tbuckley/cabot-search huggingface dataset:
P402 UNDERSTANDING THE MECHANISMS UNDERPINNING TREATMENT NON-RESPONSE IN PRIMARY BILIARY CIRRHOSIS: A TOOL FOR TREATMENT STRATIFICATION
Authors: A.C. Pitts, J.M. Palmer, J.K. Dyson, S. Ducker, L. Griffiths, D.E.J. Jones, J.A. Kirby
Journal: Journal of Hepatology (2014)
Abstract 5209: Abrogation of STAT3 activation by JSI-124 enhances dasatinib-induced cytotoxicity in malignant human glioma cell lines
Authors: Esther P. Jane, Daniel R. Premkumar, Naomi R. Agostino, Joseph L. Scialabba, Ian F. Pollack
Journal: Cancer Research (2010)

Abstract Src family kinases (SFK) collectively regulate a variety of cellular functions in many cancer types including proliferation, invasion, motility, survival, differentiation, and angiogenesis. Src greatly enhances EGFR-mediated transformation, raising the possibility that Src and/or its related family members may be effectors of EGFR signaling in cancer, including in glioblastoma. Although Dasatinib (BMS-354825), an ATP-competitive, small molecule tyrosine kinase inhibitor, suppresses the activity of SFKs at nanomolar concentrations, IC50 values ranged from 7 to 30 µM for inhibition of proliferation, well above the clinically achievable range. Because Src kinases were initially implicated in STAT activation, we hypothesized that the combination of Src inhibitor dasatinib and JAK2/STAT3 inhibitor JSI-124 would promote glioma cytotoxicity by decreasing both the activation status of c-Src and STAT3, as well as downregulating the levels of other relevant signaling effectors. We, therefore, examined the effects of dasatinib and JSI-124, alone or in combination, on signal transduction, migration and apoptosis in a series of malignant human glioma cell lines. JSI-124 significantly enhanced the efficacy of dasatinib in vitro. Combination of dasatinib and JSI-124 displayed a significant inhibition of cell migration in all cell lines. The effects on cell migration correlated with the inhibition of Src and downstream mediators of adhesion (e.g. focal adhesion kinase). Cells exposed to dasatinib and JSI-124 induced morphological changes that were consistent with an upstream role for Src in regulating focal adhesion complexes. Taken together, targeting Src and STAT pathway may contribute to the treatment of cancers that demonstrate increased levels of EGFR, Src and STATs, including malignant human glioma 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 5209.
Successful Radioimmuno-therapy for Lung Metastasis of Human Colonic Cancer in Nude Mice
Authors: R. M. Sharkey, K. S. Weadock, A. Natale, L. Haywood, R. Aninipot, R. D. Blumenthal, D. M. Goldenberg
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Successful Radioimmuno-therapy for Lung Metastasis of Human Colonic Cancer in Nude Mice Get access Robert M. Sharkey, Robert M. Sharkey Search for other works by this author on: Oxford Academic PubMed Google Scholar Kevin S. Weadock, Kevin S. Weadock Search for other works by this author on: Oxford Academic PubMed Google Scholar Ana Natale, Ana Natale Search for other works by this author on: Oxford Academic PubMed Google Scholar Lemuel Haywood, Lemuel Haywood Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosarito Aninipot, Rosarito Aninipot Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosalyn D. Blumenthal, Rosalyn D. Blumenthal Search for other works by this author on: Oxford Academic PubMed Google Scholar David M. Goldenberg David M. Goldenberg * *Correspondenee to: David M. Goldenberg, ScD, MD, Garden State Cancer Center and Center for Molecular Medicine and Immunology, 1 Bruce St, Newark, NJ 07103 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 9, 1 May 1991, Pages 627–632, https://doi.org/10.1093/jnci/83.9.627 Published: 01 May 1991 Article history Received: 21 September 1990 Received: 11 February 1991 Accepted: 20 February 1991 Published: 01 May 1991
Clinical outcomes of obese low socioeconomic status women diagnosed with invasive breast cancer.
