tbuckley/cabot-search huggingface dataset:
THU0038 Vascular Endothelial Growth Factor (VEGF) Induces Osteoclastogenesis in Rheumatoid Arthritis
Authors: H.-R. Kim, S.-H. Lee, S.-H. Lee, H.-Y. Kim
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Vascular endothelial growth factor (VEGF) has angiogenic, inflammatory and bony destructive roles on rheumatoid arthritis (RA). <h3>Objectives</h3> This study was aimed to determine the unique role of VEGF on the osteoclastogenesis in RA. <h3>Methods</h3> The expression of VEGF, receptor activator of nuclear factor kB ligand (RANKL) and CD55 in RA synovium was determined using confocal microscopy. VEGF and RANKL concentrations in synovial fluid and their correlation were determined using ELISA. VEGF-induced RANKL expression was determined in RA synovial fibroblasts using reverse transcription PCR, luciferase assays and ELISA. Peripheral blood monocytes were cultured with VEGF, and then osteoclastogenesis was assessed by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Osteoclastogenesis was also determined in co-culture of monocytes with VEGF–pretreated synovial fibroblasts. <h3>Results</h3> There was co-expression of VEGF, RANKL and CD55 in the lining and sublining area of RA synovium. RANKL concentration correlated with VEGF concentration in RA synovial fluid. VEGF stimulated the expression of RANKL mRNA and protein in RA synovial fibroblasts. RANKL promoter activity was upregulated by VEGF in the synovial fibroblasts transfected with RANKL reporter plasmids. The VEGF-induced RANKL expression was decreased by the inhibition of both VEGF receptor 1 and 2 pathways. VEGF induced osteoclast differentiation from monocytes in the absence of RANKL. When monocytes were co-cultured with VEGF-prestimulated RA synovial fibroblasts, monocytes were also differentiated into osteoclasts and the osteoclastogenesis decreased with inhibition of Src and PKC pathways. <h3>Conclusions</h3> VEGF plays dual roles on osteoclastogenesis in RA: direct induction of osteoclastogenesis from the precursors and stimulation of RANKL production in synovial fibroblasts, which mediates by Src and PKC pathways. The axis of VEGF and RANKL could be a potential therapeutic target for RA-associated bone destruction. <h3>Disclosure of Interest</h3> None declared
Endostatin: Are the 2 Years Up Yet?
Authors: Jan H. M. Schellens, Mark J. Ratain
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.18.3758 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12228194 Endostatin: Are the 2 Years Up Yet? Jan H. M. SchellensxJan H. M. SchellensSearch for articles by this author Mark J. RatainxMark J. RatainSearch for articles by this author Show More The Netherlands Cancer Institute, Amsterdam, the NetherlandsThe University of Chicago, Cancer Research Center, Chicago, IL https://doi.org/10.1200/JCO.2002.20.18.3758 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Role of Reactive Oxygen Metabolites in Organophosphate-Bidrin-Induced Renal Tubular Cytotoxicity
Authors: VANDANA S. POOVALA, HONG HUANG, ABDULLA K. SALAHUDEEN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Due to low toxicity to nontarget species and rapid degradation after its application, organophosphate (OP) remains a widely used class of pesticide. Suicidal or accidental overdose of OP can result in acute tubular necrosis. Experimental evidence shows little correlation between the renal tubular necrosis and the degree of OP-induced acetylcholinesterase inhibition, the main mechanism of OP's toxicity, suggesting the involvement of alternate mechanisms. Since reactive oxygen species (ROS) are known mediators of many toxin-induced renal injuries, this study was conducted to investigate whether ROS play a role in Bidrin® (BD)-induced renal tubular epithelial cell (LLC-PK 1 ) toxicity. BD is an OP insecticide formulation with dicrotophos as the active ingredient. LLC-PK 1 cell death, determined by lactate dehydrogenase (LDH) release (% of total), rose concentration- and time-dependently after exposure of the cells to 1000, 1250, 1500, 1750, and 2000 ppm of BD for 6, 12, 24, and 48 h. Antioxidants 2-methylaminochroman (2-MAC; 0.3 to 2.5 μM) and desferrioxamine (DFO; 0.25 to 2 mM) reduced cell damage induced by 1250 ppm of BD over a 24-h incubation in a concentration-related manner. The greatest reductions in % LDH were produced by DFO 2 mM and 2-MAC 2.5 μM, both significantly lower than BD alone. H 2 O 2 levels (μmol/mg protein per h) were significantly elevated after exposure to 1250 ppm of BD. Significantly increased malondialdehyde formation (nmol/mg protein) compared with control was also found in BD-exposed cells indicating enhanced lipid peroxidation. Malondialdehyde generation was significantly suppressed by 2-MAC and DFO. These results demonstrate that the organophosphate BD can cause direct tubular cytotoxicity, and implicate, at least in part, a role for ROS and accompanying lipid peroxidation in cytotoxicity. Based on these direct in vitro findings, it is hypothesized that, besides hypotension that often accompanies OP intoxication, OP-induced oxidative stress at the tubular level may play a role in the pathogenesis of acute tubular necrosis.
Abstract 18344: Smoking Worsens the Risk of Oxidative Stress in Individuals With Hepatic Steatosis
Authors: Ebenezer T Oni, Pragya Singha, Shozab S Ali, Jonathan Aboagye, Wasim Muzaik, Michael J Blaha, Arthur A Agatston, Roger S Blumenthal, Raquel D Conceicao, Romeu S Meneghelo, Jose A Carvalho, Raul D Santos, Khurram Nasir
Journal: Circulation (2013)

