tbuckley/cabot-search huggingface dataset:
Abstract 3936: Expression of DNA Repair Factor DDB2 predicts chemoresistance in various cancer cell lines
Authors: Rishu Takimoto, Kazuyuki Murase, Yoshiyuki Onuma, Masahiro Hirakawa, Makoto Yoshida, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Junji Kato
Journal: Cancer Research (2010)

Abstract Accumulating evidence suggests that DNA repair enzyme activity may predict sensitivity to chemotherapeutic agents in cancer cells. The status of a DNA repair enzyme, such as XPF/ERCC4 or XPD/ERCC2, has been reported to serve as a prognostic indicator as well as an indicator of chemosensitivity. Another such candidate is the protein product of the DDB2 gene, p48, that interacts with the p127 protein to form the UV-damaged DNA binding complex (DDB). DDB2, a DNA repair factor induced by tumor suppressor p53, plays an important role in the nucleotide excision repair (NER) of UV-damaged DNA. Mice lacking DDB2 developed spontaneous tumors at a high rate, suggesting a tumor suppression function for DDB2. In this study, we hypothesized that DDB2 expression correlated with sensitivity to chemotherapeutic agents. To this end, we compared the cytotoxicity levels of DDB2-expressing and non-expressing cell lines upon exposure to chemotherapeutic agents. As a result, downregulation of DDB2 using siRNA restored chemosensitivity. DDB2 may be a molecular marker for prediction of chemosensitivity and a new target molecule for cancer chemotherapy. 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 3936.
New endoscopic suturing device for closure of chronic gastrocutaneous fistula in an immunocompromised patient
Authors: J. Armengol-Miro, J. Dot, M. Abu-Suboh Abadia, M. Masachs, J. Salord, J. Armengol Bertroli, A. Benages, S. Kantsevoy
Journal: Endoscopy (2011)

A 46-year-old man with AIDS received a percutaneous endoscopic gastrostomy (PEG) tube in October 2009. His condition improved, and the PEG tube was removed in May 2010. Afterwards, the patient developed a persistent gastrocutaneous fistula at the site of the previous PEG. Multiple attempts to close the fistula with endoscopic clips, gastropexy, and an over-the-scope clip (Ovesco Endoscopy AG, Tübingen, Germany) failed.
Regulated Expression of Diphtheria Toxin in Prostate Cancer Cells
Authors: Weidan Peng, Amy Verbitsky, Yunhua Bao, Janet A. Sawicki
Journal: Molecular Therapy (2002)

Despite their known potential for effectively killing cells, the therapeutic use of plant and bacterial toxins for the treatment of cancer has been slow to enter the clinical setting. This has been due in large part to the lack of gene regulatory elements that control expression of highly toxic genes in a sufficiently tight manner, such that the toxins are only expressed in specific target cells. "Leaky" promoters result in unwanted and harmful cell death. In this study, we tested a novel gene therapy strategy aimed at expressing diphtheria toxin (DT-A) in androgen-independent prostate cancer cells that express the protein BCL2. This strategy relies on both transcriptional regulation and inducibly regulated DNA recombination mediated by the site-directed Flp recombinase to control expression of the toxin. Adenoviruses are used to introduce the genetic elements required for this approach into cultured cells and xenografts. Administration of 4-hydroxytamoxifen, resulting in recombination and expression of the toxin, effectively kills the cancer cells. Our results suggest that following androgen ablation therapy for the treatment of prostate cancer, use of a regulated recombination system to target expression of DT-A to androgen-independent cancer cells would be an effective way to arrest the development of recurrent tumors. Despite their known potential for effectively killing cells, the therapeutic use of plant and bacterial toxins for the treatment of cancer has been slow to enter the clinical setting. This has been due in large part to the lack of gene regulatory elements that control expression of highly toxic genes in a sufficiently tight manner, such that the toxins are only expressed in specific target cells. "Leaky" promoters result in unwanted and harmful cell death. In this study, we tested a novel gene therapy strategy aimed at expressing diphtheria toxin (DT-A) in androgen-independent prostate cancer cells that express the protein BCL2. This strategy relies on both transcriptional regulation and inducibly regulated DNA recombination mediated by the site-directed Flp recombinase to control expression of the toxin. Adenoviruses are used to introduce the genetic elements required for this approach into cultured cells and xenografts. Administration of 4-hydroxytamoxifen, resulting in recombination and expression of the toxin, effectively kills the cancer cells. Our results suggest that following androgen ablation therapy for the treatment of prostate cancer, use of a regulated recombination system to target expression of DT-A to androgen-independent cancer cells would be an effective way to arrest the development of recurrent tumors.
ESTUDIO MULTICÉNTRICO DE SEGURIDAD EN EL TRATAMIENTO ENDOSCÓPICO DE LA OBESIDAD
Authors: E Espinet, J Nebreda, G López-Nava, J Ducóns, M Rodríguez Téllez, J Crespo, C Marra-López
Journal: Endoscopy (2014)

