tbuckley/cabot-search huggingface dataset:
Abstract 3933: Collagen-proteinase cross-talk promotes gemcitabine resistance in pancreatic cancer
Authors: Surabhi Y. Dangi-Garimella, Hidayatullah G. Munshi
Journal: Cancer Research (2010)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival of ∼5%. A hallmark of PDAC is desmoplastic reaction (DR), the pronounced stromal reaction composed of extracellular matrix proteins along with activated fibroblasts, immune cells and endothelial cells. Although it has been suggested that the DR may be responsible for drug resistance, the mechanism is not well deciphered. We now show that collagen type I, the major component of DR, helps PDAC cells override the cell cycle checkpoint arrest induced by gemcitabine, the most commonly used chemotherapy for PDAC. Relative to cells grown on tissue culture plastic, PDAC cells grown in 3D type I collagen gels demonstrated decreased activating phosphorylation of the checkpoint protein Chk1 following gemcitabine treatment. Interestingly, PDAC cells grown atop 3D collagen gels were more sensitive to gemcitabine treatment and demonstrated higher phospho-Chk1 levels compared to cells growing within 3D collagen gels, suggesting that collagen functions as a barrier to drug delivery. As we had previously shown that collagen could induce expression of the key collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) by PDAC cells, we examined the contribution of MT1-MMP to drug resistance in our model system. Downregulating MT1-MMP with siRNA attenuated the effect of collagen on gemcitabine-induced checkpoint arrest. In contrast, MT1-MMP overexpression further protected the cells from gemcitabine-induced checkpoint arrest. Overall, our results demonstrate the complex interplay between the proteinase MT1-MMP and its substrate type I collagen in regulating chemotherapy resistance, and suggests that targeting MT1-MMP could help overcome PDAC drug resistance. 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 3933.
Should protein intake be restricted in predialysis patients?
Authors: Mackenzie Walser, William E. Mitch, Bradley J. Maroni, Joel D. Kopple
Journal: Kidney International (1999)

There are also no data supporting the second assumpIn the last decade, two findings have cast doubt on tion, with the obvious exception of starting dialysis in the wisdom of administering low-protein diets to CRF severely uremic patients. The third assumption is also patients: First, a large body of evidence has documented unsupported by the literature: Protein nutrition of CRF that hypoalbuminemia in dialysis patients is a major risk patients is usually maintained or improved by low-profactor for mortality, whether present at the onset of tein or supplemented very low protein diets. Hence, a dialysis or developed during dialysis [4‐19]. Other indi- well-planned, low-protein diet not only maintains or imces of nutritional status, such as urea nitrogen appear- proves nutritional state (including serum albumin levels) ance and predialysis levels of creatinine and cholesterol, in predialysis patients, but by reducing symptoms, it also are also correlated with mortality [4‐19]. Second, the delays the need for dialysis. Moreover, substantial evihypothesis that protein restriction slows the progression dence suggests that it may also slow the rate of progresof CRF (another rationale for its use) has not been un- sion of renal insufficiency. equivocally confirmed (discussed later here). As a result The benefits of a nutritional regimen include the folof these findings, some workers have questioned the lowing: (a) reduction in (or delayed onset of) symptoms wisdom of restricting protein intake [20‐22]. Further- and signs of uremia; (b) forestalling complications by more, they have suggested that if spontaneous protein lowering the accumulation of waste products at any given intake falls below 0.8 g/kg/day, patients are at increased level of glomerular filtration rate (GFR); and (c) perhaps risk of malnutrition, and the appropriate response is to slowing the rate of decline of GFR. Objections that have start dialysis unless protein intake can be increased. The been raised include cost, poor compliance, and perhaps assumptions underlying these recommendations are that: the increased risk of malnutrition. In this article, we (a) protein nutrition will improve in predialysis patients review the evidence supporting each of these benefits, if protein intake increases; (b) dialysis improves dietary as well as the evidence for each of these objections. intake and nutritional status; and (c) low protein intake causes malnutrition in predialysis patients.
Caractéristiques et facteurs pronostiques des angiodysplasies coliques hémorragiques: étude prospective multicentrique de l'ANGH
Authors: S Nahon, G Macaigne, EA Pariente, B Bour, E Saillard, A Boruchowicz, O Danne, JC Arnal, J Danis, JL Badetti
Journal: Endoscopy (2010)