Authors: DR Quispe, ME Quispe, S Runhua, SW Amanda, BV Gary
Journal: Cancer Research (2009)

Abstract Abstract #6092 Background: Obesity a possible risk factor for breast cancer development, may along with low socioeconomic status (LSES) influence breast cancer outcomes. Louisiana a state with the second highest level of poverty has an obesity prevalence above 25%. The Feist-Weiller Cancer Center (FWCC) provides oncology care to the majority of LSES patients (pts) in the nothern half of the state. This study examines if there is a difference in clinical outcomes in obese patients with invasive breast cancer treated at FWCC.&amp;#x2028; Methods: The electronic medical records of pts with histologically proven invasive breast cancer diagnosed between 1981-2006 at FWCC were reviewed. Pts with Stage IV breast cancer at diagnosis were excluded. Data on insurance, race, body mass index at diagnosis (BMI), stage, disease free interval (DFI) and survival time was analyzed. National Institutes of Health criteria was used to stratify pts into normal weight (NW)[ BMI &amp;lt;25 kg/m2], overweight (OW) [BMI 25-30 kg/m2], and obese (OB)[BMI &amp;gt;30 kg/m2]. LSES was defined as pts who were either uninsured or received Medicaid assistance. Differences in DFI and Overall survival (OS) were analyzed by BMI.&amp;#x2028; Results: 647 pts were analyzed, 49% were obese and 29% were overweight. 47% were African Americans and 53% were Caucasians. 49% had LSES (22% uninsured and 27% received Medicaid). Obese pts were more likely to be African American (58%; p&amp;lt;0.001), LSES (57%; p=0.003), with Stage III breast cancer at diagnosis (23%; p=0.003) and to develop contralateral breast cancer after the initial diagnosis (10%; p=0.003). One hundred seventy three (27%) pts relapsed (90 obese and 82 non obese) and 74 (11%) deaths occurred (37 obese and 40 non obese). Obese pts had a shorter median DFI (56 months) in comparison with NW and OW pts (67 months and 70 months, respectively) however this difference was not statistically significant (p=0.43). Regarding OS, there were no statistically significant differences between BMI groups. In multivariate analysis using Cox regression model, after adjusting for race, SES, stage at diagnosis, menopausal status, age at diagnosis, smoker status, obesity remains as a none significant predictor of time to relapse. (HR=1.3; p=0.12)&amp;#x2028; Conclusion: Our results suggest that African American race, low socioeconomic status, stage III at diagnosis and contralateral breast cancer occurrence are associated with obesity at diagnosis of invasive breast cancer. In our patient population, obesity did not appear to contribute to increase risk of relapse or shorter OS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6092.
Abstract 4114: Trimeric G protein-CARMA1 axis links smoothened to NF-κB activation in diffuse large B-cell lymphoma.
