tbuckley/cabot-search huggingface dataset:
Abstract 154: miRNAs in plasma of pancreatic cancer patients
Authors: Shadan Ali, Khaldoun Almhanna, Wei Chen, Philip A. Philip, Fazlul H. Sarkar
Journal: Cancer Research (2011)

Abstract Pancreatic cancer (PC) has the poorest overall survival rate among all human cancers, which is in part could be due to the lack of early diagnosis; however, there are no reliable tools for early detection of PC, emphasizing the need for the discovery of novel biomarkers. In the current study, we investigated the expression profile of microRNAs (miRNAs) in the plasma of 50 PC patients and compared with 10 normal volunteers. The data was further validated by quantitative real-time PCR and cell-based assays. Moreover, we have tested the biological significance of our findings from plasma miRNAs experimentally by assessing differential expression of miRNAs in two parental and four chemo-resistant human PC cell lines by miRNA profiling and quantitative RT-PCR. We found 37 miRNAs that were down-regulated and 54 were up-regulated in the plasma from patients diagnosed with PC. The expression of miR-21 was significantly higher, and the expression of let-7 family (especially let-7d) and miR-146a was significantly lower in PC. The higher expression of miR-21 predicted worse survival, and although the overall expression of let-7d was lower in PC, the lowest expression predicted better survival compared to PC patients with relatively higher expression of let-7. Interestingly, we also found that miR-21 family was markedly over-expressed in chemo-resistant PC cell lines, which was consistent with the plasma data from PC patients. Our previous studies showed increased expression of miR-21 with concomitant loss of PTEN expression, which is consistent with current findings showing the loss of three additional targets of miR-21 (PDCD4, Maspin and TPM1). These results suggest that identifying and validating the expression of miRNAs in newly diagnosed patients could serve as a potential biomarker for tumor aggressiveness. Based on our findings, we conclude that miR-21 expression may serve as a novel plasma biomarker for early detection of PC. Hence such miRNAs could be useful for the screening of high-risk patients, which may further lead to the development of novel strategies by which miR-21 could be targeted for future drug development. 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 154. doi:10.1158/1538-7445.AM2011-154
Case 38-1996
Authors: Allan H. Ropper, Angela M. Caliendo
Journal: New England Journal of Medicine (1996)

Presentation of CaseAn 18-year-old right-handed man was admitted to the hospital because of severe, persistent headache and the development of ataxia and slurred speech.The patient had been in good health until one week earlier, when he awoke with severe retro-orbital pain, bilateral frontal headache, and pain at the base of the skull, with photophobia. His pains were similar to those he had experienced during repeated bouts of sinusitis and occasional ear infections since the age of 12 years but were much more severe. Thereafter, the headache and retro-orbital pain awakened him from sleep, and he received minor relief . . .
A Never-Ending Battle
Authors: Vyjeyanthi S. Periyakoil
Journal: New England Journal of Medicine (2015)