But: Les angiodysplasies coliques sont habituellement responsables d'anémie ferriprive. Le but de ce travail est de décrire les caractéristiques cliniques et les facteurs pronostiques des angiodysplasies coliques responsables d'hémorragie digestive basse (HDB).
Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation
Authors: Dominique Bluteau, Alessandra Balduini, Nathalie Balayn, Manuela Currao, Paquita Nurden, Caroline Deswarte, Guy Leverger, Patrizia Noris, Silverio Perrotta, Eric Solary, William Vainchenker, Najet Debili, Remi Favier, Hana Raslova
Journal: Journal of Clinical Investigation (2014)

Point mutations in the 5′ UTR of ankyrin repeat domain 26 (ANKRD26) are associated with familial thrombocytopenia 2 (THC2) and a predisposition to leukemia. Here, we identified underlying mechanisms of ANKRD26-associated thrombocytopenia. Using megakaryocytes (MK) isolated from THC2 patients and healthy subjects, we demonstrated that THC2-associated mutations in the 5′ UTR of ANKRD26 resulted in loss of runt-related transcription factor 1 (RUNX1) and friend leukemia integration 1 transcription factor (FLI1) binding. RUNX1 and FLI1 binding at the 5′ UTR from healthy subjects led to ANKRD26 silencing during the late stages of megakaryopoiesis and blood platelet development. We showed that persistent ANKRD26 expression in isolated MKs increased signaling via the thrombopoietin/myeloproliferative leukemia virus oncogene (MPL) pathway and impaired proplatelet formation by MKs. Importantly, we demonstrated that ERK inhibition completely rescued the in vitro proplatelet formation defect. Our data identify a mechanism for development of the familial thrombocytopenia THC2 that is related to abnormal MAPK signaling.
Thyroid Dysfunction in Uremia: Evidence for Thyroid and Hypophyseal Abnormalities
Authors: GERMAN RAMIREZ
Journal: Annals of Internal Medicine (1976)

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to exogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.
The effects of RO-22-4679, a thromboxane synthetase inhibitor, on ventricular fibrillation induced by coronary artery occlusion in conscious dogs.
Authors: C B Huddleston, F M Lupinetti, K H Laws, J C Collins, J A Clanton, J J Hawiger, J A Oates, J W Hammon
Journal: Circulation Research (1983)
1200 CHARACTERIZATION AND IDENTIFICATION OF PPI-437, PPI-668 AND PPI-833 AS POTENT AND SELECTIVE HCV NS5A INHIBITORS WITH ACTIVITY AGAINST ALL HCV GENOTYPES
Authors: R. Colonno, N. Huang, Q. Huang, E. Peng, A. Huq, M. Lau, M. Bencsik, M. Zhong, L. Li
Journal: Journal of Hepatology (2011)
Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine
Authors: Lynda M. Foltz, Bakul I. Dalal, Louis D. Wadsworth, Raewyn Broady, Kim Chi, Elizabeth Eisenhauer, Ken Kobayashi, Christian Kollmannsburger
Journal: American Journal of Hematology (2006)

We report occurrence of severe methemoglobinemia in a patient on novel experimental anti-cancer drug, Triapine. Treatment with methylene blue led to massive hemolysis due to concomitant G6PD deficiency. We recommend that G6PD screening be done in high-risk populations prior to commencement of Triapine therapy. Am. J. Hematol. 81:210–211, 2006. © 2006 Wiley-Liss, Inc.
Esophageal nitinol stent dysfunction because of fracture and collapse
Authors: S. Rana, D. Bhasin, G. Sidhu, P. Rawal, B. Nagi, K. Singh
Journal: Endoscopy (2009)

A 40-year-old man, a long-term smoker, presented with progressively increasing dysphagia associated with loss of appetite and weight. The general physical and systemic examination was normal. Routine investigations, including hemogram, blood biochemistry and a chest radiograph were also normal.
Abstract 1216: The Fn14 receptor is highly expressed in NSCLC tumors and in NSCLC cell lines harboring EGFR-activating mutations
Authors: Nhan L. Tran, Kaushal Asrani, Nathan Jameson, Landon Inge, Emily Cheng, Galen Hostetter, Glen Weiss, Serdar Tuncali, Ross Bremner, Jeffrey A. Winkles
Journal: Cancer Research (2011)

