tbuckley/cabot-search huggingface dataset:
Abstract 5681: Flavokawain B down-regulates SKP2 through a proteasome-dependent and ubiquitin-independent pathway, and acts synergistically with Bortezomib on inhibition of Skp2 expression and prostate cancer cell growth
Authors: Xuesen Li, Zhongbo Liu, Anne R. Simoneau, Xiaolin Zi
Journal: Cancer Research (2010)

Abstract The E3 ubiquitin ligase SKP2 (S-phase kinase-associated protein 2), an oncogenic protein, was found to be overexpressed in 557 of 622 (89.2%) primary prostate cancer (PCa) samples and in 64 of 74 samples (86.4%) high-grade prostatic intra-epithelial neoplasia lesions. In addition, a transgenic mouse model with prostatic over-expression of SKP2 develops low-grade adenocarcinomas. These results suggest that SKP2 could be a potential target for PCa chemoprevention. In a search for SKP2 targeting agents for PCa chemoprevention, we found that Flavokawain B, a chalcone found in multiple edible plants- including roots of Alpinia speciosa (family Zingiberaceae) and Piper methysticum Forst (kava kava), potently down-regulates the protein expression of SKP2 in several prostate cancer cell lines (LNCaP, C4-2B, DU145 and PC3) at a concentration of 8.8 µM. More importantly, Flavokawain B reduces the cell viability of transfected PC3 cell line stably overexpressing SKP2 compared to vector control-transfected PC3 cells (IC50s are 7 and 26.4 µM, respectively), which suggest that flavokawain B may target SKP2 for its growth inhibitory effect. Flavokawain B treatment did not decrease the promoter activity and mRNA levels of SKP2. Instead, Flavokawain B decreases the protein levels of both a native and a myc-tagged SKP2 in PC3 cells through promoting its degradation. The degradation of the myc tagged SKP2 can be recovered by a proteasome inhibitor MG132. MG132 treatment resulted in an increase of ubquitinated SKP2, whereas Flavokawain B did not affect SKP2 ubquitination. These data suggest that the degradation of SKP2 by Flavokawain B may be through a proteasome-dependent and ubquitination-independent pathway. Interestingly, proteasome inhibitors (MG132 and Bortezomib) also down-regulate SKP2 mRNA expression through transcriptional inhibition, and combination of Bortezomib or MG132 with Flavokawain B exhibits a synergistic effect on SKP2 down-regulation and cell growth inhibition via induction of G2M arrest in PCa cell lines. Taken together, Flavokawain B is a novel SKP2 target agent and deserves further investigation for PCa chemoprevention and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5681.
IMPELLA 2.5L COMPARED TO INTRAORTIC BALLOON PUMP IN PATIENTS WITH CARDIOGENIC SHOCK: A META-ANALYSIS OF STUDIES
Authors: Jad Omran, Tariq Enezate, Sudarshan Balla, Sirisha Vadali, Belal Firwana, Kul Aggarwal, Martin Alpert
Journal: Journal of the American College of Cardiology (2016)
AB0359 Doctor/patient match in disease evaluation activity in rheumatoid arthritis
Authors: S. Cadart, L. kanagaratnam, J. corli, R.-M. flipo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The evaluation of the activity of rheumatoid arthritis (RA) is essential in order to adapt the treatment. But, what is in real life the patient's opinion on activity of his disease? <h3>Methods</h3> The present study, single-center, cross-sectional, has included RA meeting ACR 1987 or EULAR 2010 criteria. The main of this study was to assess the correlation between physician composite index (DAS VS, DAS CRP, SDAI and CDAI) and the perceived level of disease activity by the patient himself. The secondary goal was to identify doctor/patient discrepancy factors. To do this, each patient completed a Beck evaluation form (to detect depression) and a HAQ evaluation form. <h3>Results</h3> This study included 162 patients, 56 years old (+/-13 years) on average, with 78% of women, followed in day hospital (48%) or in out-visit (52%), with a disease duration of 17 years (+/- 11). Rheumatoid factor was present among 85% of patients, anti CCPamong 81% of them and erosive disease among 80% of them. The average index were: 3.06 (+/-1.37) for DAS VS, 2.93 (+/-1.12) for DAS CRP; CDAI 10.8 (+/-9.6) and SDAI 17.6 (+/-15.4). Moderate activity level had the largest number of patients (31-37% depending on the index). Patients felt in remission (9%), in low activity (27%), in moderate activity (51%) and high activity (13%). Match was assessed by weighted kappa (k), with a poor doctor/patient correlation with DAS CRP (k = 0.21), SDAI (k = 0.38), CDAI (k = 0.39) and even worse with the DAS VS (k = 0.18). There were 64% of mismatch with the DAS VS. Univariate analysis showed that VAS pain and ESRwere significant mismatch factors, as well as treatments: abatacept and tocilizumab. The pain in the feet / forefeet, underlying depression and HAQ were not significant mismatch factors (p&gt; 0.2). Other variables included in the multivariate analysis models (0.05 &lt;p &lt;0.2) were VASactivity, painful and swollen joint count, the taking of corticotherapy, adalimumab and rituximab. Significant variables in multivariate were: adalimumab, abatacept, tocilizumab, inflammatory syndrome with ESR&gt; 20 mm VAS pain. <h3>Conclusions</h3> Doctor/patient match on the appraisal of disease activity is bad or poor, with 64% of mismatch VAS pain and VS are significant mismatch factors. <h3>Disclosure of Interest</h3> None Declared