Mr. M.'s remaining lifespan was mere weeks, but he vehemently refused pain medications. It wasn't surprising: such medications can cause coping strategies to crumble, and like many military veterans, Mr. M. was a prisoner of an ongoing inner war that raged silently in his head.
AB0112 Caspase-5 inhibitor suppresses pro-inflammatory gene expressions in fibroblast like synoviocytes from patients with rheumatoid arthritis
Authors: Y.-J. Kwon, T.-Y. Kim, S.-W. Lee, Y.-B. Park, S.-K. Lee, M.-C. Park
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Caspases form an evolutionarily conserved family of cytosolic, aspartate-specific, cysteine proteases. Beyond its role in apoptosis, certain caspases (caspase-1, -4, -5, -11 and -12) exert non-apoptotic functions, including cytokine maturation during innate immunity, cell differentiation, proliferation, and NF-κB activation. <h3>Objectives</h3> This study investigated expression of caspase-5 and effect of Z-WEHD-fmk, a selective caspase-5 inhibitor, on pro-inflammatory gene expressions and cellular proliferation in fibroblast-like synoviocyte (FLS) in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Synovial tissues were obtained from patients with RA during total knee replacement surgery then FLS were isolated and cultured. Expression of caspase-5 in rheumatoid FLS were measured after stimulation either without or with pro-inflammatory agents IL-1β (2 ng/mL), TNF-α (20 ng/mL), lipopolysaccharide (1000 ng/mL) by real-time quantitative RT-PCR. The involvement of caspase-5 in inflammation and cellular proliferaion was further examined by treating the cells with caspase-5 inhibitor Z-WEHD-fmk. The mRNA expressions of IL-1β, IL-6, IL-18, COX-2, MMP-9 and CCL-2 after caspase-5 inhibitor Z-WEHD-fmk treatment were determined by real-time quantitative RT-PCR, and FLS proliferation in response to caspase-5 inhibitor Z-WEHD-fmk treatment was measured by MTT assay. <h3>Results</h3> Caspase-5 mRNA expression in RA FLS was increased by all the pro-inflammatory agents compared to control. Caspase-5 inhibitor Z-WEHD-fmk treatment induced a reduction in mRNA expressions of IL-1β, IL-6, IL-18, COX-2, MMP-9 and CCL-2 from RA FLS. But, cellular proliferation of rheumatoid FLS was not suppressed by caspase-5 inhibitor Z-WEHD-fmk. <h3>Conclusions</h3> Caspase-5 inhibitor treatment inhibited suppressed various pro-inflammatory gene expressions. These results suggest that inhibition of Caspase-5 can be a novel therapeutic approach in human RA. <h3>References</h3> Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007;14:10 –22. Scott AM, Saleh M. The inflammatory caspases: guardians against infections and sepsis. Cell Death Differ. 2007;14:23–31. Lamkanfi M, Kalai M, Vandenabeele P. Caspase-12: an overview. Cell Death Differ. 2004;11:365–368. Schwerk C, Schulze-Osthoff K. Non-apoptotic functions of caspases in cellular proliferation and differentiation. Biochem Pharmacol 2003;66:1453-8. <h3>Disclosure of Interest</h3> None Declared
Abstract 2908: Function and regulation of peroxiredoxin proteins in doxorubicin-treated MCF-7 breast cancer cells.
Authors: Caitlin McDonald, Gregg Perlmutter, Kekoa Taparra, Jillian Muhlbauer, Julie Passarelli, Shelley A. Phelan
Journal: Cancer Research (2013)

Abstract The Peroxiredoxin (Prdx) family of genes encodes thiol-specific antioxidant proteins that protect cells from oxidative stress. Mammalian cells express six different Prdx proteins, and these proteins play a role in cell signaling, proliferation and apoptosis. Recent studies have shown that Prdx levels are elevated in many cancers, suggesting that Prdx upregulation may be an advantageous adaptation to the cancerous state. In the present study we investigated the expression and function of different Prdx proteins in untreated and doxorubicin-treated MCF-7 breast cancer cells, as well as noncancerous MCF-10A cells. We used real-time PCR and western blotting to examine Prdx expression in both cell lines, and also measured Prdx protein expression in doxorubicin-treated MCF-7 cells. In addition, we suppressed Prdx expression using transiently transfected siRNA and measured cell proliferation and apoptosis. Our results show that MCF-7 cells are significantly more resistant to cell death induced by the chemotherapy agent doxorubicin. We also found that five of the six Prdxs are overexpressed in MCF-7 cells at the mRNA and protein levels, and that serum deprivation reduced Prdx expression. Treatment of MCF-7 cells with doxorubicin altered expression of specific Prdxs, demonstrating a specific effect on these antioxidants. Transient transfection of MCF-7 cells with Prdx6 siRNA resulted in a marked reduction in Prdx6 suppression, with no change in other Prdx proteins. Suppression of Prdx6 in these cells led to reduced cell proliferation and increased susceptibility to doxorubicin-induced death. Similar studies are currently underway for the other Prdx proteins. Together, these findings suggest that Prdx overexpression in MCF-7 cells may be cytoprotective and that Prdxs may contribute to doxorubicin-resistance in these and other breast cancer cells. Citation Format: Caitlin McDonald, Gregg Perlmutter, Kekoa Taparra, Jillian Muhlbauer, Julie Passarelli, Shelley A. Phelan. Function and regulation of peroxiredoxin proteins in doxorubicin-treated MCF-7 breast cancer cells. [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 2908. doi:10.1158/1538-7445.AM2013-2908
LOW YIELD OF GENETIC TESTING FOR KNOWN VASCULAR CONNECTIVE TISSUE DISORDERS AMONG PATIENTS WITH FIBROMUSCULAR DYSPLASIA
Authors: Stacey L. Poloskey, Soo Hyun Kim, Ruchi Sanghani, Adeeb Al-Quthami, Patricia Arscott, Rocio Moran, Christina Rigelsky, Heather Gornik
Journal: Journal of the American College of Cardiology (2012)
Abstract 1489: The role of bone marrow adipocyte-induced HO-1 expression in prostate tumor survival in bone
Authors: Aimalie L. Hardaway, Mackenzie K. Herroon, Erandi N. Rajagurubandara, Audrey Turchick, Izabela Podgorski
Journal: Cancer Research (2012)

