tbuckley/cabot-search huggingface dataset:
AB0047 The effects of KV1.3 and IKCA1 potassium channel inhibition on calcium influx of human peripheral T lymphocytes in rheumatoid arthritis
Authors: G. Toldi, A. Bajnok, D. Dobi, A. Kaposi, L. Kovács, B. Vásárhelyi, A. Balog
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation and present a possible target for selective immunomodulation. <h3>Objectives</h3> We aimed to characterize the effects of lymphocyte potassium channel inhibition on peripheral blood T lymphocyte activation in rheumatoid arthritis (RA). <h3>Methods</h3> We took peripheral blood samples from 10 healthy individuals and 9 recently diagnosed RA patients receiving no anti-rheumatic treatment. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We also assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels. <h3>Results</h3> The peak of calcium influx in lymphocytes isolated from RA patients is reached more rapidly, indicating that they respond more quickly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. No difference was detected between Th1 and Th2 or CD4 and CD8 cells in the sensitivity to IKCa1 channel inhibition among lymphocytes of RA patients. However, specific inhibition of the Kv1.3 channel acts differentially on calcium influx kinetics in RA lymphocyte subsets. Th2 and particularly CD8 cells are inhibited more dominantly than Th1 and CD4 cells. <h3>Conclusions</h3> Inhibition of Kv1.3 channels does not seem to be specific enough in peripheral RA lymphocytes, since anti-inflammatory Th2 cells are also affected to a noteworthy extent. Further studies are needed to evaluate the therapeutic potential of lymphocyte potassium channel inhibition in RA. <h3>Disclosure of Interest</h3> None Declared
Abstract 2977: LSD1 is Required for Chromosome Segregation during Mitosis
Authors: Shuang Lv, Wenjuan Bu, Hong Jiao, Bo Liu, Lin Zhu, Hongchang Zhao, Ji Liao, Jing Li, Xingzhi Xu
Journal: Cancer Research (2010)

Abstract Dynamic methylation/demethylation of histones and non-histone proteins occurs during the cell cycle. Lysine-specific demethylase 1 (LSD1) exhibits diverse transcriptional activities through catalyzing demethylation of mono- and di-methylated histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show here that inhibition of LSD1 expression by siRNA leads to abnormal chromosomal segregation in unperturbed mitosis and abnormal centrosome duplication, and is associated with decreased protein levels of MAD2 and BUBR1. LSD1 positively regulates the BUBR1 and MAD2 promoter activity and maintains local monomethylation status of H3K9, which is a repressive histone mark for gene transcription. Expression of exogenous BUBR1 and MAD2 in LSD1-depleted cells partially rescues the defect of chromosome segregation. Our results suggest that LSD1 plays a role in chromosomal segregation during mitosis partially through transcriptional regulation of BUBR1 and MAD2. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2977.
Increased Concentrations of Cholestanol and Apolipoprotein B in the Cerebrospinal Fluid of Patients with Cerebrotendinous Xanthomatosis
Authors: Gerald Salen, Vladimir Berginer, Virgie Shore, Ivan Horak, Eva Horak, G. Stephen Tint, Sarah Shefer
Journal: New England Journal of Medicine (1987)

We investigated the effect of chenodeoxycholic acid on cerebrospinal fluid sterol and protein composition in six patients with cerebrotendinous xanthomatosis, a progressive neurologic disease, and in 11 control subjects. In the cerebrospinal fluid from the controls, the mean (+/- SD) levels of cholesterol and cholestanol were 400 +/- 300 and 4 +/- 7 micrograms per deciliter, respectively. The levels were almost 1.5 and 20 times higher in cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis. Cholestanol levels were also markedly elevated in the plasma of untreated patients, but their plasma cholesterol levels (215 +/- 61 mg per deciliter) were not different from control values. Treatment with chenodeoxycholic acid reduced cerebrospinal fluid cholesterol by 34 percent and cholestanol threefold. Plasma cholestanol levels also decreased sharply. Normal cerebrospinal fluid contained small quantities of albumin, apolipoproteins, and lecithin:cholesterol acyltransferase. In cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis, immunoreactive apolipoprotein B or apolipoprotein B fragment was increased about 100-fold and albumin about 3.5-fold; apolipoprotein AI, apolipoprotein D, and lecithin:cholesterol acyltransferase were 1.5 to 3 times more concentrated. Apolipoprotein AIV and apolipoprotein E concentrations were comparable to those in controls, and apolipoprotein AII was considerably decreased. During treatment, the concentrations of albumin and apolipoproteins AI and B declined. These results suggest that increased cerebrospinal fluid sterols are derived from plasma lipoproteins by means of a defective blood-brain barrier in patients with cerebrotendinous xanthomatosis. Therapy with chenodeoxycholic acid reestablished selective permeability of the blood-brain barrier and normalized the concentrations of sterol and apolipoprotein in the cerebrospinal fluid.
1266 HISTONE VARIANT MACROH2A1 KNOCK-OUT WORSENS HIGH FAT DIET-INDUCED SYSTEMIC INSULIN RESISTANCE, GLUCOSE INTOLERANCE AND HEPATIC STEATOSIS IN MICE
Authors: D. Koonen, V. Pazienza, J.R. Pehrson, M. Hofker, A.G. Ladurner, A. Greco, C. Podrini, M. Vinciguerra
Journal: Journal of Hepatology (2012)
Abstract 4221: Pregnancy associated mammary gland micro-chimerism indicates fetal progenitor integration in breast cancer
Authors: Sonya Aziz-Zaman, Viktoria Denes, Monika Pilichowska, Peter Geck
Journal: Cancer Research (2010)