Introducción: La endoscopia bariátrica está considerada como una técnica emergente y específica que no está exenta de complicaciones mayores ni demandas judiciales, cuya incidencia y motivos son desconocidos.
Fortnightly Review: Vascular dementia
Authors: K. Amar, G. Wilcock
Journal: BMJ (1996)

<h3>Summary points</h3> Symptomatic stroke increases the risk of dementia more than ninefold Vascular dementia is one of the three commonest causes of dementia Above the age of 85 years it may be commoner than Alzheimer9s disease Vascular dementia may be caused by multiple infarcts, white matter ischaemia, or a strategically placed infarct All patients with possible vascular dementia need careful assessment to detect any underlying causes and risk factors that might be remediable
Cis -splicing and Translation of the Pre- Trans -splicing Molecule Combine With Efficiency in Spliceosome-mediated RNA Trans -splicing
Authors: François Monjaret, Nathalie Bourg, Laurence Suel, Carinne Roudaut, Florence Le Roy, Isabelle Richard, Karine Charton
Journal: Molecular Therapy (2014)

Muscular dystrophies are a group of genetically distinct diseases for which no treatment exists. While gene transfer approach is being tested for several of these diseases, such strategies can be hampered when the size of the corresponding complementary DNA (cDNA) exceeds the packaging capacity of adeno-associated virus vectors. This issue concerns, in particular, dysferlinopathies and titinopathies that are due to mutations in the dysferlin (DYSF) and titin (TTN) genes. We investigated the efficacy of RNA trans-splicing as a mode of RNA therapy for these two types of diseases. Results obtained with RNA trans-splicing molecules designed to target the 3' end of mouse titin and human dysferlin pre-mRNA transcripts indicated that trans-splicing of pre-mRNA generated from minigene constructs or from the endogenous genes was achieved. Collectively, these results provide the first demonstration of DYSF and TTN trans-splicing reprogramming in vitro and in vivo. However, in addition to these positive results, we uncovered a possible issue of the technique in the form of undesirable translation of RNA pre-trans-splicing molecules, directly from open reading frames present on the molecule or associated with internal alternative cis-splicing. These events may hamper the efficiency of the trans-splicing process and/or lead to toxicity.
THU0187 Complement C4 gene polymorphisms, serum protein levels and protein functional activity in relationship with clinical manifestations in patients with systemic lupus erythematosus:
Authors: L.-A. Korswagen, J. Jacobs, D. Wouters, I. Bultink, A. Schilder, D. Hamann, A. Voskuyl
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The complement component C4 and its associated polymorphisms have a strong association with systemic lupus erythematosus (SLE). A low gene copy number (GCN) of C4 and its two isotypes (C4A and C4B) is a risk factor for SLE. At genetic level the C4 polymorphism has been studied in large groups of SLE patients of various ethnic origins. However, little is known about the relationship between these polymorphisms, serum protein levels, protein functional activity and clinical manifestations in SLE patients. <h3>Objectives</h3> The aim of this study was to assess C4 complement gene polymorphism, serum protein levels and