Gastrojejunal anastomosis using a tissue-apposing stent: a safety and feasibility study in live pigs
Authors: Geoffroy Vanbiervliet, Eduardo Bonin, Rodrigo Garcès, Jean-Michel Gonzalez, Emmanuelle Garnier, Marie Paul, Stéphane Berdah, Marc Barthet
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Various techniques using surgical and natural orifice transluminal endoscopic surgery (NOTES) have been evaluated to create a gastrojejunal bypass. The aim of the current study was to determine the safety, feasibility, and efficacy of a new technique using a pure endoscopic approach and tissue-apposing stent placement for gastrojejunal anastomosis (GJA). <b>Materials and methods: </b>This was a prospective, experimental study on six live pigs weighing 20 – 45 kg. Endoscopies were performed using a double-channel gastroscope, and included the creation of a GJA using a tissue-apposing, fully covered, self-expanding metallic stent. Antibiotic therapy was continued for 7 days after the procedure, and food was gradually reintroduced from Day 3. Changes in weight following the procedure were compared with a control group of age-matched animals. Anastomosis functionality was confirmed by endoscopy at 3 weeks (before the animals were euthanized), and during histopathological analysis. The primary outcomes were morbidity and mortality at 3 weeks. Secondary outcomes were technical feasibility, procedure time, and patency of the GJA. <b>Results:</b> The procedures were performed successfully in all animals. The mean procedure time was 26 ± 6.7 minutes (range 15 – 32 minutes). One case of stent migration occurred during the procedure; the stent was successfully replaced using the same procedure. All animals were alive after 3 weeks. The mean weight gain during follow-up was 0.85 ± 2.56 kg (range – 2 to + 2 kg) compared with 5.2 ± 1.6 kg (range 3 – 7 kg) in control animals (<i>P</i> = 0.007). At necropsy, the stents were still in place in all animals, without evidence of peritonitis. Histopathology confirmed permeable anastomoses with continuity of the mucosa and mucosa muscle layers. <b>Conclusions: </b>GJA with a tissue-apposing stent is safe, feasible, and reproducible without anastomotic leakage in a porcine model using a pure endoscopic approach and standard endoscopic equipment.
Abstract P080: Associations of Poor Sleep Quality and Quantity and Subclinical Atherosclerosis in Older Age - The Chicago Healthy Aging Study (CHAS)
Authors: Thanh Huyen T Vu, Norrina B Allen, Kathryn J Reid, Kiang Liu, Daniel B Garside, Martha L Daviglus, Phyllis C Zee
Journal: Circulation (2013)

Background: Previous studies have demonstrated a link between both sleep quantity and quality and an increased risk of CVD, stroke, and diabetes. However only a few population-based studies have information on the association of sleep quantity and quality and subclinical atherosclerosis as measured by coronary artery calcium (CAC) and ankle brachial index (ABI) -- a marker for peripheral arterial disease. Methods: CHAS data were used to investigate cross-sectional associations of short sleep duration and poor sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) (see Table Footnote for definition of poor sleep quality and quantity) and prevalence of having CAC (score &gt; 0) or low ABI (&lt;0.99). CAC, assessed by multi-detector computed tomography, was quantified by the Agatston’s method. ABI was calculated as the ratio of Doppler recorded systolic pressures in the lower and upper extremities (ABI &gt;1.4 was excluded). Results: The study sample consists of 1,005 men and 390 women ages 65-84 (mean age 71) in 2007-10; 9% were African American. There are no differences in CAC prevalence among participants with or without short sleep duration (11.2% vs. 11.0%). For low ABI, these figures are 20% and10.8%, respectively. With multiple adjustments (see Table Footnote), there are no significant associations of short sleep duration or poor sleep total score with prevalent CAC. However, participants with short sleep duration are more likely to have low ABI, i.e., the odds (95% confidence interval) of having ABI &lt;0.99 with sleep duration of &lt;6hrs was almost two fold (1.02-3.13) compared to others (see Table). Conclusion: In older age, shorter sleep duration is associated with peripheral vascular disease. Sleep may represent a modifiable risk factor for CVD.