Abstract Lung cancer is the leading cause of cancer deaths in the USA and worldwide and ∼85% of these cancers are of the non-small cell lung cancer (NSCLC) subtype. Approximately 10-15% of the NSCLC patients in the USA and 30-50% of these patients in Asia have tumors harboring somatic mutations in the epidermal growth factor receptor (EGFR) that cause constitutive activation of this receptor. These patients have the best clinical response to the small molecule EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. Here we report that the TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) is frequently overexpressed in NSCLC tumors. We have also found that NSCLC cell lines that contain the same EGFR activating mutations found in patients express high levels of Fn14. Erlotinib treatment of these cells decreases Fn14 levels; therefore, EGFR signaling is indeed triggering Fn14 gene expression in these cell lines. Consistent with this proposal, when EGFR activation mutant receptors (L858R, ΔL747-E749, and D770-N771 insertion) were expressed in rat RL65 lung epithelial cells Fn14 expression was induced. In contrast, RL65 cells expressing a kinase-deficient EGFR receptor (D837A) did not show an increase in Fn14 expression. Since some NSCLC tumors with EGFR activating mutations acquire an additional EGFR mutation (T790M) that promotes TKI resistance, we examined Fn14 levels in a cell line containing both types of mutations. The Fn14 receptor was expressed at high levels in these cells. Finally, we found that shRNA-mediated Fn14 knockdown reduces NSCLC cell migration. Together, these data indicate that EGFR activation in NSCLC cells increases Fn14 gene expression and that Fn14 levels remain elevated in drug resistant cells. Furthermore, Fn14 may play a role in NSCLC cell motility. We propose that Fn14 may be a good biomarker for selection of NSCLC patients most likely to benefit from EGFR TKIs. It may also be a therapeutic target for NSCLC patients; in particular, for those patients with EGFR-driven tumors who have either primary or acquired resistance to EGFR tyrosine kinase inhibitors. 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 1216. doi:10.1158/1538-7445.AM2011-1216
Abstract 1992: Is the ubiquitin ligase WWP2 playing a role in PTEN degradation in endometrial cancer.
Authors: Aine Clements, Joseph McElroy, Adrian Suarez, Sarmila Majumder, David Cohn, Gustavo Leone
Journal: Cancer Research (2013)

Abstract Objective: The ubiquitin ligase WWP2 has recently been described to directly interact with PTEN, the major tumor suppressor gene in the PI3K pathway commonly altered in endometrial cancer. Whether alterations of WWP2 contribute to post-translational modifications of the PTEN protein in endometrial cancer are unknown. We sought to determine if WWP2 gene expression levels differ in human endometrial cancer tissues with evidence of post-translational PTEN degradation. We also wished to determine if elevated WWP2 gene expression was associated with clinical prognostic variables. Methods: Twenty-four endometrial cancer specimens collected at hysterectomy were available for analysis. These tumors were stained for PTEN by immunohistochemistry (IHC) and scored using a scale of 0-6. Frozen tissue was then used to determine PTEN and WWP2 expression by Real time PCR (RT PCR). Gene expression was then compared with findings on immunohistochemistry. Patient clinical characteristics including stage, grade, lymph node metastases, recurrence or 2 year disease status were then compared with PTEN and WWP2 expression. Results: Three tumors had elevated PTEN gene expression (at least 2 fold) but low (score of less than 4) PTEN protein on IHC, indicating post-translational modification of PTEN. In these tumors, however, WWP2 expression was not elevated (range 0.004-0.09). There were three tumors with elevation in WWP2 expression (1.9-4.7). PTEN was low in these tumors on IHC, but was also low by RT-PCR indicating genomic, epigenetic or post-transcriptional modification of PTEN. Neither PTEN nor WWP2 expression on RT PCR was associated with stage, grade, lymph node metastases, recurrence or 2 year disease status. Conclusions: In this cohort of tumors, WWP2 did not contribute to post-translational degradation of PTEN. WWP2 expression was not associated with stage, grade, lymph node metastases, recurrence, or 2 year disease status. Citation Format: Aine Clements, Joseph McElroy, Adrian Suarez, Sarmila Majumder, David Cohn, Gustavo Leone. Is the ubiquitin ligase WWP2 playing a role in PTEN degradation in endometrial 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 1992. doi:10.1158/1538-7445.AM2013-1992
Abstract 4493: Preclinical efficacy of AZD8055, an ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitor, in vitro in urothelial carcinoma of the bladder
Authors: Kelly Y. Lin, Gopal N. Gupta, Carole Sourbier, Heinric Williams, Sylvie Guichard, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Cancer Research (2011)