Authors: Changju Qu, Yadong Liu, Kranthi Kunkalla, Rajesh Singh, Marzenna Blonska, Nitin Agarwal, Xin Lin, Francisco Vega
Journal: Cancer Research (2013)

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and NF-κB pathways is ubiquitously observed and known to mediate tumor growth, survival and chemo-resistance in DLBCL. Previously, we found that activation of Hh signaling is positively correlated with NF-κB pathway in DLBCL tumors and that modulating the activity of smoothened (SMO), the signal transducer subunit of Hh pathway, but not GLI1, transcriptional factor of Hh signaling, resulted in modulation of NF-kB pathway activation. Hereby, we investigate the molecular mechanisms that link SMO to NF-kB pathway. To elucidate whether there was interaction between G protein superfamily and SMO, we immunoprecipitated representative members of the Gα subfamilies (Gαi, Gα16, Gαq, Gαs and Gα12), and found that SMO was associated with Gαi, Gαq, and Gα12 in two DLBCL cell lines. Stimulation of SMO with Shh recombinant increased the recruitment of Gαi and Gα12 to SMO and also increased the GTPase activity of Gαi and Gα12. We also found that the activation of SMO with Shh in DLBCL cell lines was associated with increased total activity of PKC, phosphorylation of PKCβ1 and -2, and recruitment of CARMA1-MALT1-BCL10-TRAF6 to SMO receptor complex supporting that G proteins are involved in the transmission of the signal between SMO and NF-κB. Opposite results were seen when SMO was inhibited or silenced. As polyubiquitination of TRAF6 and NEMO (IKKγ) at lysine 63 (K63) are also important events in propagating NF-κB signaling, we examined the effect of SMO overexpression on K63-linked polyubiquitination of TRAF6 and NEMO. Transient overexpressing SMO resulted in increased polyubiquitination of TRAF6 and NEMO, supporting activation of both proteins by SMO. Moreover, functional inhibition of SMO (cyclopamine-KAAD) enhances the cytotoxic effect of NF-κB inhibitor (BAY-11-7082). Altogether, our study reveal a non-canonical Hh signaling pathway, in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-κB activation. This signaling cascade contributes to the survival of DLBCL, and may serve as potential targets for combination therapies in DLBCL. Citation Format: Changju Qu, Yadong Liu, Kranthi Kunkalla, Rajesh Singh, Marzenna Blonska, Nitin Agarwal, Xin Lin, Francisco Vega. Trimeric G protein-CARMA1 axis links smoothened to NF-κB activation in diffuse large B-cell lymphoma. [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 4114. doi:10.1158/1538-7445.AM2013-4114
Effect of Exercise on the Peripheral Utilization of Glucose in Man
Authors: Charles A. Sanders, Gilbert E. Levinson, Walter H. Abelmann, Norbert Freinkel
Journal: New England Journal of Medicine (1964)

THE occasional hypoglycemia in marathon runners and the enhanced glucose tolerance and amelioration of diabetes mellitus that may occur during physical effort have long afforded evidence that exercise can alter glucose homeostasis in man.1 2 3 4 5 6 Indeed, vigorous exercise constituted one of the main forms of therapy in the preinsulin era.1 , 2 Conceivably, the blood-sugar-lowering actions of exercise could be ascribed to suppression of hepatic glucose output or enhanced peripheral glucose utilization or both. As yet, experimental data to differentiate these possibilities have not been forthcoming in man. In contrast, information obtained in laboratory animals7 8 9 10 11 12 13 has shown augmented production of C14-labeled carbon . . .
Mind-Body Meld May Boost Immunity
Authors: J. Flach, L. Seachrist
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Mind-Body Meld May Boost Immunity Get access Jennifer Flach, Jennifer Flach Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa Seachrist Lisa Seachrist Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 4, 16 February 1994, Pages 256–258, https://doi.org/10.1093/jnci/86.4.256 Published: 16 February 1994
A7.13 Distinct expression of IL-36α, β, γ and their antagonists IL-36RA and IL-38 in psoriasis, rheumatoid arthritis (RA) and crohn’s disease (CD)
Authors: MA Boutet, G Bart, M Gahier, J Amiaud, B Brulin, C Charrier, F Morel, J-C Lecron, M Rolli-Derkinderen, A Boureille, S Vigne, C Gabay, G Palmer, B Le Goff, F Blanchard