Abstract Prostate cancer (PCa) is the second leading cause of cancer deaths among men in the United States. Obesity, adipocyte-derived signals, and adipose tissue inflammation are major contributors to development of aggressive PCa, with higher recurrence and higher mortality rates. Bone is a primary site of metastasis of PCa and obese and overweight men have a three-fold higher risk of progression to metastatic disease compared to normal-weight men receiving the same treatment. Experimental and clinical evidence indicate that bone marrow adipocyte numbers increase with age and obesity and their increased presence affects homeostasis in the bone microenvironment. It is not, however, currently known how adipocyte-derived factors influence tumor growth and survival in bone. Heme oxygenase 1 (HO-1) is a stress-responsive protein induced by hypoxia and inflammation, and it has been shown to play a role in prostate carcinogenesis and cell survival. Its role in tumor cell aggressiveness and survival in response to adipocyte-derived signals has not been previously explored. Here, we investigated the effects of bone marrow adipocyte-derived factors on HO-1/IL-1α pathway in PCa cells. Our study was driven by hypothesis that adipocytes increase invasiveness and survival of PCa cells via upregulation of HO-1. We utilized Taqman RT PCR analyses and western blotting approaches to demonstrate that levels of HO-1 and its inducer IL-1α increase in PC3, DU145 and C42B prostate cancer cell lines in response to treatment with adipocyte conditioned media (Adipo CM). Immunofluorescence analyses and subcellular fractionation methods were used to demonstrate a translocation of HO-1 from the cytoplasm to nucleus upon exposure to Adipo CM. Invasiveness of PCa cells in response to adipocyte-derived factors in the absence and presence of IL-1α neutralizing antibody and HO-1 inhibitor Zinc protoporphyrin IX was assessed using Boyden chamber assays. Studies are currently underway to determine the significance of HO-1/IL-1α upregulation in tumor cells survival and response to chemotherapy. Collectively, the results of our studies demonstrate that adipocyte-induced upregulation of HO-1/IL-1α pathways may be playing a significant role in promoting prostate tumor aggressiveness and survival. 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 1489. doi:1538-7445.AM2012-1489
Abstract 3140: Constitutive and regulated expression of GPR109A by DNA methylation and IFN-γ in human colon carcinoma cells
Authors: Kankana Bardhan, Vadivel Ganapathy, Kebin Liu
Journal: Cancer Research (2012)