Abstract The PURPOSE of this work was to use Y chromosome markers to investigate the hypothesis that (i) post-pregnancy mammary glands are chimeras that integrate stem cells from the fetus and (ii) these immature progenitors have a critical role in breast cancer. RATIONALE The exchange of fetal and maternal cells during pregnancy results in the integration of fetal, multipotent progenitors in the mother. The established fetomaternal microchimerism (MC) appears to be stable for life in most mothers. These cells, called Pregnancy Associated Progenitor Cells (PAPC) represent a surprising, third type of progenitor pool (in addition to embryonic- and adult stem cells), with major biological implications. Y chromosome markers (male fetus) detect the fetal lineage and were present in several maternal tissues. No data are available on fetal progenitors in the human mammary gland, although the hormonal regeneration-degeneration cycles render the mammary gland a prime target for the integration of circulating stem/progenitor cell. HYPOTHESIS Based on the above, we postulated that the fetal progenitor lineage is highly represented in the mammary gland with a critical role in breast cancer. Two biological outcomes were considered: (i) PAPC integration may correctly rejuvenate the stem cell pool and protects from breast cancer; (ii) differentiation programs in the fetal progenitor lineages fail and progress to breast cancer. Our major OBJECTIVE was to investigate if breast cancer is microchimerism related by using Y-chromosome markers in breast cancer samples to establish correlations with breast cancer. EXPERIMENTAL PROCEDURES We worked out the methodology for Y-marker detection in breast cancer samples from commercially available tissue-arrays. Methods for microdissection (laser and mechanical), DNA extraction and PCR for Y-specific sequences were optimized. We targeted two Y-specific genes: SRY (SOX3-unrelated regions) and DYS14 (a male marker for a TSPY pseudogene). We analyzed 65 samples mostly from invasive ductal breast carcinomas and 40 normal controls. SUMMARY OF RESULTS We found low level Y-representation in 17.5 % (7/40) of normal breast samples. We detected increased levels of Y markers in 33.8 % (22/65) of breast cancer tissues (integrated SRY and DYS14 data). Further studies to analyze clinical correlations are in progress. CONCLUSIONS The data suggest, for the first time, that fetal cells are able to integrate into the mammary gland. Furthermore, this integration event appears to coincide with breast cancer. The increased representation suggests potential involvement of fetal progenitor cells in the pathomechanisms of breast cancer. 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 4221.
Prenatal Diagnosis of X-Linked Hyper-IgM Syndrome
Authors: James P. DiSanto, Sophie Markiewicz, Jean-Francois Gauchat, Jean-Yves Bonnefoy, Alain Fischer, Genevieve de Saint Basile
Journal: New England Journal of Medicine (1994)

The inability to initiate switching from one immunoglobulin isotype to another is the hallmark of the hyper-IgM immunodeficiency syndrome1. Patients with this primary immune disorder, originally termed “dysgammaglobulinemia type 1,”2 usually present with recurrent bacterial infections, including otitis media and pneumonia. Additional clinical features include opportunistic infections, recurrent neutropenia, lymphoid hyperplasia, and autoimmune manifestations. Abnormalities of serum immunoglobulins include low levels or an absence of IgG, IgA, and IgE and normal or, more frequently, elevated levels of IgM and IgD. The hyper-IgM syndrome can be inherited in an X-linked or autosomal recessive fashion. The candidate gene for this disease . . .
Abstract P2-11-10: Prospective memory impairment in early breast cancer survivors: Finally homing in on the real deficit?
Authors: S Verma, B Collins, X Song, M Bedard, L Paquet
Journal: Cancer Research (2012)