BACKGROUND: Serum gamma-Glutamyl Transferase (GGT) is a marker of increased oxidative stress and also associated with an increased cardiovascular (CV) risks. The oxidative stress effect of smoking may be aggravated individuals with hepatic steatosis (HS). We aimed to ascertain the effect of smoking on GGT levels in the presence or absence of HS. METHODS: We evaluated 6,373 healthy Brazilian subjects (43±10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. HS was ultrasound diagnosed and smoking was categorized as current smokers or none smokers. RESULTS: The prevalence of NAFLD was 36% (n=2,075) and 564 (9%) were smokers. There was an increasing prevalence of smokers in higher GGT quartiles (q1-19%, q2-24%, q3-25%, q4-32%, p&lt;0.001). As shown in figure below, smoking was associated significantly with higher GGT levels in smokers with HS (p&lt;0.001), whereas no such association was noted among those without HS. In multivariate adjusted model, mean GGT was 11.08 mg/dl higher as compared to non-smoker among those with HS, whereas no such relationship was observed in those without HS. Overall the interaction of HS and smoking for prediction of GGT levels as marker of oxidative stress was statistically significant Conclusions: In this cohort of asymptomatic individuals, smoking significantly raised oxidative stress as measured by GGT level among persons with hepatic steatosis. This suggests smoking worsens the CV risk in individuals with HS. Future studies to ascertain this association is imperative, and may provide a much needed boast to emphasize lifestyle modification among HS individuals.
Brain-Derived Microparticles Induce Systemic Coagulation Associated with Traumatic Brain Injury
Authors: Jing-fei Dong, Ye Tian, Breia Salsbery, Hengjie Yuan, Min Wang, Xiaoping Wu, Zilong Zhao, Barbara A. Konkle, Perumal Thiagarajan, Min Li, Jianning Zhang
Journal: Blood (2014)
Geographic Patterns of Renal Cancer in the United States
Authors: W J Blot, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1979)

Mapping of the geographic distribution of renal cancer mortality for groupings of U.S. counties revealed clustering of elevated rates among white males and females in the upper north-central part of the country. Throughout the United States, mortality increased with urbanization for males only, whereas rates for both sexes showed positive correlations with socioeconomic status. The major correlate of the cancer rates was ethnicity. Mortality was elevated in counties with high percentages of residents of German, Scandinavian, and especially Russian descent. Ethnic susceptibility appears to account, at least partly, for the regional clustering of kidney cancer and may provide leads to environmental determinants.
Agreement between asthma control perception by patients, by physicians and according to guidelines
Authors: M.C. Vennera, C. Picado, L. Herraez, J. Galera, J. Casafont
Journal: European Respiratory Journal (2011)

Background: Despite the clinical interest and current treatments availability, more than a half of Spanish asthma patients fail to control their disease adequately.

Objective: To assess the degree of correlation between the asthma control perceptions by patients and by physicians.

Methods: Observational, cross-sectional and multicenter study that included patients with severe persistent asthma according to Spanish Guidelines for Asthma Management (GEMA). We calculated the degree of agreement between asthma control perceptions by patients, physicians and according to the GEMA.