Abstract Butyrate, one of the short chain fatty acids generated in the colon by microbiota from dietary fiber, has shown both preventative and therapeutic potential to counteract inflammatory disease and inflammation-mediated colorectal cancer. GPR109A, a recently identified receptor for butyrate, is highly expressed in normal colonic tissue, but is often down-regulated in human colon carcinoma cells. The molecular mechanisms underlying regulation of GPR109A expression in human colon carcinoma cells is unknown. Here we demonstrated that although there is no CpG island in the human GPR109A promoter region, the GPR109A promoter is hypermethylated in human colon carcinoma cell lines and in colon carcinoma tissue specimens. Interestingly, despite the hypermethylation of the promoter, IFN-γ, a cytokine secreted by activated cytotoxic T lymphocytes (CTL), effectively up-regulated GPR109A expression in human colon carcinoma cells, and this regulation is mediated at the transcriptional level. Furthermore, we demonstrated that the IFN-γ-activated pSTAT1 regulates GPR109A expression by directly binding to the Gamma Activation Site (GAS) elements in the GPR109A promoter region in human colon carcinoma cells. At the functional level, IFN-γ-mediated up-regulation of GPR109A resulted in increased sensitivity of the tumor cells to butyrate-induced cell death and increased level of histone acetylation in human colon carcinoma cells. In summary, our data demonstrated that although GPR109A can be constitutively silenced by DNA methylation in human colon carcinoma cells, tumor-infiltrating CTLs might use secretion of IFN-γ to up-regulate GPR109A as a mechanism to re-activate GPR109A, thereby restoring functional response of colon carcinoma cells to butyrate in the tumor microenvironment. 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 3140. doi:1538-7445.AM2012-3140
Case 2-2009
Authors: Michael R. Filbin, David C. Ring, Michael R. Wessels, Laura L. Avery, Richard L. Kradin
Journal: New England Journal of Medicine (2009)

A 25-year-old man was transferred to the emergency department of this hospital because of pain and swelling of the right hand and hypotension. His hand was mottled and swollen, with a black eschar on the dorsum, and soft-tissue swelling extended up the proximal forearm. Vigorous fluid resuscitation and norepinephrine were required for hemodynamic support.
Abstract 3451: Gramicidin-based nanopores induce cellular energy depletion and cell death in renal cell carcinoma.
Authors: Justin M. David, Ayyappan K. Rajasekaran
Journal: Cancer Research (2013)

Abstract The plasma membrane physically separates the intracellular components of a cell from the extracellular environment and its integrity is absolutely essential to sustain cellular functions. Ionophores are lipid soluble organic molecules that disrupt cellular transmembrane potential by rendering biological membranes permeable to specific ions. They are classified on the basis of their mechanism of action; mobile carriers complex with metal cations to shield their hydrophilic charge from the interior of the lipid bilayer and channel-formers insert into the membrane to form hydrophilic pores that permit the rapid passage of selected ions through membranes. Research over the past decade has described an new role for mobile carrier ionophores as novel anticancer therapeutics yet the potential anticancer attributes of channel-forming ionophores have not been explored. In this study we utilized the channel-forming ionophore gramicidin A (GA) as a model nanopore to study its effects upon the growth and survival of renal cell carcinoma (RCC) cells. RCC is a histologically heterogeneous malignancy that is highly resistant to conventional chemotherapy. We found that disruption of plasma membrane integrity with GA reduced the in vitro viability of several RCC cell lines when treated at sub-micromolar concentrations (all IC50 &amp;lt; 1.0μM). Comparison of GA with the mobile carrier ionophore monensin revealed that cell viability was decreased by GA to a degree that was equal to or greater than monensin depending on the cell line. Mechanistic examination determined that GA induced cell death that was associated with cellular energy depletion. Importantly, GA exhibited similar toxicity in RCC cells regardless of histological subtype or the expression of either the von Hippel-Lindau (VHL) tumor suppressor or its downstream target hypoxia-inducible factor (HIF) -1α. Taken together, these results demonstrate the utility of nanopore-forming drugs as a new strategy for cancer therapy. Citation Format: Justin M. David, Ayyappan K. Rajasekaran. Gramicidin-based nanopores induce cellular energy depletion and cell death in renal cell carcinoma. [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 3451. doi:10.1158/1538-7445.AM2013-3451
Australian paediatric guidelines already acknowledge hypoglycaemia as an indicator of good diabetes care
Authors: Clever Banda
Journal: BMJ (2016)