Abstract Background There is still much debate about the impact of early breast cancer (EBC) treatment on memory functioning. One limitation of existing studies is that they are based on neuropsychological testing procedures which may not be sensitive enough to detect memory problems as encountered in daily life. In fact, no study has objectively assessed everyday memory performance in EBC. One crucial aspect of using memory in daily activities is to remember to do something at an appropriate time in the future without being asked to do so-defined as “prospective memory” (PM). Despite its importance for daily functioning, little is known about PM in EBC patients. Thus, we investigated whether EBC survivors who were within 1 year of having completed adjuvant chemotherapy have PM impairment in comparison to age-matched healthy controls. In addition, we evaluated the contributions of fatigue and depression to PM functioning. Methods We undertook a cross sectional quantitative case-control study (n = 80) comparing EBC patients from the Ottawa Hospital Regional Cancer Centre with age and education-matched healthy controls from the community. A standardized test of PM (Memory for Intention Screening Test) was administered to both groups. Impairment was defined as a score that fell 2 standard deviations below the mean performance of the control group. Standardized measures of depression (CESD) and fatigue (Fact-F) were also completed. Results Age was well balanced between the groups (case and control mean age 54y, p = .84). EBC patients performed more poorly than controls on the PM test (p &amp;lt; .001) and had a significantly higher rate of impairment (23% vs. 5%, McNemar χ2, p &amp;lt;.01, odds ratio=5.5, 95% CI=1.7745 to 17.1473). A series of hierarchical regressions showed that patients PM performance was affected by fatigue (p &amp;lt;.05), but not depression (p = .51). Conclusions The results demonstrate reduced memory performance in EBC survivors, with a specific impact on PM. Women who complain of ‘chemo fog’ should be evaluated carefully for PM deficits and their concerns should be acknowledged. An important finding from this study is the demonstration that fatigue is associated with memory deficits when memory as used in everyday life is evaluated. This finding which is suggestive of a common mechanism involved in fatigue symptoms and everyday memory disturbances raises the possibility that interventions targeted at improving fatigue may also improve memory functioning and quality of life in EBC survivors. Further longitudinal studies should be conducted to critically evaluate the role of chemotherapy by assessing PM before the initiation of chemotherapy and in EBC patients receiving only adjuvant hormonal therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-10.
Metastatic Malignant Fibrous Histiocytoma Infiltrating Sigmoid Colon
Authors: Wei-Jun Wei, Chen-Tian Shen, Hong-Jun Song, Zhong-Ling Qiu, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2015)

Metastatic malignant fibrous histiocytoma (MFH) in the colon is extremely rare, although MFH is one of the most common soft tissue sarcomas in adults. We report the case of a 45-year-old woman with metastatic MFH in the sigmoid colon, descending colon, and right lung with FDG PET/CT findings.
Abstract 252: Evaluating the role of STK33 kinase in mutant KRAS cells
Authors: Carol Babij, Amro Shehabeldin, Manory Fernando, Kim Quon, Paul Kassner, Astrid Ruefli-Brasse, Vivienne Watson, Flordeliza Fajardo, Yihong Zhang, James Zondlo, Yu Sun, Aaron R. Ellison, Cherylene Plewa, Isabelle Dussault, Josette Carnahan
Journal: Cancer Research (2011)

Abstract Tumors harboring KRAS mutations remain an elusive target for oncology therapeutics. A recent publication (Scholl et al 2009) described a high throughput cellular RNAi screen which suggested a synthetic lethal relationship between STK33 and mutant KRAS. STK33 is a member of the calcium/calmodulin kinase family with a poorly characterized function. Although no genetic alterations in the STK33 gene have been reported in cancer, inhibiting STK33 kinase activity could offer a novel therapeutic approach to target mutant KRAS tumors. Thus, we sought to validate whether the survival of cancer cell lines with mutant KRAS is dependent on STK33, in parallel with a program to identify small molecule inhibitors of STK33 (Zhang Y et al AACR 2011). We focused on mutant KRAS leukemia cells because of their reported dependence on STK33. Using a panel of siRNA, 50-80% knockdown of STK33 at the RNA and protein level was achieved in NOMO-1KRASG13D and SKM-1KRASK117N cells. However we did not observe any alteration in cell viability. In addition, putative STK33 downstream signaling, (phosphorylation of p70 S6K thr389 and RPS6 ser235/236) was unaltered by modulation of STK33 expression. In contrast, knockdown of KRAS caused a significant reduction in both viability and signaling in these cell lines, confirming their dependence on KRAS. A panel of 27 cancer cell lines was screened with an siRNA library representing 1500 druggable genes. STK33 siRNA had no significant effect on viability regardless of KRAS mutational status. As expected, knockdown of KRAS significantly reduced cell viability, especially in mutant KRAS cells. A kinase dead mutant STK33 was used to test the dependence on STK33 kinase activity in mutant KRAS cell lines. Transient over-expression of kinase dead STK33 in PANC-1KRASG12D and DLD-1KRASG13D cells had no effect on viability, nor on the phosphorylation of p70 S6K thr389 and RPS6 ser235/236. In summary we have been unable to confirm a synthetic lethal relationship between STK33 and KRAS. Our data do not support inhibition of STK33 as a promising therapeutic approach for targeting mutant KRAS tumors. 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 252. doi:10.1158/1538-7445.AM2011-252
SP0053 Working to participate equally
Authors: C. van Drogen
Journal: Annals of the Rheumatic Diseases (2013)

