tbuckley/cabot-search huggingface dataset:
Abstract 3606: Gene and miRNA expression profiles in lung cancer cells cooperated with drug sensitivity to PKC inhibitor enzastaurin
Authors: Seike Masahiro, Tetsuya Okano, Tsuneo Shimokawa, Akihiko Gemma
Journal: Cancer Research (2010)

Abstract PKC-beta inhibitor, Enzastaurin, is being evaluated in a Phase III trial as a maintenance therapy for the treatment of diffuse large B-cell lymphoma (DLBCL), as well as being evaluated in several Phase II studies across a variety of more common tumor types including: breast, colon, lung, ovarian and prostate cancers. Sequence-dependent, synergistic antiproliferative and proapoptotic effects of the combination of cytotoxic drugs and enzastaurin in non small cell lung cancer cells (NSCLC). To ascertain the potential for PKC-beta inhibitor-based treatment in NSCLC, we analyzed the antitumor effects of enzastaurin in 22 NSCLC cell lines via MTT assay. To identify a molecular model of sensitivity to PKC-beta inhibitor treatment in NSCLC, we conducted a gene and miRNA expression profiling study using cDNA arrays and Taqman MicroRNA Arrays on the same set of cell lines and related the cytotoxic activity of enzastaurin to corresponding gene and miRNA expression pattern. In addition, pathway analysis was done with Pathway Architect software. We used eight genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. We also identified unique miRNA expression patterns correlated with enzastaurin sensitivity. Our results suggested that PKCβ inhibitor may be promising anticancer drugs to NSCLC and the eight-gene classifier is useful in predicting drug sensitivity to PKC-beta inhibitors and may contribute to achieving individualized therapy for NSCLC patients. 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 3606.
Tc-99m Ethyl Cysteinate Dimer SPECT and 2-[F-18]fluoro-2-deoxy-D-glucose PET in Alzheimer's Disease
Authors: K Ishii, M Sasaki, S Sakamoto, S Yamaji, H Kitagaki, E Mori
Journal: Clinical Nuclear Medicine (1999)

Purpose: This study compared Tc-99m ethyl cysteinate dimer (ECD) SPECT images with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) PET images in the same patients with Alzheimer's disease and determined whether ECD SPECT is as useful as FDG PET clinically. Methods: Ten patients with probable Alzheimer's disease (mean ± SD: age, 71 ± 5.2 years; 6 women and 4 men; Mini-Mental State Examination score, 19.2 ± 5.3) were evaluated in this study. Both ECD SPECT and FDG PET were performed within 1.5 months in each patient. Results: ECD SPECT showed a reduction in parietotemporal perfusion in 8 of the 10 patients, whereas FDG PET showed a reduction in temporoparietal metabolism in 9. The ECD images showed greater radiotracer uptake in the cerebellum and occipital lobe than did FDG images. The contrast between the radiotracer uptake in the sensorimotor area and that in the parietotemporal region was not as great in the ECD images as it was in the FDG images. Conclusion: Although ECD SPECT may not be superior to FDG PET, it is useful for the clinical evaluation of patients with Alzheimer's disease.
Lymphosarcoma of the Bowel in Childhood
Authors: George D. Cutler, Richard B. Stark, H. William Scott
Journal: New England Journal of Medicine (1945)

PRIMARY neoplasms of the large or small intestine are extremely rare in childhood as compared with those in adult life. Except for true adenomatous polyps, most intestinal tumors encountered in early life are sarcomatous. Lymphosarcoma is one of the more frequent types of this group, and it is the purpose of this paper to describe our experience with this tumor in children under twelve years of age, as well as a case of reticulum-cell sarcoma.PathologyLymphosarcoma was separated from the general group of lymphoma in 1893 by Kundrat,1 who described it as a highly malignant tumor of lymphoid tissue . . .
Abstract 4491: Transforming growth factor (TGF) ≤ pathway and clinical outcome of pancreatic cancer
Authors: Milind M. Javle, Xiaoqun Dong, Dongfeng Tan, Yanan Li, Siddhartha P. Kar, Veera Baladandayuthapani, Jacqueline Weatherly, Sunil Krishnan, Tzu-chuan J, None Huang, David R. Fogelman, James L. Abbruzzese, Robert A. Wolff, Donghui Li
Journal: Cancer Research (2012)

Abstract Background: TGFβ acts both as a tumor suppressor or tumor promoter depending upon cellular context and stage of tumor progression. TGFβ exerts its effects through the TGFβR1/ R2 receptors and the SMAD transcription regulators. We investigated the prognostic value of TGFβ signaling biomarkers in pancreatic cancer. Methods: We measured plasma TGFβ1 level using Meso Scale Discovery Multi-array® Human TGFβ1 Assay in 643 pancreatic cancer patients. TGFβR2 (Novus) and SMAD4 (Proteintech) protein expression were measured in 86 biopsies using immunohistochemisty (IHC). IHC intensity was scored 0-3. Percentage IHC-positive cancer cells were 0-3 (0: 0%+, 1: 1-10%+, 2: 10-25%+, 3: &amp;gt;25%+). Final IHC score was measured as intensity × percentage. We also genotyped 3 SNPs of TGFB1 gene using the Taqman assay. Kaplan-Meier and log-rank tests were used to analyze overall survival (OS) by TGFβ1 level. Multivariate Cox proportional hazards models with relevant clinical covariates were used to assess the relationship between IHC score and OS. Results: In patients with locally advanced and metastatic disease (n = 355), there was a significant association of plasma TGFβ1 with OS. OS of the top quartile of TGFβ1 levels (&amp;gt;19.05 ng/mL) vs. those with low level was 27.7 weeks vs. 40 weeks, respectively [log-rank p = 0.0125, adjusted for baseline CA 19-9 and performance status (PS)]. No significant association between plasma TGFβ1 and OS was noted in surgical patients (n = 288). In the multivariate Cox model, after adjusting for baseline stage, CA 19-9, PS, age and TGFβR2 expression, complete loss of SMAD4 expression (IHC score 0) was significantly associated with lower OS [HR (95% CI): 1.85 (1.06-3.23), p = 0.03]. Progressive disease on gemcitabine-based therapy was more likely in SMAD4 IHC 0 group as compared with higher score (46.5% vs. 38.1% progressed; chi square p = 0.069). TGFB1 –1346T&amp;gt;C CT/TT genotype correlated with shorter OS [HR (95% CI): 1.21 (1.02-1.45), p = 0.03] after adjusting for clinical variables. Conclusions: This large retrospective study suggests an important stage-dependant role of the TGFβ pathway in pancreatic cancer. Targeting this pathway in advanced pancreatic cancer may have therapeutic relevance. 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 4491. doi:1538-7445.AM2012-4491
Memorable patients: Down but not out
Authors: M K Thong
Journal: BMJ (1998)

A decade ago my first house officer posting was in a paediatric ward in a Malaysian general hospital. One of my patients was a 2 year old Malay boy with Down's syndrome who had been referred for hypercyanotic spells. He was a scrawny looking kid with the deepest cyanosis I had ever seen. What made him stand out in the busy paediatric ward was his sunny smile for everyone who passed his cot. He had been referred 12 months earlier for cyanotic spells and when Tetralogy of Fallot was diagnosed he was sent home to a rural village to await a date for palliative surgical treatment. I discovered much later that the number of names on the paediatric cardiac surgery list was longer than anyone …
Acute Regional Enteritis in Children
Authors: Robert C. Storrs, Robert A. Hoekelman
Journal: New England Journal of Medicine (1953)

BOTH the acute and chronic forms of regional enteritis have been well known pathologic entities in adults for the past twenty years. However, surprisingly little has been written about either form of the disease occurring in children.Crohn, Ginzburg and Oppenheimer1 presented the original description of regional enteritis in 1932, including both the acute and chronic forms. They reported 14 cases of chronic regional enteritis. The youngest patient in this series was seventeen years old. In a later paper, Crohn2 reported 11 cases of acute terminal ileitis and stated that he had not seen a case of the disease occurring . . .
Abstract 1418: Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through down-regulation of NF-kappa-B activity
Authors: kuramoto takuya
Journal: Cancer Research (2012)

Abstract Purpose: The Notch signaling regulates cell-fate decisions during development and postnatal life. Recent studies have demonstrated that the signaling through Notch and its ligand Dll4 in tumor endothelial cells plays an important role in cancer angiogenesis. Little is known, however, about the role of Dll4-Notch signaling between cancer cells, and how it affects on cancer metastasis. We therefore assessed the importance of cancer cell Dll4-Notch signaling in cancer metastasis produced by human small lung cancer cells. Experimental Design: On the basis of previous studies, we generated retroviral vectors encoding a soluble dimerized form of Dll4 fused to the human IgG1 Fc constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch interactions. Dll4-Fc was introduced into human small cell lung cancer cell lines that express high level of Dll4 and Notch (SBC-3 and H1048 cells), and low level of Dll4 (SBC-5 cells). The cells were intravenously inoculated to natural killer cell-depleted SCID mice, and the multiple-organ metastases were evaluated. Result: The number of liver metastasis in the mice inoculated with SBC-3 and H1048 cells expressing Dll4-Fc were significantly lower than that of liver metastasis formed by control transfectant cells. However, the number of liver metastasis formed by SBC-5 cells was not significantly different between Dll4-Fc expressing and control cells, suggesting that Dll4-Notch signaling in cancer cells plays important role in liver metastasis of small cell lung cancer. Metastatic colonies in other organ such as lung, kidney and bone were not affected by Dll4-Fc overexpression in each cell lines. In order to study the molecular mechanism of the effect of Dll4-Fc on liver metastasis, genes associated with metastasis were screened by PCR array system. Seven genes (MMP7, IL1B, MMP1, S100A4, MMP10, CXCR4, SERPINE1) were down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048, but not SBC-5 cells, compared with control transfectant cells. Since most of the selected genes were NF-kappa-B target genes, we explored whether NF-kappa-B is involved in cancer cell Dll4-Notch signaling. By using luciferase assay, we observed that NF-kappa-B activity was down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048 cells, but not SBC-5 cells, compared with control transfectant cells, indicating that Dll4-Fc inhibits NF-kappa-B activity in small cell lung cancer cells by suppressing Dll4-Notch signaling. Conclusion: These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of small cell lung cancer, by regulating the NF-kappa-B signaling. 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 1418. doi:1538-7445.AM2012-1418
P685Reorganization of Kir2.x ion channel complex under stress effects on cardiomyocytes and neuronal cells
Authors: V Szuts, D Borcsok, F Otvos, HR Kozak, M Szuts, L Toth, E Welker, A Szekeres, T Papp, CS Vagvolgyi
Journal: Cardiovascular Research (2014)

Background: Kir2.x channels are important regulators of resting membrane potential and cellular excitability of both the cardiac and neuronal cells underlying the structural base of IK1. Ophiobolins are sesterterpene-type secondary metabolites of fungi and these posses with antitumor, antibacterial, antifungal activities. Aim and methods: In this study we examined the contribution of Kir2.x ion channels with modulator and its possible contribution to electrophysiological remodelling in the presence of ophiobolins. We compared the expression of Kir2.x ion channel complex using molecular biological techniques in cardiomyocytes and neuronal cell lines.
More than meets the eye: esophageal invasive mucinous adenocarcinoma masquerading as a submucosal lipoma on endoscopic ultrasound
Authors: Dennis Yang, Lizette Duckworth, Peter Draganov
Journal: Endoscopy (2014)

Endoscopic ultrasound (EUS) is considered to be the most accurate method of locoregional staging of advanced but potentially curable esophageal lesions [1]. This report describes a case of a mucinous adenocarcinoma arising in the setting of Barrett's esophagus with benign endosonographic features mimicking a lipoma.
Eyes Wide Open
Authors: Emma C. Morton-Bours, Michael B. Jacobs, Gregory W. Albers
Journal: New England Journal of Medicine (2000)

Six days after he was found on the floor with altered consciousness, a 51-year-old man went to see his physician. The episode was associated with emesis and fecal incontinence. The patient reported feeling confused for approximately 30 minutes after the incident. He also had severe weakness in both legs and was unable to walk for 24 hours.Altered consciousness associated with incontinence and transient confusion is most suggestive of a seizure. However, persistent weakness of the legs is unusual after a seizure and raises other diagnostic possibilities. Ischemia in the posterior circulation can produce weakness of the legs . . .
Focal Myocarditis Associated with Pheochromocytoma
Authors: Peter D. Van Vliet, Howard B. Burchell, Jack L. Titus
Journal: New England Journal of Medicine (1966)

MYOCARDIAL lesions have been described in patients who had received catecholamines for prolonged periods before death,1 2 3 4 and similar lesions have been produced in the myocardium of laboratory animals by the administration of norepinephrine3 and epinephrine.5 Myocardial lesions might thus be expected in patients harboring a functioning pheochromocytoma, but only a few morphologic studies of myocardial lesions in such patients have been reported.2 , 6 Since cardiovascular disorders are often predominant causes of death in patients with pheochromocytoma7 the hearts of such patients were reviewed in search of myocardial lesions. In addition, experimental lesions were produced in the myocardium of rats by the . . .
The evaluation value of fuzzy classification of EUS texture features in the therapy of radioactive seeds implatation in pancreatic cancer
Authors: Liu Yan, Hu Yuhong, Wu Yi-jun, Yu Jian-guo, Jin Zhen-dong
Journal: Endoscopy (2011)

Aims: Eus-guided radioactive seeds implantion has been found to be effective that may improve quality of life and survival in patients with advanced unresectable pancreatic cancer. The evaluation of it's effects remains a challenging clinical problem.
P01.16 * MICROGLIA/MACROPHAGES AS CELLULAR TARGET OF NOVEL CXCR4 ANTAGONIST IN A GLIOMA MODEL
Authors: L. Mercurio, M. Ajmone-Cat, S. Cecchetti, A. Ricci, L. Portella, P. Amodeo, R. Vitale, S. Scala, L. Minghetti, G. Carpinelli
Journal: Neuro-Oncology (2014)

BACKGROUND: The CXCL12/CXCR4 signaling pathway has been recently described regulating proliferation, metastasis and angiogenesis in several solid tumors, including brain malignances and modulate the cross-talk between tumor and microenvironment. In gliomas recent studies demonstrated that tumor cells attracts surrounding microglia/macrophages into the tumour mass polarizing infiltrating microglia into an anti-inflammatory, immunosuppressive, proangiogenic phenotype (M2) that promote cancer growth, in this context CXCL12 acts as chemoattractant and contributes to suppress anti-tumor immunity, favoring the M2 phenotype polarization. Aim of this study was to evaluate the effects mediated by a novel CXCR4 antagonist, Peptide R, on tumor microenvironment in an orthotopic human glioblastoma multiforme (GBM) model. MATERIAL AND METHOD: Studies were performed using intracranial xenografts of U87MG GBM cells injected in CD1 nude mice. Peptide R (CNR and INT G. Pascale, Naples) (2mg/kg) was administered for 15-20 days since U87MG cells implantation. To evaluate glioma growth, tumor volume was assessed by magnetic resonance imaging (MRI) analyses, performed at 4.7 T. Confocal Laser Scanning Microscopy (CLSM) analyses on brain sections were conducted to analyze expression of markers identifying microglia/macrophages (CD11b, CD68) and markers associated to pro-inflammatory microglial phenotype (M1) or immunosuppressive phenotype (M2), respectively inducible nitric oxide synthase (iNOS) and Arginase-1 (Arg-1). Moreover we examined vascular endothelial growth factor, VEGF and endothelial marker expression (CD31). RESULTS: AND DISCUSSION: Confocal analyses of brain sections showed a modulation of reactivity and spatial distribution of microglia/macrophages in response to Peptide R, as detected by CD11b/CD68 double staining treatment. We reported a reduction in the number of CD11b+ cells recruited at the tumor-edge, together with an increased percentage of CD11b+ cells expressing iNOS, pro-inflammatory phenotype of microglia, in tumor core. At the same time, in peptide R-treated animals we observed reduced Arg-1 expression, by intratumoral endothelial structures, but not in CD11b + /Arg-1 cells. Furthermore Peptide R induced a drastic inhibition of VEGF and CD31 expression in tumor core. CONCLUSION: Our results showed that the new antagonist Peptide R induced alterations on tumor microenvironment favoring the acquisition of pro-inflammatory features in a GBM xenograft model creating a niche less favorable to the tumor growth. Modulation of CXCL12/CXCR4 axis in GBM may prove to be an important therapeutic strategy to interfere with the crosstalk between tumor and surrounding cellular microenvironment.
VALIDATION OF PHASE ANALYSIS DIAGNOSIS OF REGIONAL WALL MOTION ABNORMALITIES BY MAGNETIC RESONANCE IMAGING.
Authors: K. D. Thomas, E. W. Akins, R. J. Subbiondo, J. R. Fitzsimmons, C. M. Williams
Journal: Clinical Nuclear Medicine (1984)