protein functional activity in a cohort of SLE patients in relationship to clinical and serological manifestations. <h3>Methods</h3> Demographic data and ACR-criteria were collected in a cohort of 140 Dutch SLE patients (90% female, 69% Caucasian, mean age 42 yrs, mean disease duration 8.8 yrs). Measurements of total C4, C4A and C4B gene copy number, serum protein levels and protein functional activity were performed in SLE patients and in 104 healthy controls. Multiplex Ligation-dependent Probe Amplification (MLPA) assay, ELISA and functional C4 assay were used. [1,2] Statistical analyses were performed using Pearson’s chi square test, Mann-Whitney test and linear regression. <h3>Results</h3> A total C4 GCN of four was found in 35.7% of SLE patients, compared to 59.6% (p=0.0002) in controls. A GCN of less than four (i.e. a low GCN) was found in 55.7% (controls: 31.7%, p=0.0002); C4A and C4B deficiency (i.e. less than two copies) in 42.2% (controls: 25%, p=0.005) and 22.1% (controls: 33.6%, p=0.05) respectively. Median levels of serum protein and functional activity were significantly decreased in SLE patients versus controls, for both total C4 and the isotypes. As shown in table 1 presence of serositis was associated with lower C4A GCN as well as with lower C4A protein level and lower C4A functional activity. In addition associations were found between lower C4B protein level and lower C4B functional activity with presence of a history of nephritis, hemolytical anemia, anti-ds DNA and anticardiolipin antibodies. All these associations were also found in the Caucasian subgroup. <h3>Conclusions</h3> Complement C4 gene polymorphism, serum protein levels and for the first time also protein functional activity were studied in relationship to clinical and serological manifestations in SLE patients. The findings add to the understanding of the various phenotypes of systemic lupus erythematosus and advocate further studies in lupus nephritis patients. <h3>References</h3> Wouters D et al. Mol Immunol. 2009;46(4):592-600 Wouters D et al. Mol Immunol. 2007;44(16):3954 <h3>Disclosure of Interest</h3> None Declared
Effect of Prolonged Ethanol Ingestion on the Transport and Metabolism of Lipids in Man
Authors: Robert H. Schapiro, Robert L. Scheig, Gladys D. Drummey, Jack H. Mendelson, Kurt J. Isselbacher
Journal: New England Journal of Medicine (1965)

ETHANOL ingestion is often associated with abnormalities in the transport and metabolism of lipids.1 Clinical manifestations of these abnormalities include triglyceride accumulation in the liver and in the serum. Zieve2 has called attention to the development of hyperlipemia associated with jaundice, reticulocytosis and deposition of fat in the liver in some alcoholic patients. However, it is evident that fatty infiltration of the liver may occur in such patients in the absence of hyperlipemia.3 Experimental observations in animals have suggested that the effects of ethanol on lipid metabolism may be independent of dietary factors.1,4,5 The present study demonstrates that . . .
Abstract 2582: P2X7 receptor is functional in myeloma cell lines and myeloma patient cells and can be modulated by P2X7 receptor antagonists: Implications for myeloma therapy
Authors: Kathleen A. Donovan, Laurie Moon-Tasson, Alexander E. Hromockyj, Debra M. Meyer, John A. Lust
Journal: Cancer Research (2011)