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The IL-36 family of cytokines comprises three agonists: IL-36α, IL-36β and IL-36γ, an antagonist: IL-36Ra, and IL-38: another potential IL-36 inhibitor. IL-36 agonists are highly expressed in skin and are involved in the pathogenesis of psoriasis, while antagonists limit uncontrolled inflammation. The expression and role of IL-36 cytokines in other chronic inflammatory diseases is currently debated. In this study, we compared the expression profile of IL-36 cytokines in psoriasis, RA and CD. <h3>Materials and methods</h3> Skin, joint and colon inflammation was induced in mice. Skin, synovial and colonic biopsies from patients respectively with psoriasis, RA or CD were collected. Synovial fluids from patients with RA were also collected. These samples were analysed for cytokines expression by RT-qPCR, ELISA, immunohistochemistry and confocal microscopy. The cell sources of IL-36 cytokines were confirmed in cell cultures after stimulation with inflammatory cytokines and TLR agonists by RT-qPCR. <h3>Results</h3> During imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36β and IL-38, was induced and correlated with Th17 cytokines (IL-17A, IL-22…). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, β, γ, IL-36Ra and IL-38 were all elevated and correlated with myeloid cytokines such as CCL3, CCL4 and MCSF, but not with Th17 cytokines. In mice with dextran sulfate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at a relatively low level. Only a minor subgroup of patients with RA (17–29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By IHC and in cell cultures, the different IL-36 cytokines were produced at different levels by human keratinocytes, CD68<sup>+</sup> inflammatory macrophages, dendritic/Langerhans cells, and CD79α<sup>+</sup> plasmocytes. <h3>Conclusion</h3> Expression of the different IL-36 cytokines is differently regulated and their cell sources are distinct. This helps to explain the different expression profiles observed in three chronic inflammatory diseases and why only a minor subgroup of RA and CD patients have an elevated IL-36 agonists/antagonists ratio. Additional studies are necessary to better identify these patients and to investigate whether they would benefit from IL-36 neutralisation.
HLA-DR Specificities among Black Americans with Juvenile-Onset Diabetes
Authors: Glenn E. Rodey, Neil White, Teresa E. Frazer, Rene J. Duquesnoy, Julio V. Santiago
Journal: New England Journal of Medicine (1979)

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.
Abstract B42: Structure-activity study of tubulin precipitation by thiol-reactive compounds
Authors: Lixin Mi, Fung-Lung Chung
Journal: Cancer Research (2011)

Abstract Tubulin, a major constituent of microtubules, has been established as an important chemotherapeutic target. Its expression is tightly regulated at the transcriptional level and not affected by tubulin targeting agents including taxanes and vinca alkaloids. Recently, we reported that benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC), two isothiocyanates (ITCs) derived from cruciferous vegetables, induce rapid and significant precipitation and degradation of both α- and β-, but not γ-, tubulin at 10 μM through covalent binding to cysteine residues. In contrast, sulforaphane and erucin, two hydrophilic ITCs, and N-methylphenethylamine, an analog of PEITC without electrophilic functional group, show no activity as well as little downstream effects such as cell cycle arrest at mitosis and apoptosis induction at the same concentration. Because ITC are electrophiles, these findings suggest that thiol-reactivity may be the triggering event, the structure of compounds is associated with its activity, and tubulin precipitation and degradation are biologically important. In this study, we report that other thiol-reactive compounds, such as N-benzylmaleimide, phenylarsine oxide, and phenylmercuric chloride, also induce significant tubulin precipitation. They were much more potent than their hydrophilic counterparts, such as N-maleoyl-beta-alanine, arsenic oxide, and mercury chloride. These results shed lights onto structure-activity relationships. More importantly, their potencies of precipitating tubulin correlate well with not only their affinity to tubulin cysteines but also induction of G2/M phase arrest and apoptosis in human lung cancer cells A549. The results support the notion that cysteine modification is an upstream event for tubulin instability and cytotoxicity. The study presents critical knowledge on the rational design and screening of thiol-reactive compounds targeting the stability of tubulin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B42.
Subcutaneous Implantation Type Central Veins Port (CV Port) Management in Patients with Malignant Tumor
Authors: J. Sato, M. Kumagai, K. Kato, A. Akahane, M. Suzuki, S. Ehara, M. Sone, K. Takahashi, K. Kudo
Journal: Annals of Oncology (2013)
Abstract 200: EGCG inhibits pancreatic cancer stem cell characteristics in human primary tumors, and carcinogenesis in KrasG12D transgenic mice.
