tbuckley/cabot-search huggingface dataset:
Abstract 863: Tyrosine kinase activity profiling of metastatic malignant melanoma: Identification of possible therapeutic targets and markers predicting response to therapy
Authors: Andliena Tahiri, Kathrine Roe, Christian Busch, Per Eystein Lonning, Anne H. Ree, Vessela N. Kristensen, Juergen Geisler
Journal: Cancer Research (2012)

Abstract Metastatic melanoma is an aggressive form of skin cancer that is highly resistant to conventional chemotherapy. Thus, novel approaches to improve the current treatment of advanced melanoma are urgently needed. Kinases are key regulators of cellular processes, and since nearly half of the tyrosine kinase complement is implicated in cancer, the information of kinase activity in tumors give important tumor-specific information on affected pathways and potential targets for treatment. With this in mind, we performed tyrosine kinase activity profiling of 26 tissue samples obtained from patients suffering from metastatic stage IV melanoma, prior to dacarbazine (DTIC) treatment, using Tyrosine Kinase PamChip® microarrays. Each sample lysate generated an individual phospho-substrate signature, representing the state of the kinase signalling cascades, which allowed us to compare affected targets in responders and non-responders to DTIC treatment. Further, we attempted to evaluate the kinase activity in response to BRAF inhibitor, PLX4032 (Vemurafenib), which has shown dramatic and positive effects in advanced melanoma tumors, and has recently been approved for the treatment of late stage melanoma. In this case, incubation was carried out on all samples with and without PLX4032. Our preliminary results showed that although the compound is mainly directed against a serine/threonine kinase, BRAF, PLX4032 also showed inhibitory effects on the activity of multiple tyrosine kinases. Since the drug is only beneficial for melanoma patients with BRAF V600E mutations, we compared the activated kinase pathways in patients with and without this mutation in order to identify alternative survival pathways in patients with wild type BRAF. The technology used in this study is based on a unique 3D flow-through microarray format that allows monitoring of the reaction in real time, ideal for the characterization of pathways. Each array contained 144 peptide substrates with sites for phosphorylation, representing about 100 different proteins. The use of kinase inhibitors will cause inhibition of corresponding kinases of activated signalling pathways; hence, providing us leads to therapeutic targets and possible prediction markers for response to therapy. The detailed effects of both PLX4032 and sunitinib in the chosen test system are currently prepared for presentation. 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 863. doi:1538-7445.AM2012-863
Newly developed flexible endoscopic scissors for removal of a nasogastric tube trapped within a gastrojejunal anastomotic staple line
Authors: M. Wilkinson, V. Jayaraman, K. Watkins, P. Bao, J. Buscaglia
Journal: Endoscopy (2011)

A 72-year-old woman underwent a laparorobotic pancreaticoduodenectomy using the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, California, USA) for removal of a 4-cm ampullary adenoma. Intraoperatively, a nasogastric tube was inserted into the gastric fundus and its proximal end was secured to the patient’s nares. On postoperative day 2, the tube could not be removed at the bedside.
P499 ALTERED GUT MICROBIOME IS ASSOCIATED WITH NEURO-INFLAMMATION ON BRAIN MRI IN CIRRHOSIS: IMPLICATIONS FOR THE GUT–LIVER–BRAIN AXIS
Authors: J.S. Bajaj, V.S. Ahluwalia, M. Sikaroodi, J. Wade, M. White, D. Heuman, H. Gilles, A. Unser, P. Hylemon, P.M. Gillevet
Journal: Journal of Hepatology (2014)
1309 miR-451 INHIBITS FATTY ACID-INDUCED INCREASES IN NF-κB TRANSACTIVATION THROUGH AMPK IN NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Authors: S.K. Yoon, W. Hur, Y.K. Lee, S.W. Kim, S.W. Hong, S.W. Choi, S.H. Cho, J.M. Yang, Y.S. Lee
Journal: Journal of Hepatology (2013)
Neurologic and Developmental Disability after Extremely Preterm Birth
Authors: Nicholas S. Wood, Neil Marlow, Kate Costeloe, Alan T. Gibson, Andrew R. Wilkinson
Journal: New England Journal of Medicine (2000)

Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria.At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability.Severe disability is common among children born as extremely preterm infants.
Abstract 1284: Combined genetic and nutritional risk models of triple negative breast cancer.
Authors: Jennifer J. Hu, Eunkyung M. Lee, Glenn O. Allen, Edward A. Levine
Journal: Cancer Research (2013)