Results: A total of 343 patients were included. Mean age (SD) was 48.1 (14.7) years and 1/3 were women. The assessment of the degree of asthma control according to GEMA criteria showed that only 10.2% of patients were controlled, 27.7% partially controlled and 62.1% poorly controlled. The correlation between patient's asthma control perception and according to GEMA criteria showed that 35.7% of patients that viewed themselves under control did not achieve GEMA criteria (p<0.0001). The agreement between physicians and GEMA criteria showed that 16.6% of asthma patients who reached medical criteria for control, were not under the GEMA control assumptions (p<0.0001). Concordance between medical criteria and patient's perception showed that only 57.9% of cases coincided for the control of asthma, while 40.7% of patients who felt controlled were not under physician opinion (p<0.0001).

Conclusions: Both patients and physicians overestimate asthma control, with higher control perception in patients.
Combined Treatments With Vitamin A and 5-Fluorouracil and the Growth of Allotransplantable and Syngeneic Tumors in Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Y Tomita, K Himeno, K Nomoto, H Endo, T Hirohata
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Combined Treatments With Vitamin A and 5-Fluorouracil and the Growth of Allotransplantable and Syngeneic Tumors in Mice, Get access Voshifumi Tomita, Voshifumi Tomita Search for other works by this author on: Oxford Academic PubMed Google Scholar Kunisuke Himeno, Kunisuke Himeno Search for other works by this author on: Oxford Academic PubMed Google Scholar Kikuo Nomoto, Kikuo Nomoto Search for other works by this author on: Oxford Academic PubMed Google Scholar Hideya Endo, Hideya Endo Search for other works by this author on: Oxford Academic PubMed Google Scholar Tomio Hirohata Tomio Hirohata Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 68, Issue 5, May 1982, Pages 823–827, https://doi.org/10.1093/jnci/68.5.823 Published: 01 May 1982 Article history Received: 14 July 1981 Accepted: 15 December 1981 Published: 01 May 1982
Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia
Authors: Yoseph C. Elala, Terra L. Lasho, Naseema Gangat, Christy Finke, Daniela Barraco, Mahnur Haider, Ahmed K. Abou Hussein, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: American Journal of Hematology (2016)

About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ∼15%) are wild type for all three mutations and are referred to as being "triple negative." Furthermore, CALR mutations in ET are structurally classified as type 1/type 1-like or type 2/type 2-like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis-free (MFFS), thrombosis-free, and leukemia-free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple-negative. Among the 109 CALR-mutated cases, 52% were classified as type 1/type 1-like and 48% as type 2/type 2-like. In univariate analysis, triple-negative patients displayed the best and MPL mutated the worst OS (P = 0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P = 0.5). LFS was also similar among the different mutational groups (P = 0.6) whereas MFFS was significantly shorter in MPL-mutated patients on both univariate and multivariable analyses (age-adjusted P = 0.02; HR 7.9, 95% CI 2.0-31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P = 0.02; HR 1.9, 95% CI 1.1-3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis.
Effect of the immune modulating peptide, SCV-07, in the murine B16 melanoma model
Authors: C. W. Tuthill, Y. Liu, Q. Cai, H. Wang, A. Kung
Journal: Journal of Clinical Oncology (2007)