By accepting one's restrictions and focusing on one's potential, one can make a contribution to society that feels worthwhile. Patients with visible as well as patients with invisible restrictions face the risk of pitfalls if they adopt a passive attitude towards their possibilities. To be accepted equally is partly a matter of presenting oneself in a way that is acceptable to others. Awareness of this rule and being able to handle this can be an eye-opener and help. Everybody has something to offer. How far will society accept people with restrictions? What can be done about it? Courses of self management, job coaching, and actual project work with disabled will be shown. Is getting paid for work the only way to happiness? Patients should ask themselves how they need to progress, and if they want to make enough effort to reach their goal. Patient Social Leagues should take the initiative. They can play a crucial role in informing and stimulating patients to improve their quality of life. Patient Social Leagues should also make knowledge about different options for patients accessible to both the patients and medical professionals. The right attitude helps a patient to improve his Quality of Life. <h3>Disclosure of Interest</h3> None Declared
Abstract 3090: RREB1 is necessary for the proliferation of bladder cancer cell lines
Authors: Matthew D. Nitz, Michael A. Harding, Dan Theodorescu
Journal: Cancer Research (2010)

Abstract It is estimated that in 2009 nearly 71,000 Americans will be diagnosed with bladder cancer and over 14,000 will die of the disease (SEER Database). With few treatment advances we studied the Ral GTPases as possible therapeutic targets, finding that the Ral paralogs are necessary for cell migration, anchorage independent growth, and metastasis (Gildea et al., Cancer Res. 2002 Feb 15;62(4):982-5)(unpublished data). To investigate possible transcription factors downstream of Ral in the bladder cancer cell line UMUC3 we performed gene expression profiling on cells with siRNA to both Ral paralogs. Computational analysis identified a statistical over representation of RREB1 binding sites in the promoters of differentially expressed genes. Further analysis confirmed RREB1 to be a novel transcriptional effector of Ral (Oxford et al., Oncogene. 2007 Nov 1;26(50):7143-52.) However, the role of RREB1 in bladder cancer has yet to be studied. Genetic depletion of RREB1 in the bladder cancer cell lines UMUC3, KU7 and J82 show a statistically significant decrease in growth in vitro. Furthermore, we identified two previously unreported RREB1 isoforms in addition to the two identified in NCBI genbank. Stable expression of each RREB1 isoform individually in the UMUC3 cell line resulted in significantly faster growth rates. Our data is consistent with the recent identification of RREB1 as an oncogene in the Moloney Murine Leukemia Virus (MuLV) tumor model (Uren et al., Cell 2008;133:727-41.) Our preliminary findings suggest that RREB1 is necessary for the survival of bladder cancer cell lines. 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 3090.
Abstract 3012: The mechanism of UV-induced and prohibitin-mediated apoptosis
Authors: Qiong Wu, Shiyong Wu
Journal: Cancer Research (2012)

Abstract Ultraviolet B (UVB) light is a potential environmental carcinogen, which has been shown to cause various skin cancers. Normally, UV-damaged cells are eliminated by the self-protective apoptosis response. UVB-induced apoptosis can be regulated by modification of major lipid raft components, such as cholesterol and ceramide. Upon UVB irradiation, an alteration of lipid raft composition leads to the recruitment/activation of raft-associated proteins and initiates downstream apoptotic signaling pathways. To identify potential regulators of UVB-induced apoptosis, we used 2D gel electrophoresis to identify the raft proteins that are altered after UVB-irradiation. Our data shows that levels of several raft proteins, including prohibitin (PHB), were changed after UVB-irradiation. PHB plays a critical role in many cell functions, such as cell-cycle control, cell proliferation, senescence, development, apoptosis, and tumor suppression. However, no reports implicate PHB-mediated apoptosis upon UVB irradiation. We now demonstrate that while the total PHB expression does not change, PHB is enriched in lipid rafts after UVB irradiation. Immunoprecipitation analysis shows that UVB alters the binding ability of PHB, Raf, and Akt, and decrease PHB phosphorylation. PHB siRNA knockdown cells exhibited an increased phosphorylation of Akt and ERK, and increased cell apoptosis after UVB irradiation. Based on these results, we propose that PHB regulates UVB-induced apoptosis through lipid raft translocation and alteration of Akt and Raf/ERK signaling pathways. 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 3012. doi:1538-7445.AM2012-3012