Abstract Mammalian target of rapamycin (mTOR) has been shown to play a key role in energy sensing, cell growth, and cell survival in many cancers. Although alterations of the PI3K/Akt/mTOR pathway are frequent in urothelial carcinoma (UC), the effects of pharmacologic targeting of this pathway have not been systematically evaluated. Selective inhibitors of the mTORC1 component of mTOR have modest activity in renal cell cancer and are currently being evaluated in patients with advanced bladder cancer. Since selective mTORC1 inhibition may lead to feedback activation of Akt through mTORC2, concomitant disruption of mTORC2 activity may result in more complete mTOR blockade and more potent antitumor activity than inhibition of mTORC1 alone. In this study, the efficacy of the dual mTORC1/mTORC2 inhibitor AZD8055 was compared with that of rapamycin in three UC cell lines UMUC-3, TCCSuP and HT-1376. Both AZD8055 and rapamycin were able to downregulate the mTORC1 substrate pS6; however, only AZD8055 was effective in downregulating p4E-BP1, a critical component of cap-dependent translation that is also regulated by mTORC1. AZD8055, but not rapamycin, potently suppressed mTORC2 signaling as evidenced by downregulation of pAKTs473. AZD8055 exhibited potent in vitro antitumor activity against all three bladder cancer cell lines, with IC50s of 15-40nM by the MTT assay, while rapamycin had minimal antitumor activity at these concentrations (IC50 not reached at 1uM). In vivo efficacy of AZD8055 is under evaluation in mouse xenograft models. These data demonstrate that AZD8055 is a potent inhibitor of mTORC2 and a more effective inhibitor of downstream mTORC1 targets than rapamycin. Combined mTORC1/2 kinase inhibition may be superior to selective mTORC1 inhibition, and is worthy of clinical evaluation in urothelial carcinoma of the bladder. 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 4493. doi:10.1158/1538-7445.AM2011-4493
Breath methane and large bowel cancer risk in contrasting African populations.
Authors: I Segal, A R Walker, S Lord, J H Cummings
Journal: Gut (1988)

Breath methane has been measured in 1016 people from four populations resident in Southern Africa which experience widely different risks of bowel cancer and other colonic diseases. Highly significant differences in the proportion of subjects with detectable methane in breath were found; % producers--rural black 84, urban black 72, white 52, Indian 41 (chi 2 121 p less than 0.001 3 df). There was a slight preponderance of female producers over male (female producers 63%, males 57%) and an age trend with fewer producers in the older age groups in the urban blacks and Indians, these comparisons being significant when tested by stepwise logistic regression analysis. Bowel cancer risk, determined from a variety of sources, was lowest in rural blacks, greatest in whites, with intermediate rates for urban blacks and Indians. Methane production in the human colon shows significant interethnic differences but which bear no relation to bowel cancer risk in these populations.
Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects
Authors: Heikki Swan, Matti Viitasalo, Kirsi Piippo, Päivi Laitinen, Kimmo Kontula, Lauri Toivonen
Journal: Journal of the American College of Cardiology (1999)
Abstract LB-237: Human and microbial transcriptomics from lean and obese individuals with colorectal cancer: A comparison of Total and Poly A RNA sequencing from clinical samples.
Authors: Desma M. Grice, Denis C. Bauer, Konsta Duesing, Dongmei Li, Paul Greenfield, Sarah Nielsen, Brian Draganic, Steve Smith, Peter Pockney, Rodney Scott, Garry N. Hannan
Journal: Cancer Research (2013)