13514 Background: SCV-07 (gamma-D-glutamyl-L-tryptophan) is a synthetic peptide with proven immune stimulating effects and efficacy against various viral and bacterial infections. As several cancers, including melanoma, are known to be sensitive to immune modulation, it was of interest to evaluate the effects of this compound in the murine B16 melanoma model. Methods: Tumors (1x10 6 B16 melanoma cells) were implanted subcutaneously (sc) into the right axillary area of C57BL/6 mice (Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, P. R. China). SCV-07 was dissolved in phosphate buffered saline (PBS) and administered once daily via sc administration (at a different site from tumor implantation) at doses of 0.01, 0.10, 1.0, or 5.0 mg/kg for 14 consecutive days. Positive control, dacarbazine (DTIC) was given at a dose of 50 mg/kg once daily for 14 consecutive days via sc injection. Tumor size (by caliper) and body weights were measured once every 3 days throughout the study. The study was terminated on day 17, and the animals euthanized. The tumors were excised, separated, and weighed. Results: SCV-07 treatment led to a significant inhibition of tumor growth compared to vehicle control, with decreases of 16.5% (p=0.030) and 30.2% (p=0.014) seen at the highest doses of 1.0 and 5.0 mg/kg, respectively, on day 15 at the end of treatment. Growth inhibition in the DTIC control was 95.1% (p&lt;0.001). Evaluation of tumor weight also demonstrated a significant inhibition by SCV-07, compared to vehicle, of 23.5% (p=0.008) and 30.8% (p=0.015) at dose levels of 1.0 and 5.0 mg/kg SCV-07. DTIC treated animals had a decrease in tumor weight of 85%. Evaluation of animal body weights demonstrated a significant decrease in those treated with DTIC, suggesting a toxic effect, while no decrease was noted in any SCV-07 treatment groups. Conclusions: Administration of SCV-07 once daily for 14 consecutive days via the sc route is effective against B16 melanoma tumor growth. Tumor growth in animals treated with dose levels of 1 or 5 mg/kg of SCV-07 was significantly reduced compared to the vehicle control group. The overall animal body weights were unchanged after treatment with SCV-07, indicating a lack of toxicity of the test article. No significant financial relationships to disclose.
A feasibility study of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in patients with epithelial ovarian carcinoma, fallopian tube carcinoma, or peritoneal carcinoma
Authors: S. Nagao, R. Oishi, N. Iwasa, M. Shimizu, K. Hasegawa, T. Goto, K. Fujiwara
Journal: Journal of Clinical Oncology (2009)

e16549 Background: This is a feasibility study for a future trial to assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin and IP paclitaxel (TCipTip therapy) in patients with epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma. Methods: The patients eligible for this study had histologically confirmed, stage IC-IV epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma. IV paclitaxel was administered at 135 mg/m 2 followed by IP carboplatin administration based on the area under the curve =6 on day1, and IP paclitaxel was administered at 60 mg/m 2 on day 8. To ensure the safety, the three initial patients received 45 mg/m 2 of IP paclitaxel on day 8. The toxicity grade was determined by CTCAE version 3. This study has been approved by the institutional review committee. Results: During November 2007 and December 2008, 10 patients were entered in this study. The patients included 7 epithelial ovarian carcinoma (stage IC, 2; stage IIIC, 5), 2 stage IIIC primary peritoneal carcinoma, and 1 stage IIA fallopian tube carcinoma. There were 7 serous adenocarcinoma, 2 endometrioid adenocarcinoma, 1 clear cell adenocarcinoma. The incidences of grade 3/4 hematological toxicities were 48% for neutropenia, 28% for thrombocytopenia, and 48% for anemia. Grade 3/4 neurotoxicity, abdominal pain nor IP catheter related toxicity was not observed. IP paclitaxel at 2 nd or 3 rd cycle was skipped in 4 patients by grade 3/4 neutropenia (grade 3, 3; grade 4, 1 ). Conclusions: TCipTip therapy is feasible for patients with epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma. No significant financial relationships to disclose.
Phase II clinical trial of low-dose interleukin-2, interferon-alpha, and low-dose tegafur uracil therapy for advanced renal cell cancer.
Authors: Tomoyuki Kato, Masatsugu Iwamura, Tetsuo Fujita, Seiichi Saito, Yoshinori Ohshiro, Tomoyuki Imai, Nozomu Kawata, Yoshihiko Tomita, Takehiro Sejima, Takeshi Kishida, Tatsuo Tochigi, Sadafumi Kawamura
Journal: Journal of Clinical Oncology (2015)