Abstract Inflammation is a driving factor in the pathogenesis of many cancers including multiple myeloma. Myeloma is a plasma cell tumor whose early stages are characterized by cytokine dependent growth, predominantly driven by IL-6. We have demonstrated that IL-1β is a key inducer of IL-6 expressed by bone marrow stromal cells in a paracrine fashion. The P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed by cells of the hematopoetic lineage that has been shown to play a critical role in IL-1β processing and secretion. We investigated the role this receptor may play in the IL-1/IL-6 cytokine pathway in multiple myeloma. A panel of multiple myeloma cell lines was evaluated by RT-PCR for the expression of P2X7R mRNA. Levels of expression in ANBL-6, MM1S, U266, RPMI-8226 and KAS-6/1 were comparable to U937, a previously characterized P2X7R positive cell line. A newly derived plasmacytoma cell line, PCYT3, showed very low levels of message expression. The ability of ATP to trigger the processing and release of IL-1β by activation of the P2X7 channel was studied using KAS-Pro, a myeloma cell line stably transfected with a pro- IL-1β gene. IL-1β, measured by ELISA, was released in a dose dependent fashion in response to increasing amounts of ATP ranging from 1mM to 5mM. Three P2X7R specific antagonists were tested for their effect on ATP stimulated IL- 1β release from KAS-Pro; all 3 compounds demonstrated inhibition in a dose dependent manner with varying degrees of potency correlating with P2X7R inhibition. In addition fresh patient samples (15 multiple myelomas/ 4 smoldering myelomas/8 MGUS) were evaluated for inhibition of IL-1β release by the P2X7R antagonists through direct measurement of IL-1β by ELISA as well as by an indirect measurement of IL-1β induced IL-6 production by normal bone marrow stromal cells. Greater than 90% inhibition of IL-1β release was demonstrated in all MM &amp; SMM patients positive for IL-1β expression. IL-1β was not detected in any of the MGUS patients and therefore no affect of the inhibitors was observed. These results confirm the activity of functional P2X7 receptors on myeloma cell lines and in fresh patient samples and suggest a role for the use of P2X7 receptor antagonists in the therapy of myeloma. 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 2582. doi:10.1158/1538-7445.AM2011-2582
P1-04-09: Biphasic Effects of Docetaxel and Hedgehog Signaling Antagonists on Breast Cancer Tumor-Initiating Cells In Vivo.
Authors: X Zhang, RC Moraes, MM Landis, M-F Wu, SG Hilsenbeck, MM Cairo, R Toftgar, JC Chang, MT Lewis
Journal: Cancer Research (2011)

Abstract Recent data suggest the existence of a subset of breast cancer cells variously termed cancer stem cells, tumor-initiating, or tumor-propagating cells, that are capable of self-renewal and of regenerating tumors upon transplantation that are biologically consistent with the tumor of origin. These cells appear to be intrinsically resistant to systemic chemo- and radiation therapies and may therefore be responsible for treatment resistance, and disease recurrence. Several signal transduction networks have been implicated in normal and malignant stem cell self-renewal. These include those of the Hedgehog, Notch, Wnt, EGF, FGF families of ligands. Antagonists of these networks have become attractive targeted therapeutic agents. In this study, we evaluated two different Hedgehog signaling antagonists, one targeting Smoothened (the main membrane effector of activated signaling) and one targeting GLI1/2 (the two transcription factors mediating ligand response), for their ability to shrink patient-derived xenograft tumors and to affect the number or function of breast tumor-initiating cells in vivo. Both antagonists showed little effect as single agents, but could augment tumor shrinkage by docetaxel. However, these effects were only observed in those models showing evidence of canonical SMO/GLI-mediated signaling. In dilutional transplantation assays, both SMO or GLI targeted agents have a biphasic effect on the behavior of the tumor-initiating population such that large cell numbers yielded few tumors while intermediate cell numbers yielded tumors at a comparable rate as controls. These data suggest that combination therapy alters the functional state of stem cells in the context of larger cell numbers rather than targeting the tumor-initiating cell directly. These data therefore have significant relevance for the interpretation of ongoing clinical trials of hedgehog signaling inhibitors in solid tumors, including breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-09.
Abstract P1-01-26: Procoagulant biomarkers may direct axillary nodal surgery
Authors: H Shaker, NJ Bundred, E Glassey, CC Kirwan
Journal: Cancer Research (2012)