Abstract 1632: Novel naproxen, resveratrol and sulforaphane (NRS) combinations demonstrate synergistic decrease in cell viability of human colon and pancreatic cancer cell lines
Authors: B. Karthik Grandhi, Arvind Thakkar, Sunil Prabhu
Journal: Cancer Research (2012)

Abstract Gastrointestinal cancers, in particular colon and pancreatic cancer, account for almost 100,000 deaths each year in the United States, ranking third and fourth respectively, in the most common cause of cancer related deaths. Our lab has been focused on developing strategies for chemoprevention rather than treatment after diagnosis. For pancreatic cancer, the prognosis is usually poor with high mortality rates after diagnosis. Thus, the objective of this work was to study the effects of chemopreventive combination regimens of a non-steroidal anti-inflammatory drug (NSAID) naproxen (N), in combination with resveratrol (R, an antioxidant) and sulforaphane (S, a broccoli extract) on human colon (HT-29 and HCT-116) and pancreatic (MIA PaCa-2 and Panc-1) cancer cell lines. MTS cell proliferation assay was conducted on all cell lines. For the MTS assay, upon 75 % confluence, 100µL of 2.5X103 cells each of HT-29, HCT116 and MIA PaCa-2 and 4X10 3 cells Panc-1 cells were transferred into each well of 96-well plates. The NRS chemopreventive agents alone, or in combination, were added to the cells and incubated for 72 h. The plates were then incubated for 1-4 h at 37°C in a humidified, 5% CO2 atmosphere. Absorbance was recorded at 490 nm using an ELISA plate reader. For HT-29 and HCT 116 colon cancer cell lines, the combinations of naproxen (500µM/L) with resveratrol (50µM/L) and sulforaphane (5µM/L) showed reduction in cell viability of 56.74% and 52.9%, respectively. The IC50 values for NRS were 1.46 mM/L,104.54µM/L and 17.81µM/L respectively on HT-29 cell line. Similarly, for MIA PaCa-2 and Panc-1 pancreatic cancer cell lines, combinations of naproxen (500µM/L) with resveratrol (6µM/L) and sulforaphane (5µM/L) showed reduction in cell viability of 66.67% and 58.8% respectively. The IC50 values for NRS were 778µM/L, 74.8µM/L and 11.82µM/L respectively, on MIA Paca-2 cell line. When used individually, none of the chemopreventive agents at the above concentrations demonstrated any decrease in cell viability, however when combined together, a synergistic effect was observed. Our results demonstrate that NRS drug combinations at low concentrations exhibit significant decrease in cell proliferation in both human colon and pancreatic cancer cell lines. This data provides compelling evidence of the potential of these combination regimens for the chemoprevention of colon and pancreatic cancer. 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 1632. doi:1538-7445.AM2012-1632
P17.55 * UNRAVELLING GRADE 3 GLIOMAS
Authors: R. Mathew, E. Goacher, D. Bhargava, A. Chakrabarty, P. Roberts, J. Goodden, C. Loughrey, P. Chumas
Journal: Neuro-Oncology (2014)

INTRODUCTION: Patients diagnosed with WHO Grade III Gliomas experience huge variations in overall survival and treatment response. In general, Grade II and Grade IV gliomas behave more predictably. We have attempted to identify factors within grade III gliomas that may better inform clinicians about the prognosis of this heterogeneous group of tumours. METHODS: Retrospective (1988-2013) case note, database, cytogenetic and tissue sample review of patients histologically diagnosed with WHO Grade III Gliomas. Demographics, molecular data (1p19q co-deletion, IDH mutation, Ki67/MIB), percentage of Grade II features and overall survival (OS) was analysed. Mortality was defined as any cause of death within 12, 18, 24, 36, 48 and 60 months of diagnosis. Results were statistically analysed by Kaplan-Meier and Log Rank (Cox Proportional Regression Hazard) Testing (p < 0.05). RESULTS: Patients (n = 158) had a mean age of 46 years (range 6 days-77 years) with 54% male and 46% female. Mean OS was 25.2 months (range 0-125 months). Diagnoses were 78.5% astrocytoma, 9.5% oligoastrocytoma, 10.1% oligodendroglioma and 1.9% other. Debulking (versus biopsy), adjuvant therapy, age <50 years, 1p19q co-deletion, and intermediate proliferation rate (10-20%) significantly improved OS. Late OS (>48 months) was better for females. Tissue analysis for percentage Grade II features is ongoing. CONCLUSION: Debulking surgery, adjuvant therapy and age are well-established prognostic indicators. Molecular factors are possibly more weighted factors in predicting tumour behaviour and outcome. Routine availability of molecular genetics and the percentage of Grade II features will likely redefine this group of tumours into subcategories.