508 Background: The objective of this trial was to evaluate the efficacy and safety of immunochemotherapy with very low-dose interleukin-2, interferon-alpha and tegafur uracil (IAT therapy) in treatment naïve metastatic renal cell carcinoma (RCC) patients with pulmonary metastasis only. Methods: Previously untreated metastatic renal cell cancer patients only with pulmonary metastasis were enrolled in this multicenter, open-label, single arm, phase II trial. Eligibility criteria included ECOG performance status (PS) 0-2, low or intermediate risk per MSKCC score, and adequate organ function. The primary endpoint was the overall response rate (ORR) per RECIST v1.1. Secondary endpoints were time to progression (TTP), response duration, overall survival (OS), ECOGPS and safety. Safety was assessed by CTCAE, v4.0. Low dose (0.7-2.1 MIU/ day) IL-2 was administered intravenously in the first five days of the first and third week. IFN-alpha (500 MIU/day) was administered 3 times per week in week 2. From 4th to 7th weeks, patients received IFN- alpha 3 times per week and 100 mg tegafur uracil t.i.d. Results: Twenty-eight eligible patients were enrolled from Apr 2009 through Dec 2013. Twenty-one patients were evaluable for ORR. Three patients had partial response (PR) 11 stable disease (SD), and 7 progressive disease (PD). ORR was 14.4% and median duration of PR was 18.0 months. TTP and OS were not reached to median and 3-year OS rate was 76.3%. Twenty-seven patients (96.4%) had an ECOGPS of 0 and 1 (3.6%) had PS of 1. Three patients experienced exacerbation in PS (PS 0 to 1). The most common adverse events (AEs) were elevation of ALT (35.7%) and fever (32.1%). AEs grade 3 included rash (14.3%), depression (3.2%), syncope (3.2%), fever (3.2%), elevation of ALT (3.2%). Four patients discontinued therapy at the time of ORR analysis due to AEs (3 rash, 1 depression). Conclusions: IAT therapy for RCC patients with only pulmonary metastasis is safe and appears to have clinical benefit as reflected by ORR rate and long OS. Clinical trial information: 00002222.
Definitive chemo-radiotherapy (CRT) with folfox 4 or 5FU-cisplatin as first line treatment for patients (pts) with inoperable esophageal cancer (IEC): Final results of a randomized phase II study
Authors: T. Conroy, Y. Yataghene, P. L. Etienne, P. Michel, H. Senellart, J. L. Raoul, L. Mineur, M. Rives, X. Mirabel, A. Adenis
Journal: Journal of Clinical Oncology (2007)

4532 Background: The RTOG regimen of concurrent CRT with 5FU/CDDP represents the standard treatment of pts with IEC (Al- Sarraf JCO, 1997). As new combinations are required to improve survival, we launched a multicenter randomized phase II study to assess the feasibility and endoscopic complete response rate (ECRR) of combination CRT with Folfox 4 (arm A) or 5FU/CDDP (arm B) in pts with IEC. Methods: Radiotherapy (RT) was in both arms 50 Gy (2Gy/fraction) 5 days/ week for 5 weeks. In Arm A, pts received 6 biweekly cycles (cy): Oxaliplatin 85mg/m2 d1 and Leucovorin 200mg/m2 followed by 5-FU 400mg/m2 bolus and 600mg/m2 22h continuous infusion (C.I.) d1–2 ; the first 3 cy were delivered during RT, the 3 other after. Arm B: 4 cy were delivered: CDDP 75mg/m2 d1 followed by 5FU 1,000 mg/m2/d C.I. d1–4, the first two cy during RT and 2 other after RT. To be evaluable pts must have completed the concurrent CRT. Response evaluation (esophagoscopy + CT-scan) was done on week 15; ECRR was reviewed by an independent expert committee. Results: 97 pts (A/B= 53/44) were included and 95 treated: 19% adenocarcinoma, 81% squamous cell carcinoma; median age 59 [39–81] and PS 0–1: 98%. In arms A/B, 89/91% of pts completed the concurrent CRT and 75/70% the full treatment. Main NCI-CTC grade (G) 3–4 toxicities (% per pt) were in arms A/B: neutropenia 19/19, febrile neutropenia 12/5, neutropenic infection 2/7, esophagitis 8/14. Neurotoxicity: in arms A/B, 13%/ 2% of pts had G 2 and 46%/13% G 1 neuropathy, no G 3 neuropathy occurred. 47/40 pts (90%) were evaluable for response. In the ITT population, the ECRR was 44.7% and 30.0%, median TTP was 15.0 [9.9–18.9] / 9.5 [7.6- not reached (NR)] months (mos), median Event Free Survival was 11.6 [8.6–17.2]/ 7.8 [5.1–9.9] mos and the median overall survival was 22.7 [16.7-NR]/ 14.7 [9.2–17.2] mos, in arms A and B respectively. Conclusions: The new concurrent CRT with Folfox4 is a well tolerated and convenient combination with promising efficacy associated with very good survival results. Final data will be presented at the meeting. The study continues as a phase III trial. No significant financial relationships to disclose.