Abstract Purpose: Triple negative breast cancer (TNBC), which lacks treatment targets for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), has been associated with African-American race, BRCA1/2 mutations, TP53 mutations, and poor prognosis. However, the etiology of TNBC remained unknown, which represents a critical barrier in reducing breast cancer mortality. Therefore, we designed a case-only study to test combined genetic and nutritional risk models of TNBC. Methods: In 354 breast cancer patients diagnosed between 1998 and 2004, we evaluated 18 DNA-repair non-synonymous single nucleotide polymorphisms (nsSNPs) using the Sequenom MassARRAY system. The 110-item Block 1998 food frequency questionnaire was used to evaluate dietary/nutritional intakes. The Multivariate Adaptive Regression Splines (MARS)-logit models were used to define nutritional intakes cut-offs for their associations with TNBC. Results: TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or 3 micronutrients (zinc, folate, and β-carotene). Combined DNA-repair risk genotypes and lower micronutrient intakes had a significant dosage-dependent association with TNBC (p&amp;lt;0.001): ORs=2.77 (95%CI=1.01-7.64), 9.57 (95%CI=2.87-31.84), and 20.78 (95%CI=2.46-175.71) for 2, 3, and at least 4 risk factors, respectively. Conclusion: To the best of our knowledge, this is the first study to demonstrate multiple DNA repair SNPs and nutritional factors are associated with TNBC. Our results suggest that dietary modulation and micronutrient supplementation may have implication in preventing or reversing TNBC, particularly in genetically susceptible women. Citation Format: Jennifer J. Hu, Eunkyung M. Lee, Glenn O. Allen, Edward A. Levine. Combined genetic and nutritional risk models of triple negative breast cancer. [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 1284. doi:10.1158/1538-7445.AM2013-1284
P5-13-14: Drug-Metabolizing Enzyme Polymorphisms and Clinical Outcome of Anthracycline-Based Chemotherapy in Chinese Han Breast Cancer Patients.
Authors: J Tang, J Zhao, J Wu, M Ji, S Zhong
Journal: Cancer Research (2011)

Abstract Background Anthracycline is one of the most effective drugs in the treatment of breast cancer and many of our most effective treatment regimens include anthracycline. Its efficacy can be influenced by cellular detoxification mechanisms involving drug metabolism and transport pathways. This study aimed to assess whether the functional polymorphisms in drug-metabolizing enzymes (MnSOD, CAT and GSTs) and transporter MDR1 may predict anthracycline treatment-related outcomes in Chinese Han breast cancer patients. Material and methods: Genotyping was performed by allele-specific oligonucleotide ligation reaction (MnSOD T47C, CAT C-262T, GSTP1 A313G), multiplex PCR (GSTM1 null, GSTT1 null), and PCR-RFLP (MDR1 C3435T, G2677T/A and C1236T). Based on 153 evaluable patients received anthracycline-based neoadjuvant chemotherapy for breast cancer, the associations of these genotypes or their haplotypes with clinical response and recurrence-free survival (RFS) were analyzed. Results: Of the 153 cases, the patients with GSTP1 313AA genotype had inferior response rates relative to those with AG or GG genotype (58.4% vs 77.8% or 100.0%; χ2=4.922, P=0.027). Moreover, the response rate of the combination of GSTP1 AA with both GSTT1 present and GSTM1 present was 44%, which was also lower comparing with the other groups (70.3%; χ2=6.454, P=0.011). A similar result was noticed for MDR1 3435 TT genotype, which had a significantly worse chemotherapy response compared with wild-type C allele carrier (33.3% vs 71.2%; χ2=11.586, P=0.001). Further, the response rate of the patients with 3435T-2677T, 3435T-1236T or 3435T-2677T-1236T haplotypes was lower than that of the patients with the other corresponding haplotypes (P=0.018, 0.011 and 0.019, respectively), too. Of note, the patients with both the adverse genotypes of GSTP1 314AA and MDR 3435TT shown the worst treatment efficacy in all (14.3%;χ2=26.33, P=0.000). Mean follow-up time of the 149 patients (4 patients lost) was 51 months. The recurrence rate in the patients with GSTP1 313AA or/and MDR 3435TT in the first three years was 39.0% (41/105), higher significantly than those with no adverse genotype [15.9% (7/44); OR=0.725, 95%Cl: 0.594−0.885, P=0.006]. Kaplan-Meier survival analysis showed that the patients with no adverse genotype were associated with reduced hazard of relapse (long-rank test, P&amp;lt;0.01), compared to those with 1 or 2 adverse genotypes. Conclusion: Polymorphisms in GSTs and MDR1 genes may help to predict clinical response and RFS of anthracycline-based chemotherapy in breast cancer, but further validation is required. These results provide support for a polygenic pathway approach for assessing the predictive potential of polymorphisms in treatment outcomes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-14.
PERFORMANCE OF AUTOMATIC QUANTITATIVE CORONARY PLAQUE ANALYSIS BY CT PLAQUE SUBTYPE: COMPARISON WITH INTRAVASCULAR ULTRASOUND
Authors: Hyung Bok Park, Ran Heo, Hyuk-Jae Chang, Reza Arsanjani, Sanghoon Shin, Sung Gyun Ahn, Byoung Kwon Lee, Myeong-Ki Hong, Yangsoo Jang, Namsik Chung
Journal: Journal of the American College of Cardiology (2015)
Contrast Nephrotoxicity: A Randomized Controlled Trial of a Nonionic and an Ionic Radiographic Contrast Agent
Authors: Steve J. Schwab, Mark A. Hlatky, Karen S. Pieper, Charles J. Davidson, Kenneth G. Morris, Thomas N. Skelton, Thomas M. Bashore
Journal: New England Journal of Medicine (1989)

Experimental studies have suggested that nonionic contrast agents are less nephrotoxic than ionic contrast agents. To examine the relative nephrotoxicity of the two types of agents, we randomly assigned 443 patients to receive either iopamidol (nonionic) or diatrizoate (ionic) for cardiac catheterization. The patients were stratified into low-risk (n = 283) or high-risk (n = 160) groups, on the basis of the presence of diabetes mellitus, heart failure, or preexisting renal insufficiency (base-line serum creatinine level, >133 μmol per liter). Serum and urine analyses were performed at base line and 24 and 48 hours after the infusion of contrast material. Nephrotoxicity was defined as an increase in the serum creatinine level within 48 hours of at least 44 μmol per liter. The median maximal rise in the serum creatinine level was 18 μmol per liter in both the diatrizoate group (n = 235) and the iopamidol group (n = 208) (P not significant; power to detect a difference >9 μmol per liter, >90 percent). Creatinine levels increased by at least 44 μmol per liter (0.5 mg per deciliter) in 10.2 percent of the patients receiving diatrizoate and 8.2 percent of the patients receiving iopamidol (P not significant). Among the high-risk patients, creatinine levels increased by at least 44 μmol per liter in 17 percent of the patients in the diatrizoate group, as compared with 15 percent of the patients in the iopamidol group (P not significant). We were unable to demonstrate a difference in the incidence of nephrotoxicity between patients receiving a nonionic contrast agent and those receiving an ionic contrast agent. (N Engl J Med 1989; 320:149–53.)
THE UTILITY OF NOVEL THREE-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY PARAMETERS FOR GLOBAL LEFT VENTRICULAR DYSFUNCTION ASSESSMENT: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY
Authors: Chike C. Nwabuo, Henrique T. Moreira, Henrique D. Vasconcellos, Guilherme Yared, Bharath Ambale Venkatesh, Satoru Kishi, Cora Lewis, Anderson Armstrong, Stephen Sidney, Donald Lloyd-Jones, Pamela Schreiner, Samuel Gidding, Joao Lima
Journal: Journal of the American College of Cardiology (2016)
Abstract 2645: PEITC induces cell death in melanoma cells through redox mechanisms
Authors: Kausar Begam Riaz Ahmed, Li Feng, Peng Huang
Journal: Cancer Research (2011)

Abstract Melanoma is one of the deadliest types of cancers accounting for about 80% of skin cancer deaths. Reactive oxygen species (ROS), produced by the mitochondrial respiratory chain and other biochemical mechanisms, play a critical role in melanoma progression through activation of transcription factors AP-1 and NF- κB and loss of E-cadherin. However, a further elevated level of ROS in cells, beyond a certain cellular threshold, may lead to mitochondrial damage, cytotoxicity and subsequent cell death. Hence, increasing ROS levels by either activating a ROS-generating enzyme or by depletion of antioxidants is a plausible strategy to induce cell killing in melanoma cells. The natural compound β-phenylethyl isothiocyanate (PEITC) found in cruciferous vegetables exhibits significant antitumor activity. Recent studies demonstrated that PEITC selectively induced cancer cell death by disabling the glutathione antioxidant system. Based on these observations, we hypothesize that PEITC may preferentially eliminate melanoma cells through ROS-mediated mechanism due to the increased basal ROS levels in melanoma cells and their high dependence on glutathione. To test this hypothesis, the cytotoxic effect of PEITC was tested in a panel of melanoma cell lines in comparison with normal melanocytes. Our results demonstrated that PEITC had time- and concentration-dependent antiproliferative effect in melanoma cells. The inhibitory effect is melanoma specific, since PEITC had minimum cytotoxic activity in normal melanocytes. Further analysis of ROS by FACS using the fluorescent dye DCFDA revealed that this cell death was primarily due to increased ROS accumulation triggered by PEITC-induced depletion of cellular glutathione. This aberrant increase in ROS caused mitochondrial membrane damage, as determined by biochemical analysis using Rhodamine 123, and subsequent cell death through apoptosis. Importantly, PEITC was very effective in melanoma cells, which exhibited resistance to standard anti-tumor drugs like temozolomide (TMZ) and carmustine (BCNU). Our study suggests that PEITC may be an effective anti-melanoma therapeutic agent that warrants further pre-clinical and clinical investigation. Our work is now directed towards identifying other ROS related cellular mechanisms that can be exploited to increase the therapeutic specificity and sensitivity of PEITC in melanoma cells. 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 2645. doi:10.1158/1538-7445.AM2011-2645
Risk of Cutaneous Carcinoma in Patients Treated with Oral Methoxsalen Photochemotherapy for Psoriasis
Authors: Robert S. Stern, Lawrence A. Thibodeau, Ruth A. Kleinerman, John A. Parrish, Thomas B. Fitzpatrick
Journal: New England Journal of Medicine (1979)