Abstract 4082: Protection of acetaminophen-induced cytotoxicity by diallyl sulfide in mouse macrophages and HepG2 cells
Authors: Haider Raza, Annie John
Journal: Cancer Research (2011)

Abstract The nonsteroidal anti-inflammatory drugs (NSAIDs), including acetaminophen (APAP), have been reported to induce cytotoxicity in cancer and non-cancerous cells. The precise molecular mechanisms, however, are not well understood. Our previous studies on HepG2 cells treated with aspirin and mouse macrophage J774.2 cells treated with APAP strongly suggest cell cycle arrest and induction of apoptosis associated with mitochondrial dysfunction and oxidative stress. Macrophages are known to play a critical role in toxicity as well as in protection of target tissues against the toxicity induced by NSAIDs. In the present study, we have demonstrated that macrophages are a more sensitive target for APAP -induced toxicity than HepG2 cells. Using similar dose- and time-point studies, a marked increase in apoptosis, DNA fragmentation, cytochrome c release and PARP/caspase 3 activation was seen in macrophages compared to HepG2 cells. Differential effects of APAP on mitochondrial respiratory functions and oxidative stress were observed in the two cell lines which are presumably dependent on the varying degree of reactive oxygen species (ROS) production and alterations in glutathione metabolism. In contrast to macrophages, our results also demonstrate a marked increase in glutathione transferase activity in APAP-treated HepG2 cells. This may explain the apparent resistance of HepG2 cells to APAP toxicity compared to the macrophages. Treatment of these cells with diallyl sulfide (DAS, 200 µmol/ml), a known chemopreventive agent from garlic extract, 24 h prior to APAP (10 µmol/ml for 18h) exposure have also exhibited comparable cytoprotective effects in the two cell lines. These results may help in better understanding the mechanism of cytotoxicity caused by APAP and cytoprotection by chemopreventive agents in cancer and non-cancerous cellular systems. (Supported by Terry Fox Cancer Research Funds and a fund from FMHS Research Committee). 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 4082. doi:10.1158/1538-7445.AM2011-4082
AB0352 Vaccination against hepatitis B in patients with psoriatic arthritis (PA). Preliminary results with double dose schedule
Authors: A. De Juanes, M.P. Arrazola, A. García de Codes, R. González Crespo, P. Gil, I. Mateo, J.R. de Juanes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The different drug treatments in rheumatic patients can lead to situations of immunosuppression and predispose to infection by immunization. <h3>Objectives</h3> To present preliminary results of antibody response of immunisation with a double-doses recombinant hepatitis B vaccine and its effectiveness in these patients. <h3>Methods</h3> Of the 532 adult patients referred by the Department of Rheumatology at the Immunization Unit of Preventive Medicine of this hospital to assess their vaccination status from the beginning of the protocol in January 2010, 55 correspond to diagnoses of PA. We have studied the variables of sex, treatment with corticosteroids (yes/no), and other treatments such as methotrexate, anti-TNF monotherapy, MTX and anti-TNF. Patients in whom vaccination was indicated (negative antibody level against HBsAg) were vaccinated with a double dose. <h3>Results</h3> Of the patients diagnosed with PA (55), 12 were not vaccinated (background infection, previously vaccinated, elderly, etc.). Of the remaining 43, 1 left the vaccination and 10 were pending completion of the vaccination schedule. Of the remaining 32, 6 were pending serological testing postvaccination. 26 patients completed vaccination and postvaccination control anti-HBs. Of these 22 (84.6%) patients we given a double-dose schedule. 9 (39%) of them presented a positive control and 13 post-vaccination negative serology. Among patients with positive results, 4 were women and 5 were men. Of the 9 patients with positive results, 7 (77.7%) were not administered corticosteroids. Of the13 patients with negative serology, 77.0% were not administered corticosteroids. Of the 9 patients with positive results, only 3 were treated with MTX. Of the 6 patients treated with anti-TNF, 4 were positive in the post-vaccination control. In 2 patients treated with MTX and anti-TNF postvaccination the control was positive. No significant adverse effects have been detected and no exacerbation of their disease <h3>Conclusions</h3> 39% of postvaccination patients screened serologically were positive. Of the patients with positive results, 77.7% were not administered corticosteroids. We understand the need to increase vaccination policies from the time of their diagnosis before the patients begin with immunosupressive treatment. <h3>References</h3> Beck CR, McKenzie BC, Hashim AB, Harris RC, Zanuzdana A, Agboado G, et al. Influenza Vaccination for Immunocompromised Patients: Systematic Review and Meta-Analysis from a Public Health Policy Perspective PloS One 2011; 6(12). E29249. <h3>Disclosure of Interest</h3> None Declared
IL6 Blockade Reprograms the Lung Tumor Microenvironment to Limit the Development and Progression of K-ras–Mutant Lung Cancer
Authors: Mauricio S. Caetano, Huiyuan Zhang, Amber M. Cumpian, Lei Gong, Nese Unver, Edwin J. Ostrin, Soudabeh Daliri, Seon Hee Chang, Cesar E. Ochoa, Samir Hanash, Carmen Behrens, Ignacio I. Wistuba, Cinthya Sternberg, Humam Kadara, Carlos Gil Ferreira, Stephanie S. Watowich, Seyed Javad Moghaddam
Journal: Cancer Research (2016)

Abstract Activating mutations of K-ras are the most common oncogenic alterations found in lung cancer. Unfortunately, attempts to target K-ras–mutant lung tumors have thus far failed, clearly indicating the need for new approaches in patients with this molecular profile. We have previously shown NF-κB activation, release of IL6, and activation of its responsive transcription factor STAT3 in K-ras–mutant lung tumors, which was further amplified by the tumor-enhancing effect of chronic obstructive pulmonary disease (COPD)-type airway inflammation. These findings suggest an essential role for this inflammatory pathway in K-ras–mutant lung tumorigenesis and its enhancement by COPD. Therefore, here we blocked IL6 using a monoclonal anti-IL6 antibody in a K-ras–mutant mouse model of lung cancer in the absence or presence of COPD-type airway inflammation. IL6 blockade significantly inhibited lung cancer promotion, tumor cell–intrinsic STAT3 activation, tumor cell proliferation, and angiogenesis markers. Moreover, IL6 inhibition reduced expression of protumor type 2 molecules (arginase 1, Fizz 1, Mgl, and IDO), number of M2-type macrophages and granulocytic myeloid-derived suppressor cells, and protumor T-regulatory/Th17 cell responses. This was accompanied by increased expression of antitumor type 1 molecule (Nos2), and antitumor Th1/CD8 T-cell responses. Our study demonstrates that IL6 blockade not only has direct intrinsic inhibitory effect on tumor cells, but also reeducates the lung microenvironment toward an antitumor phenotype by altering the relative proportion between protumor and antitumor immune cells. This information introduces IL6 as a potential druggable target for prevention and treatment of K-ras–mutant lung tumors. Cancer Res; 76(11); 3189–99. ©2016 AACR.
The Dangers of Modern Insulin Syringes
Authors: William S. Collens, Louis C. Boas, James D. Zilinsky
Journal: New England Journal of Medicine (1946)

SINCE the discovery of insulin, a situation has existed in connection with the syringe employed for its administration that has never been satisfactory. The original introduction of a variety of insulin concentrations necessitated the construction of hypodermic syringes with different calibrations corresponding to these various concentrations. Apparently, in an attempt at economy, syringes with double graduations were manufactured. Thus, to provide syringes for the injection of insulins of U 10, U 20, U 40 and U 80 strengths, the manufacturer supplied a U 10–20 syringe, — used for U 10 and U 20 insulin, — a U 20–40 syringe —used . . .
Stat Bite Cancer Drugs in Development
Authors: M. Grayson
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Stat Bite Cancer Drugs in Development Get access Mark Grayson Mark Grayson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 11, 1 June 1994, Page 823, https://doi.org/10.1093/jnci/86.11.823 Published: 01 June 1994