Abstract Background: Preoperative accurate staging of the axilla (through identifying invasive breast cancers with subclinical nodal metastases) will reduce the need for repeat axillary surgery. Tissue factor (TF) is overexpressed in cancer and is shed into the circulation leading to activation of the thrombin (extrinsic clotting) pathway. D-dimer is a fibrin degradation product and reliable systemic marker of thrombin pathway activation. TF and d-dimer are raised in breast cancer and may act as biomarkers to identify invasive cancer patients with undiagnosed lymph node (LN) metastases requiring axillary nodal clearance. Methods: Plasma d-dimer and TF were measured pre-operatively using ELISA in patients undergoing curative surgery and sentinel node biopsy (SNB) for invasive breast cancer (n = 125). D-dimer was considered to be raised if it was above the clinically used upper limit of normal of 500ng/ml and if TF was above 200pg/ml. D-dimer and TF were correlated with the presence or absence of axillary metastases at sentinel node biopsy. Results: Median age was 61 years (range 24–84). Mean invasive tumour size was 16.7 mm (range 1.6–70). One hundred and eleven (79%) invasive cancers were oestrogen receptor positive, 93 (67%) were progesterone receptor positive and 17(12%) were HER2 receptor positive. Pre-operative d-dimer was higher in LN positive (mean 599 ng/ml, 95% CI 415–864, n=32) versus LN negative (454ng/ml, 95% CI 400–514, n=93, p = 0.068) invasive cancer. TF was not significantly higher in LN positive cancer (vs LN negative), although TF did show weak correlation with d-dimer (r = 0.2, p = 0.03). Sixty eight patients (54%) had raised TF and 59 (47%) had raised d-dimer. On multivariate analysis (age, tumour size, invasive grade, ER status and presence of lymphovascular invasion as covariates) a raised pre-operative d-dimer combined with a raised pre-operative TF was a significant independent predictor of node positivity (odds ratio 6.43, CI 1.70–24.27, p = 0.006). Markers of systemic thrombin pathway activity (i.e. a combination of plasma d-dimer and TF) had a sensitivity of 91%, specificity of 32%, positive predictive value of 32% and negative predictive value of 92%. Conclusion: High levels of clotting activation are seen in breast cancer patients. Over 90% of patients with no axillary lymph node metastases had normal pre-operative levels of plasma TF and d-dimer. Combination of systemic markers of thrombin pathway activation may help predict axillary nodal involvement. The role of thrombin pathway activation in breast cancer metastasis is under ongoing investigation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-26.
Reply to Chun et al. (1)
Authors: H. Inoue
Journal: Endoscopy (2012)

I appreciate the interest of Chun et al. in these articles. Our article [1] and that of Gong et al. [2] reported excision of submucosal tumors using a submucosal endoscopic approach. The technical feasibility and clinical safety of submucosal endoscopy have already been established and reported in the treatment of achalasia (peroral endoscopic myotomy [POEM]) [3] [4] [5]. The removal of submucosal tumors originating from the proper muscle layer was developed as an extended application of submucosal endoscopy [1] [2]. The same technique has also been reported by Xu et al. [6]. These reports on the submucosal endoscopic approach for submucosal tumors [1] [2] [6] are not comparative studies that make comparisons with the direct approach method [7], and thus we do not conclude which method is superior to the other. Both techniques actually have advantages and disadvantages.
In Vitro Lymphocyte Stimulation by a Soluble Antigen from Malignant Melanoma
Authors: Ulrich W. Jehn, Larry Nathanson, Robert S. Schwartz, Mary Skinner
Journal: New England Journal of Medicine (1970)

The lymphocytes of seven patients with malignant melanoma were stimulated when cultured in vitro with extracts of autologous tumor. One patient had a cystic neoplasm, which contained an electrophoretically homogeneous protein. This substance stimulated the patient's own lymphocytes in vitro, as well as those from the other six patients. Lymphocytes from normal persons did not respond to tumor extracts or to the cystictumor fluid. The mitogenic material in the tumor fluid had the electrophoretic mobility of a beta globulin and could be separated from the bulk of melanin pigments by starch-block electrophoresis. The urine of this patient also contained a homogeneous protein that was mitogenic in the presence of lymphocytes from patients with melanoma. Gel-diffusion analysis using rabbit antiserums against the tumor fluid and urinary mitogen showed that they were antigenically identical.