemic toxicities. Compared to the LR at the end of the PVS (mean = 82±3mm), the mean LR increased at B1 (88±3 mm, p=0.13), B2 (94±6, p=0.02), and B3 (93±10 mm, p=0.04). Average CD8+ E75-specific T-cells did not change significantly prebooster (1.1±0.1%) compared to post-B1 (1.1± 0.1%, p=0.71) or post-B2 (1.4±0.2%, p=0.27) but did increase significantly post-B3 (2.4±0.3%, P&amp;lt;0.01). Additionally, the percentage of HLA-A2+ patients with significant residual immunity (defined as &amp;gt;0.5% CD8+E75-specific T cells) increased from pre-booster (29/43, 67%) to post-B3 (16/16, 100%; p=0.01). With 24 month clinical follow-up complete in all enrolled patients, there has been a nonsignificant decrease in recurrences observed in the VG compared to the CG (6.5% vs 13.1%, p=0.19), with no recurrences in patients who had received at least one booster inoculation by 24 months (0/40, 0%, vs 13.1% in CG, p=0.03). Conclusions: The HER2/neu E75 peptide vaccine stimulates immunity that is maintained or increased with booster inoculations in disease-free breast cancer patients. The booster inoculations are safe, with minimal toxicity. The clinical efficacy of the E75 vaccine with booster inoculations will be further evaluated in a phase III trial. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-20-01.
Serum Cholesterol And Cancer: Is There A Connection?
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Serum Cholesterol And Cancer: Is There A Connection? Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1863–1865, https://doi.org/10.1093/jnci/81.24.1863 Published: 20 December 1989
Sex Differences in Academic Advancement — Results of a National Study of Pediatricians
Authors: Sherrie H. Kaplan, Lisa M. Sullivan, Kimberly A. Dukes, Carol F. Phillips, Robert P. Kelch, Jane G. Schaller
Journal: New England Journal of Medicine (1996)

Although the numbers of women in training and in entry-level academic positions in medicine have increased substantially in recent years, the proportion of women in senior faculty positions has not changed. We conducted a study to determine the contributions of background and training, academic productivity, distribution of work time, institutional support, career attitudes, and family responsibilities to sex differences in academic rank and salary among faculty members of academic pediatric departments.We conducted a cross-sectional survey of all salaried physicians in 126 academic departments of pediatrics in the United States in January 1992. Of the 6441 questionnaires distributed, 4285 (67 percent) were returned. The sample was representative of U.S. pediatric faculty members. Multivariate models were used to relate academic rank and salary to 16 independent variables.Significantly fewer women than men achieved the rank of associate professor or higher. For both men and women, higher salaries and ranks were related to greater academic productivity (more publications and grants), more hours worked, more institutional support of research, greater overall career satisfaction, and fewer career problems. Less time spent in teaching and patient care was related to greater academic productivity for both sexes. Women in the low ranks were less academically productive and spent significantly more time in teaching and patient care than men in those ranks. Adjustment for all independent variables eliminated sex differences in academic rank but not in salary.Lower rates of academic productivity, more time spent in teaching and patient care and less time spent in research, less institutional support for research, and lower rates of specialization in highly paid subspecialties contributed to the lower ranks and salaries of female faculty members.
P5-06-01: Gene Expression Analysis of Resistance to Bevacizumab in a VEGF-Reinforced Xenograft Model of ER-Positive Breast Cancer.
Authors: Y Gökmen-Polar, RA Toroni, C Goswami, KL Sanders, R Mehta, U Sirimalle, B Tanasa, C Shen, L Li, M Ivan, S Badve, GW Sledge
Journal: Cancer Research (2011)

Abstract Background: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), had promising therapeutic efficacy in breast cancer. However, intrinsic or acquired resistance is common in the clinic. To improve our understanding of the underlying mechanisms of resistance to bevacizumab (BEV), we report the gene expression analysis of resistance to bevacizumab in a VEGF-overexpressing xenograft model of ER-positive breast cancer. Methods: We developed a nude mouse xenograft model of resistance to anti-VEGF therapy with BEV in which MCF-7 control (ML20) or MCF-7 VEGF (MV165) transfectants were implanted in mammary fat pads, allowed to grow, then treated with BEV, with collection of tumor at early or late time points (while responding (R) to or progressing (NR) on anti-VEGF therapy). To elucidate differentially expressed gene profiling associated with tumor resistance to BEV, we performed whole-genome gene expression analysis (Human WG-6v2 Expression Beadchips, Illumina) and miRNA profiling (TaqMan ***ArrayHuman MicroRNAA+B Cards Set v3.0, Applied Biosystems). Validation of the chosen genes was performed using quantitative real-time RT-PCR (qRT-PCR). Results: Gene expression analysis revealed differentially regulated genes in the MV165-NR group compared with the MV165-R group. Among the significant genes, Follistatin (FST) and HEY2 were the top genes upregulated in NR compared to R by ANOVA. Expression of HEY2 is induced by the Notch signaling pathway. Using qRT-PCR, we validated the expression of FST and Notch in our system. FST was significantly decreased (Fold change= −3.2; P=0.03) in the R group compared with vehicle in MV165 xenografts. In contrast to R group, FST was upregulated significantly (Fold change= 9.3; P=0.05) in the NR group. Notch4 displayed increased levels of expression in NR group, but it did not reach significance (P=0.23). In addition, correlation of mRNA and miRNA profiles showed that miRNAs targeting FST and Notch4 were differentially regulated in NR group compared to R group in MV165 xenograft tumors. Among the miRNAs, TGF-β-induced oncomiR miR-181a is up-regulated in NR and targets both FST and Notch4. Other miRNAs that target both Notch4 and FST include miR-1, miR-133a, miR-133b, and mir-449b. Conclusion: Our data serve as a potential mechanistic explanation for acquired resistance to bevacizumab. These data may shed light on the transitory effect of BEV observed in the E2100 firstline metastatic breast cancer trial, where VEGF-targeted therapy prolongs progression-free survival in metastatic breast cancer without improving overall survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-06-01.
P1252 EVEROLIMUS HALTS DISEASE PROGRESSION IN A RODENT MODEL OF POLYCYSTIC LIVER DISEASE: RESULTS OF A LONGITUDINAL MRI-STUDY
Authors: F. Temmerman, F. Chen, J. van Pelt, D. Mekahli, E. Levtchenko, Y. Ni, F. Nevens
Journal: Journal of Hepatology (2014)
Life-threatening bleeding following Barrett’s surveillance biopsies
Authors: J. Mannath, V. Subramanian, P. Kaye, K. Ragunath
Journal: Endoscopy (2010)

A fit 88-year-old man attended for Barrett's esophagus (BE) surveillance endoscopy. He was initially referred to our centre in 2008 with a diagnosis of high grade dysplasia (HGD) based on random biopsies at a district general hospital. He underwent an uneventful endoscopic mucosal resection for a visible flat lesion (Paris 0-IIa) located 30 cm from the incisors. The need and appropriateness of continuing surveillance [1] was discussed with him, considering his age and comorbidity (hypertension, for which he was taking calcium channel blockers and aspirin [75 mg]). He had a good functional status (American Society of Anesthesiologists [ASA] grade 2) and he wished to continue surveillance. Trimodal endoscopy (high-resolution endoscopy, autofluorescence imaging, and narrow band imaging) revealed a flat area suspicious for dysplasia above the gastroesophageal junction at 35 cm ([Figs. 1 3]).