Thomas, K. D.; Akins, E. W.; Subbiondo, R. J.; Fitzsimmons, J. R.; Williams, C. M. Author Information
Clinical Outcomes after Transfusion-Associated Hepatitis C
Authors: Myron J. Tong, Neveen S. El-Farra, Andrew R. Reikes, Ruth L. Co
Journal: New England Journal of Medicine (1995)

The extent of serious complications in people who have acquired chronic hepatitis C infection after a blood transfusion is unclear.We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal.The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent) had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional seven patients an average of 36 months (range, 7 to 121) after the initial visit. During follow-up, 20 patients (15.3 percent) died: 8 from complications of cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma; and 1, with chronic active hepatitis, from pneumonia.In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.
Abstract LB-466: Genomic Loss of microRNA 491 contributes to IGFBP2 overexpression and stemness in GBM
Authors: Xia Li, Yuexin Liu, Ping Ji, Yingxuan Chua, Limei Hu, Fei Guo, Yan Sun, Frederick Lang, Wei Zhang
Journal: Cancer Research (2012)

Abstract Insulin-like growth factor-binding protein 2 (IGFBP2) is overexpressed in 80% of glioblastoma multiforme (GBM, WHO grade IV). Our mouse model experiments demonstrated that IGFBP2 is a glioma oncogene. However, the underlying mechanism for overexpression of IGFBP2 remains unknown. We examined a total of 388 GBM samples from the Cancer Genome Atlas (TCGA) and found that miR-491, which is located on chr9p21.3, is deleted in 57% of cases. TargetScan analysis revealed that there is a binding site of miR-491 on the 3′-UTR of the IGFBP2 gene. The miR-491 expression levels in GBM patients are inversely correlated with that of IGFBP2. We validated this regulatory relationship by overexpression of miR-491 and observed down-regulation of IGFBP-2 in both protein level and mRNA level in U251 and T98G glioma cell lines. Conversely, miR-491 inhibitors increased IGFBP2 in LN229 cells which express low level of endogenous IGFBP2. Luciferase reporter assay further proved that IGFBP2 is a direct target of miR-491. Moreover, ectopic expression of miR-491 inhibited cell migration and invasion of U251 and T98G as efficiently as knockdown of IGFBP2 and such inhibitory effects can be partially reversed by overexpression of IGFBP2-EGFP in U251, supporting the notion that IGFBP2 plays an important role in miR-491's functions. To investigate the role of miR-491 in stemness of GBM, we introduced miR-491 into 3 patient-derived glioma stem cell lines and found that miR-49 downregulated CDK6 and Bcl-xL and inhibited neurosphere formation and cell proliferation. These findings suggest that miR-491 acts as a tumor suppressor miR by coordinately attenuating multiple oncogenes in GBM. Our results provide new insights into the mechanism for oncogenic IGFBP2 overexpression and may provide new opportunities for therapeutic strategies for GBM treatment. 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 LB-466. doi:1538-7445.AM2012-LB-466