Rodriguez-Gutierrez and colleagues emphasise that diabetes guidelines in the UK and US, except for those from the US Department of Veterans Affairs, focus on hyperglycaemia as a quality measure at the expense of hypoglycaemia and re-iterate the adverse effects of hypoglycaemia on health.1

The Australia Paediatric Endocrine …
AB1219 Outcome of pediatric patients with end stage renal disease secondary to systemic lupus erythematosus in croatia in the last four decades
Authors: Ž. Mustapic, Z. Puretic, J. Slavicek, M. Frkovic, M. Jelusic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> to evaluate outcome of pediatric patients with end stage renal disease (ESRD) due to lupus nephritis and to determine has intensive specific treatment in SLE decreased incidence of ESRD and need for renal replacement therapy (RRT), dialysis and kidney transplantation, in pediatric patients in the last four decades in Croatia. <h3>Methods</h3> we evaluated basic data from national registry of pediatric patients (under the age of 18 years) receiving renal replacement therapy for ESRDin a period of 1972-2011. Data were collected from three major tertiary clinical centers performing RRT in pediatric patients. <h3>Results</h3> Since 1972, 156 children, 96 boys (61%) and 70 girls (39%), received RRT for ESRD. Seven of them, 3 girls and 4 boys, secondary to SLE (4%). Median age in these children when RRT was initiated was 15 years. 6 children started with hemodialysis in 1972-2002, and two of them died while waiting for kidney transplantation. Since 2002, only one child needed RRT (peritoneal dialysis) and has been succesfuly transplanted. At the same period of time, 27 children with SLE was treated with plasmapheresis, and only 2 of them in the last 10 years. <h3>Conclusions</h3> Our findings indicate that change in initial therapies improved outcome of children with SLE as well as need for dialysis or kidney transplantation in recent years. We also found that therapeutic plasmapheresis is used significantly less frequent probablydue to increased availability of powerful immunosuppressive drugs such as mycophenolate mofetil and azathioprine. <h3>Disclosure of Interest</h3> None Declared
Abstract 1635: Combination of the HDAC inhibitor romidepsin with the MEK inhibitor U0126 results in synergistic plasma cell apoptosis
Authors: Yanyan Gu, Jonathan Kaufman, Lawrence H. Boise, Sagar Lonial
Journal: Cancer Research (2010)

Abstract Histone deacetylase inhibitors such as vorinostat and panobinostat have been tested as single agents in patients with relapsed myeloma with nominal activity. Yet, when combined with the proteasome inhibitor bortezomib, clinical and laboratory evidence of synergy has been observed. We sought to evaluate the individual signaling effects of the HDACi romidepsin, with the intent of developing additional combinations that may lead to clues of mechanism of action on human myeloma cells. Single agent studies demonstrated IC50 values for romidepsin alone of between 10 and 30nm, further experiments demonstrate that growth inhibition resulting from romidepsin exposure includes apoptosis and cell cycle arrest. Cell death is associated with increased caspase 3, 8, 9 and PARP cleavage. Cell cycle analysis indicates that romidepsin induces G0/G1 cell cycle arrest which is correlated with p21 upregulation. Cell signaling assessment demonstrates that romidepsin inhibits AKT phosphorylation. Surprisingly, romidepsin increases Erk phosphorylation with its resultant effects on cell growth, development and differentiation. Combining romidepsin with the MEK inhibitor U0126 suppresses MEK/ERK signaling, and synergistically enhances the antitumor effect of romidepsin (combination index value &amp;lt;1). Annexin V staining demonstrates significant apoptosis following 18 hr of treatment with U0126 (5µM) and 10nM romidepsin. Western blot confirms the development of significantly increased procasepase and PARP cleavage, as well as substantial downregulation of Mcl-1, Bcl-xL. The combination can overcome the antiapoptotic effect of exogenous cytokines, such as IL-6 and IGF1 in vitro. Further studies evaluating the effect of bone marrow stromal cells will be presented in addition of data evaluating other potential targets for oncogene addiction that can be used for further novel combinations to gain more understanding of the biological context of this combination both in vitro and in vivo. This study will improve the design of effective clinical combination strategies. 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 1635.