A 2.1-year prospective study of 1373 patients given oral 8-methoxypsoralen photochemotherapy for psoriasis revealed 30 patients with a total of 48 basal-cell and squamous-cell carcinomas. The observed incidence of cutaneous carcinoma was 2.63 (95 per cent confidence limits = 1.91 to 3.90) times that expected for an age, sex and geographically matched population. Relative risk to patients with history of ionizing radiation was 3.68 (99 per cent confidence limits, 2.42 to 8.69). Patients with a previous cutaneous carcinoma had a relative risk of 10.22 (99 per cent confidence limits, 4.78 to 37.08). A higher than expected proportion of squamous-cell carcinomas and an excess of squamous-cell carcinomas in areas not exposed to sun were seen. New patients with known histories of ionizing-radiation exposure or of skin tumors should be given 8-methyoxypsoralen photochemotherapy only if they understand the risks and have disabling psoriasis untreatable by other means.
Endoscopic management of esophageal bolus obstruction using the “oil immersion technique”
Authors: A. Schneider, W. Schepp
Journal: Endoscopy (2013)

Although the majority of esophageal bolus obstructions eventually clear spontaneously, some require medical interventions. Generally, endoscopists have to decide whether to push the bolus into the stomach or retrieve it by peroral extraction. Pushing may be preferred for objects that cannot be grabbed and extracted in their entirety [1] [2]. Peroral extraction is particularly advised for foreign bodies and in patients with a significant narrowing of the esophageal lumen that is causing the blockage distal to the bolus [3]. However, meat and vegetables in particular tend to undergo maceration, which makes retrieval and extraction laborious.
Abstract 3845: Developing a novel 3D model to study colon cancer cell invasion.
Authors: Rosie Adams
Journal: Cancer Research (2013)

Abstract Introduction: Colon cancer is the fifth most diagnosed in the UK, with nearly 22,000 cases diagnosed in 20101 with a five-year survival rate of 54.75%2. The formation of distant metastases also influences patient survival, causing a decline from 93% for the earliest stage tumours down to below 7% for tumours with distant metastases3. Previous literature has highlighted the limitations of two-dimensional (2D) cancer cell migration assays4. These include alterations in gene expression of cells and the provision of a migration substrate that does not closely reflect that of the in vivo environment. This project aims to mimic the in vivo situation to investigate factors that affect cancer cell invasion; including the expression of EMT markers and signalling by developing a three-dimensional (3D) model of colon cancer. Methods: This project utilises commercial scaffold known as Alvetex®5 and two colon cancer cell lines (SW480 and SW620) were used to look at the differences between pre- and post-metastatic colon cancer respectively. Both cell lines were cultured prior to analysis using various biochemical assays and histological processing. Results: Our data show a difference in cell penetration between the two cell lines. The later stage SW620 cells, which have a more motile phenotype in 2D, migrate and penetrate the scaffold to a greater extent than the earlier stage, less invasive, SW480 cells. This reflects a known difference in the level of EMT markers between the two cell lines, a result of the Wnt signalling pathway. This model also allows for the use of the known chemoattractant Insulin-like Growth Factor (IGF) to encourage cell penetration. IGF has been shown to play an important role in cancer cell migration. The use of IGF results in a 54% increase in cell penetration by the SW480 cell line, but not the SW620 cell line. Discussion: Our data shows great potential for further development of a 3D cancer invasion model using these scaffolds. This model provides a more realistic 3D environment and will be a tool for chemoattractant and co-culture studies to determine the mechanism of invasion utilised by these cells and to develop this model further to obtain an assay which is closer to the in vivo situation. Acknowledgements: This work was carried out with funding from the Grevillea Trust, Reinnervate Limited and BBSRC. Citation Format: Rosie Adams. Developing a novel 3D model to study colon cancer cell invasion. [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 3845. doi:10.1158/1538-7445.AM2013-3845