Abstract Australia and New Zealand have the highest worldwide CRC incidence with CRC being the 2nd most commonly diagnosed cancer and the 3rd most common cause of cancer death among both men and women. CRC is a complex disease arising from the impact of environmental factors, including diet and lifestyle choices on different genetic backgrounds. Obesity and type 2 diabetes are significant risk factors for CRC, the levels of which are increasing in Australia. As a consequence CRC is projected to increase, being the most common Australian cancer by 2025. While the association of obesity with CRC has been reported by a number of studies, the mechanism\s that contribute to CRC development in the context of obesity are unknown. Understanding these mechanisms and potential genetic susceptibility is crucial for developing effective intervention and screening strategies. Recent evidence suggests that gut microbial communities are altered in obese individuals, resulting in a change in the predominant species and overall loss of community diversity but it is unknown if these changes impact CRC development or progression. We have established a comprehensive tissue, blood and microbial collection from 150 lean and obese colorectal cancer patients in the Hunter Region, Australia and commenced an integrative pilot next generation sequencing project to begin to unravel the link between obesity and CRC. Twelve individuals (6 lean and 6 obese) were selected for complementary next-generation sequencing; generating matched sequencing data sets (Total RNA-seq, Poly A RNA-seq, microbial RNA-seq and exome-seq) from normal colon, colon tumor, adipose and digesta samples samples. For this purpose, we have developed a method for simultaneously isolating human and microbial RNA from gut lumen of sufficient quality and quantity from limited material. Results presented will evaluate the differences in host and microbial transciptomics in normal colon and tumor tissue of lean and obese individuals with CRC and methodological comparisons between Total RNA-seq and Poly A RNA-seq will be reported. Citation Format: Desma M. Grice, Denis C. Bauer, Konsta Duesing, Dongmei Li, Paul Greenfield, Sarah Nielsen, Brian Draganic, Steve Smith, Peter Pockney, Rodney Scott, Garry N. Hannan. Human and microbial transcriptomics from lean and obese individuals with colorectal cancer: A comparison of Total and Poly A RNA sequencing from clinical samples. [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 LB-237. doi:10.1158/1538-7445.AM2013-LB-237
STUDIES ON THE SUPRARENAL CORTEX
Authors: George A. Harrop, Albert Weinstein
Journal: The Journal of Experimental Medicine (1933)

1. The methods used in the operation and care of suprarenalectomized dogs are given. 2. The effect of injections of the cortical hormone upon normal and suprarenalectomized dogs is described. 3. Symptoms and chemical studies of suprarenal insufficiency in the dog, following extract withdrawal are described, together with the effects produced by its readministration. 4. The phenomena associated with experimental suprarenal insufficiency are contrasted with those seen in patients with Addison's disease. The identity of the acute symptoms with those of "shock" is pointed out.
Psychomimetic effects of pentazocine and dihydrocodeine tartrate.
Authors: M Taylor, D B Galloway, J C Petrie, J F Davidson, S C Gallon, D C Moir
Journal: BMJ (1978)

a diet sheet in English had had the diet satisfactorily explained compared with three out of four who received a sheet in the native language and seven out of the I 1 who received a sheet in both languages.Therefore 48 of those given diet sheets had them satisfactorily explained-the same proportion as had altered their eating habits.
Medical Devices: Significant vs Nonsignificant Risk-Reply
Authors: Stephen A. Streed
Journal: JAMA (1995)

<h3>In Reply.</h3> —We are pleased that Ms Segal's IRB is knowledgeable about the issues discussed in our article. The fact that it was inconceivable to her that our problem developed is irrelevant. The reason the article was written was that it did happen to us and that a survey of other similar institutions demonstrated to us that it could happen to others as well. Perhaps the process by which IRBs become aware of relevant FDA regulations needs to be more standardized so that such disparities in knowledge between IRBs will not occur. Dr Huffaker feels that the FDA makes it too difficult for manufacturers to modify medical devices and his implication is that we agree with them. We did not actually address the level of FDA regulation that should exist to oversee the modification of medical devices. We focused on the lack of understanding of the medical community related to