Authors: Luke Marsh, Su-Ni Tang, Dara Nall, Chris Jackman, Sharmila Shankar, Rakesh K. Srivastava
Journal: Cancer Research (2013)

Abstract EGCG, a component of green tea, exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines through diverse mechanisms. However, the mechanisms by which EGCG inhibits cell proliferation and induces apoptosis are poorly understood. The objectives of this study were to examine the molecular mechanisms by which EGCG inhibits stem cell characteristics of pancreatic cancer stem cells (CSCs) derived from human primary tumors and carcinogenesis in KrasG12D transgenic mice. Human pancreatic CSCs (CD133+CD44+CD24+ESA+) are highly tumorigenic and form subcutaneous tumors in NOD/SCID IL2R gamma mice. Human pancreatic CSCs expressing high levels of CD133, CD24, CD44, ESA, and aldehyde dehydrogenase also express significantly more Nanog, Oct-4, Notch1, MDR1 and ABCG2 than normal pancreatic tissues and primary pancreatic cancer cells. Similarly, CSCs from KrasG12D mice express significantly high levels of pluripotency maintaining factors than pancreatic tissues from Pdx-Cre mice. EGCG inhibits the growth (size and weight) and development (PanIN lesions) of pancreatic cancer in KrasG12D mice by suppressing the activation of Kras, ERK, AKT and FoxO. EGCG inhibits the self-renewal capacity of pancreatic CSCs derived from human primary tumors and KrasG12D mice. EGCG inhibits pluripotency maintaining factors (Nanog, Sox-2, c-Myc and Oct-4) and drug resistance gene ABCG2 in CSCs. Inhibition of Nanog by shRNA enhances the inhibitory effects of EGCG on self-renewal capacity of CSCs. Finally, EGCG inhibits CSC's migration and invasion and markers of epithelial-mesenchymal transition (Zeb-1, Slug and Snail). These data suggest that EGCG can inhibit pancreatic cancer development in human and KrasG12D transgenic mice by inhibiting stem cell characteristics. In conclusion, EGCG can be used for the management of pancreatic cancer. Citation Format: Luke Marsh, Su-Ni Tang, Dara Nall, Chris Jackman, Sharmila Shankar, Rakesh K. Srivastava. EGCG inhibits pancreatic cancer stem cell characteristics in human primary tumors, and carcinogenesis in KrasG12D transgenic mice. [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 200. doi:10.1158/1538-7445.AM2013-200
Local Toxicity of Piroxantrone: An Anthrapyrazole With Irritant and Vesicant Properties Similar to Those of Doxorubicin
Authors: B. V. CLARKE, K. V. HARWOOD, R. DONEHOWER
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Local Toxicity of Piroxantrone: An Anthrapyrazole With Irritant and Vesicant Properties Similar to Those of Doxorubicin Get access BARBARA VITO CLARKE, BARBARA VITO CLARKE * The Johns Hopkins Oncology CenterBaltimore, MD *Correspondence to: Barbara Vito Clarke, The Johns Hopkins Oncology Center, 600 N. Wolfe St., Baltimore, MD 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar KERRY V. HARWOOD, KERRY V. HARWOOD The Johns Hopkins Oncology CenterBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar ROSS DONEHOWER ROSS DONEHOWER The Johns Hopkins Oncology CenterBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 17, 6 September 1989, Pages 1331–1332, https://doi.org/10.1093/jnci/81.17.1331 Published: 06 September 1989
Expression of Endothelin-1 in the Lungs of Patients with Pulmonary Hypertension
Authors: Adel Giaid, Masashi Yanagisawa, David Langleben, Rene P. Michel, Robert Levy, Hani Shennib, Sadao Kimura, Tomoh Masaki, William P. Duguid, Duncan J. Stewart
Journal: New England Journal of Medicine (1993)

Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension.