tbuckley/cabot-search huggingface dataset:
Abstract 4956: Pharmacological inhibition of Bruton's Tyrosine Kinase (BTK) as a therapy for insulinoma and pancreatic ductal adenocarcinoma.
Authors: Daniel Massó-Vallés, Erika Serrano, Jonathan R. Whitfield, Joseph J. Buggy, Nicole M. Sodir, Nesrine I. Affara, Lamorna Brown Swigart, Gerard I. Evan, Laura Soucek
Journal: Cancer Research (2013)

Abstract Myc, a pleiotropic transcription factor that is deregulated and/or over-expressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis and inflammation. We previously showed in a model of pancreatic [[Unsupported Character - Symbol Font β]] cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. Moreover, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. While this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans and no other systemic inhibitor of mast cell degranulation has hitherto been available. Ibrutinib is a novel inhibitor of Bruton's tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trials as a therapy for B cell non-Hodgkin's lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with Ibrutinib efficiently inhibits Btk, blocks mast cell degranulation and triggers collapse of tumor vasculature and tumor regression. We also show that pancreatic ductal adenocarcinoma (PDAC)-bearing mice treated with Ibrutinib survive longer and present reduced tumor stroma, suggesting that combinatorial therapy with Ibrutinib and standard of care is a feasible therapeutic approach. Conclusions: our data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor Ibrutinib may be useful in treating pancreatic cancer. Citation Format: Daniel Massó-Vallés, Erika Serrano, Jonathan R. Whitfield, Joseph J. Buggy, Nicole M. Sodir, Nesrine I. Affara, Lamorna Brown Swigart, Gerard I. Evan, Laura Soucek. Pharmacological inhibition of Bruton's Tyrosine Kinase (BTK) as a therapy for insulinoma and pancreatic ductal adenocarcinoma. [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 4956. doi:10.1158/1538-7445.AM2013-4956
Selecting the right drug treatment for adults with type 2 diabetes
Authors: Victor M Montori
Journal: BMJ (2016)

We need to turn uninformed choice into random allocation

Clinicians prescribe one or more antihyperglycaemic drugs to prevent and treat symptomatic hyperglycaemia and to lower haemoglobin A1c levels in people with type 2 diabetes. The available agents differ in their efficacy and safety and in how they burden patients in terms of dosing, side effects, and cost. Comparative estimates across these outcomes are generally lacking, limiting the ability of patients and clinicians to make informed decisions.

Reasonably, these estimates may be obtained from data generated in the process of caring for patients. Two observational studies in this issue are based on data acquired during the routine care of people with type 2 diabetes in the United Kingdom. One of the studies, by Hippisley-Cox and Coupland (doi:10.1136/bmj.i1450), compares antihyperglycaemic drugs, particularly gliptins and glitazones, in their ability to control hyperglycaemia, induce hypoglycaemia, and prevent blindness, amputations, and renal failure.1 The other study, by Tuccori and colleagues (doi:10.1136/bmj.i1541), focuses on the association between pioglitazone and bladder cancer.2

These authors took advantage of practice based databases that include most people with type 2 …
Abstract P5-07-01: Defining the mechanism of breast cancer growth by chemokine receptor CXCR7 and Epidermal Growth Factor Receptor coupling interaction.
Authors: N Salazar, D Muñoz, RK Singh, BL Lokeshwar
Journal: Cancer Research (2012)

Abstract Introduction: Breast cancer (BrCa) ranks second in both incidence and cancer deaths for women in the USA. Recent advances have revealed a significant contribution of chemokines and their receptors in tumor growth, survival after chemotherapy, and organ-specific metastasis. CXCR7 is the latest CXC-chemokine receptor implicated in BrCa growth. It is endogenously over expressed in BrCa, but its mechanism of tumor growth enhancement is still not clearly defined. CXCR7 heterodimerizes with CXCR4 and binds to SDF-1 (CXCL12) and CXCL11. No direct ligand mediated physiological action has been implicated for CXCR7 in BrCa other than facilitating CXCR4-mediated cell motility, however, studies in other cancers have implicated CXCR7 in cell proliferation, anti-apoptotic activity and cell-cell adhesion. The expression pattern of CXCR7 in BrCa tissues and its potential contribution in BrCa cell proliferation and survival were investigated in representative BrCa cell lines using knock down and knock-in experiments. Results: CXCR7 was only expressed in ER-α positive BrCa cells (e.g., MCF-7) and was not found in BrCa cells with known metastatic potential (MDA-MB231 and SKBr3). Depletion of CXCR7 in MCF-7 BrCa cells by both siRNA and shRNA decreased cell proliferation and caused cell cycle arrest. Since CXCR7 is an atypical G-protein coupled receptor where ligand activation does not elicit conventional intracellular signaling, we hypothesized that CXCR7 regulates BrCa proliferation through interaction with EGFR or activating other potential targets of MAP-kinase activation. CXCR7 depletion reduced site-specific phosphorylation of EGFR at Tyrosine 1110 after EGF-stimulation. CXCR7 depletion also reduced phosphorylation of ERK-1/2, indicating a potentially direct interaction with mitogenic signaling in MCF-7 cells. We tested for direct interaction of CXCR7 with EGFR by co-immunoprecipitation and immunofluorescence studies. We found EGFR and CXCR7 co-immunoprecipitate and co-localize as demonstrated by confocal microscopy. Interestingly, our results also demonstrate CXCR7 and EGFR are co-localized before EGF stimulation. Further corroboration of CXCR7-EGFR interaction was established using the proximity ligation assay (PLA) technique that allowed us to visualize CXCR7-EGFR co-localization both in cell culture and in human normal and breast cancer tissue. Conclusion: This data demonstrates an important role for CXCR7 in BrCa growth and explores the mechanism of action of direct coupling of EGFR with CXCR7. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-07-01.
P641Dependence of the cardiac connexins Cx43:Cx45 ratio on the formation of gap junction channels and their electrical properties
Authors: S Dupuis, S Chaigne, M Constantin, T Desplantez
Journal: Cardiovascular Research (2014)

The cardiac action potential (AP) propagation is regulated to permit the coordinated and rhythmic atrial and ventricular contractions. This regulation requires passive and active factors. A key factor is the gap junctions, which ensure a direct pathway for electrical and biochemical signaling. They are clusters of intercellular gap junction channels (GJC) made of two hemichannels docked in the membrane of adjacent cells, which are composed of six connexins (Cxs). Their distinct electrical properties are considered as a key factor regulating the propagation of the AP. Four cardiac Cxs, Cx40, Cx43, Cx45 and Cx30.2, exhibit specific patterns of expression that change in the healthy and diseased heart, which leads to different possible configurations of GJC in term of organization and Cxs composition. The aim of this study is to investigate the function of the distinct ratio of co-expressed Cx43:Cx45 in regulating the formation and the function of GJC. Rat Liver Epithelial cells stably transfected to induce accurate Cx43:Cx45 ratios of 0 (single Cx43 expression), 0.5, 1 and 2 are used. Electrical properties of GJC (i.e. junctional coupling, voltage dependence, unitary conductance) are determined by performing electrical recordings on cell pair by applying the dual voltage-clamp method. The ongoing recordings show distinct electrical properties before and after the induction of Cx45: induction of Cx45 decreases the cell-to-cell coupling, lowers and rectifies the voltage dependence of GJC. Preliminary unitary recordings suggest a distinct formation of GJC of mixed Cx43 and Cx45 composition in function of the specific Cx43:Cx45 ratio. Further investigations will provide better understanding on the distinct contributions of Cx43 and Cx45 in the GJC make-up, electrical properties and function of the Cx43/Cx45 expression pattern in regulating the cardiac impulse propagation in the healthy heart, and the pro-arrhythmic behavior of Cxs dysfunction and remodeling in the diseased heart.
Abstract 841: Inhibition of head and neck squamous cell carcinoma growth by combination treatment of erlotinib and celecoxib: Potential chemopreventive agents
Authors: Hongzheng Zhang, Sreenivas Nannapaneni, Zhengjia Chen, Nabil Saba, Fadlo R. Khuri, Georgia (Zhuo) Chen, Dong M. Shin
Journal: Cancer Research (2011)

Abstract The interaction of epithelial growth factor receptor (EGFR) and cyclooxygenase 2 (COX-2) pathways plays an important role in tumorigenesis. Our recent Phase I chemoprevention trial of premalignant lesions including pathologically moderate or severe dysplasia and carcinoma in situ in oral cavity and larynx showed a 71% (5/7) estimated overall response rate after a 6-month-long combination treatment of Erlotinib and Celecoxib without significant toxicities (ASCO 2010 Abstract # 5535). The current preclinical study was designed to investigate the underlying mechanisms that contribute to the inhibitory effect on the disease progression by the combined treatment of Erlotinib and Celecoxib. Chemopreventive efficacy was determined using a head neck squamous cell carcinoma (HNSCC) xenograft model with Tu212 cell line. Animals received vehicle control (0.1% Tween 80 and 0.5% methylcellulose, n=6), Celecoxib at 50mg/kg body weight (n=6), Erlotinib at 75mg/kg body weight (n=7), or combination of Erlotinib and Celecoxib (n=8) with the same dose as the single agent by oral gavaging daily for 6 days before subcutaneous implantation of cancer cells. Animals were further treated daily for 5 days per week with a total of 4 weeks. The combination treatment significantly suppressed tumor growth compared with Erlotinib alone (p=0.01), Celecoxib alone (p&amp;lt;0.0001) or the vehicle control (p&amp;lt;0.0001). In vitro study was performed with Tu212 and Tu686 HNSCC cell lines. Cell cycle analysis revealed that G1 arrest was induced by either Erlotinib alone (59% and 67% for Tu212 and Tu686, respectively), or Celecoxib alone (50% and 58% for Tu212 and Tu686 cells, respectively). The combination treatment resulted in greater G1 arrest than either single agent alone (72% in Tu212 and 65% in Tu686 cells). Molecular analysis showed that the combined treatment augmented suppression of pERK, pAKT and pEGFR. In addition, Erlotinib suppressed mTOR pathway by diminishing pS6. These results support the findings in the phase I study. The study has progressed to Phase II clinical trial. In conclusion, augmented inhibition of pEGFR/pERK/pS6 pathways could contribute to the synergism by Erlotinib and Celecoxib in suppressing HNSCC tumor growth. (This study is supported by NIH grant U01 CA151802 and P50CA128613 to Dr. Shin and Georgia Cancer Coalition Distinguished Cancer Scholar award to Drs Shin and Chen. *: These authors had equal contribution.) 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 841. doi:10.1158/1538-7445.AM2011-841
Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial
Authors: Olivier Mir, Claire Cropet, Maud Toulmonde, Axel Le Cesne, Mathieu Molimard, Emmanuelle Bompas, Philippe Cassier, Isabelle Ray-Coquard, Maria Rios, Antoine Adenis, Antoine Italiano, Olivier Bouché, Emmanuelle Chauzit, Florence Duffaud, François Bertucci, Nicolas Isambert, Julien Gautier, Jean-Yves Blay, David Pérol
Journal: The Lancet Oncology (2016)
Abstract 4399: In vitro and in vivo evaluations of correlation between the activation status of signaling pathways and the efficacy of anticancer compounds in a panel of JFCR39 human cancer cell lines
Authors: Shingo Dan, Mutsumi Okamura, Mariko Seki, Kanami Yamazaki, Yumiko Mukai, Takao Yamori
Journal: Cancer Research (2011)

Abstract The phosphoinositide 3-kinase (PI3K) pathway and the Ras/mitogen-activated protein kinase (MAPK) pathway are frequently activated in cancer. Activation of these pathways contribute to cell survival, cell cycle progression and cell growth in the tumor, and are expected to influence the efficacy of antitumor compounds including conventional antitumor drugs, PI3K pathway inhibitors and Ras/MAPK pathway inhibitors. However, it is not well understood whether the efficacies of anticancer compounds can be predicted based on these aberrations and on the activation status of signaling pathway members. To clarify this issue, we first examined the mutation, expression and phosphorylation status of PI3K and Ras/MAPK pathway members in a panel of 39 pharmacologically well-characterized human cancer cell lines (JFCR39). Second, we evaluated the in vitro efficacy of various anticancer compounds including PI3K and Ras/MAPK pathway inhibitors and conventional anticancer drugs, combining these data to construct an integrated database of pathway activation status and drug efficacies (JFCR39-DB). In silico analysis of JFCR39-DB enabled us to evaluate correlations between the status of pathway members and the drug efficacies in vitro. For example, KRAS/BRAF mutation prominently correlated with the efficacy of a MEK inhibitor and the inefficacy of PI3K inhibitors, respectively, while phosphorylation levels of Akt correlated with the efficacy of PI3K inhibitors. Some of these correlations were confirmed in human tumor xenografts in vivo, consistent with their ability to serve as predictive biomarkers. Our findings show that JFCR39-DB is a useful tool to identify predictive biomarkers and to study molecular pharmacology of the PI3K and Ras/MAPK pathways in cancer therapy. 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 4399. doi:10.1158/1538-7445.AM2011-4399
Levamisole and Fluorouracil for Adjuvant Therapy of Resected Colon Carcinoma
Authors: Charles G. Moertel, Thomas R. Fleming, John S. Macdonald, Daniel G. Haller, John A. Laurie, Phyllis J. Goodman, James S. Ungerleider, William A. Emerson, Douglas C. Tormey, John H. Glick, Michael H. Veeder, James A. Mailliard
Journal: New England Journal of Medicine (1990)

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2).
Case 7-1999
Authors: Sapna Syngal, Stamatina Kaptain
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 50-year-old woman was admitted to the hospital because of diarrhea that had developed during radiation treatment.The patient had been well until 15 years earlier, when a stage 1A, Clark level II malignant melanoma (Figure 1), 0.45 mm in thickness, was excised from her back. Six months before admission, a mammographic examination showed a left axillary mass. A biopsy of the mass performed 21 weeks before admission showed metastatic melanoma. Ten days later, a computed tomographic (CT) scan of the chest showed multiple enlarged axillary lymph nodes and minimal pericardial fluid or thickening. An abdominal CT . . .
SAT0051 Vitamin D Levels and Inflammation in the Aortic Wall of Patients with Inflammatory Rheumatic Disease and Coronary Artery Disease
Authors: I. Oma, T. Lyberg, J. K. Andersen, Ø. Molberg, J. E. Whist, I. L. Kvelstad, T. Veel, M. W. Fagerland, S. M. Almdahl, K. Mikkelsen, I. Hollan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vitamin D is involved in immune reactions, and vitamin D deficiency is associated with autoimmune diseases and with cardiovascular diseases (CVDs). In Feiring Heart Biopsy Study (FHBS), we previously demonstrated a high occurrence of mononuclear cell infiltrates (MCIs) in subintimal layers of the aorta, related to inflammatory rheumatic disease (IRD). In theory, vitamin D deficiency might contribute to vascular inflammation involved in the pathogenesis of CVD along with the accelerated CVD in IRD. <h3>Objectives</h3> To look for differences in plasma levels of 25(OH)D<sub>3</sub> and 1,25(OH)<sub>2</sub>D<sub>3</sub> in patients with coronary artery disease (CAD) with and without IRD. To search for relationships between inflammation in subintimal aortic layers (in terms of MCIs) and plasma levels of 25(OH)D<sub>3</sub> and 1,25(OH)<sub>2</sub>D<sub>3</sub>. <h3>Methods</h3> Plasma levels of 25(OH)D<sub>3</sub> were examined by radioimmunoassay and 1,25(OH)<sub>2</sub>D<sub>3</sub> by immunoassay in 53 patients with CAD and 68 patients with CAD and IRD from FHBS. The D vitamin levels were then related to the number of MCI previously identified in the subintimal aortic layers of these patients<sup>1</sup>. <h3>Results</h3> In crude analysis, we observed no significant differences in 25(OH)D<sub>3</sub> and 1,25(OH)<sub>2</sub>D<sub>3</sub> levels between patients with CAD and IRD and patients with CAD only (see Table). Nor did we observe any significant crude associations between vitamin D levels and occurrence of MCIs in the subintimal aortic layers. However, after adjustment for age, sex, CRP, glucocorticosteroids, daily vitamin and mineral supplementation, and IRD status, patients with MCIs in the subintimal aortic layers had lower levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> than patients without (inter-group difference = 17.0 pmol/l (95%CI: 2.8 to 31.3), p=0.019). <h3>Conclusions</h3> Our study does not support the hypothesis that patients with CVD and IRD have lower levels of vitamin D than patients with CVD only. Interestingly, based on multivariate analyses, low 1,25(OH)<sub>2</sub>D<sub>3</sub> levels were associated with subintimal aortic inflammation. This finding should be explored in future studies. If a causal relationship exists, vitamin D supplementation could reduce vascular inflammation and thereby have potential therapeutic effect in CVD. <h3>References</h3> I. Hollan <i>et al</i>., <i>Arthritis Rheum,</i> 56 (2007), 2072-9. <h3>Disclosure of Interest</h3> None Declared
Abstract 195: Functional epigenetics identifies a protein phosphatase-1 regulatory subunit gene as a candidate tumor suppressor frequently silenced by promoter CpG methylation in multiple tumors
Authors: Ching Hei Leung, Ka Man Ng, Ada Ho Yan Wong, Jian ming Ying, Gopesh Srivastava, Sing Fai Leung, Anthony Tak Cheung Chan, Qian Tao
Journal: Cancer Research (2010)

Abstract Protein Phosphatase 1 regulatory subunits (PPP1R) are a family of small molecules which modify the function and protein targeting of protein phosphatase-1 upon their interactions. Deregulated expression of PPP1R members could often be found in cancer cells. For example, ASPP family is well known for its necessity of p53 function while ASPP silencing leads to carcinogenesis or poor prognosis in cancer patients. Here, one of the PPP1R members (TUSC7) was identified which its role in tumor suppression had been investigated Using semi-quantitative RT-PCR, expression profile of TUSC7 in cancer cell lines was obtained. TUSC7 was frequently silenced in cancer cells. Bisulfite treated tumor DNA was subjected to Methylation-specific PCR (MSP) using primers flanking across the ∼130bp CpG island of the TUSC7 promoter. It was revealed that silencing of TUSC7 was due to promoter hypermethylation in most of the corresponding cancer cell lines which had been further confirmed by bisulfite genomic sequencing (BGS). Treatment with azacytidine and trichostatin restored TUSC7 expression through demethylating the hypermethylated promoter. To quantitatively determine the extensiveness of cancer cell growth inhibition by TUSC7, colony formation assay was used. It was found that ectopic expression of TUSC7 could inhibit the proliferation of tumor cells, Caski (cervical carcinoma), HCT116 (colon carcinoma) and KYSE150 (esophageal squamaus carcinoma cells) by 40-50%. In addition, ectopic expression of TUSC7 increased the amount of phosphorylated GSK-3beta (pSer9-GSK-3beta) as shown in the western blot analysis. pSer-9 GSK-3beta is the inactive form of GSK-3beta. It has been reported that inactive GSK-3beta may affect p53 activities. To summarize, TUSC7 was found to be a tumor suppressor frequently silenced in cancer cells through epigenetic mechanism. TUSC7 may be significant in regulating the activity of GSK-3beta whose signaling is important in carcinogenesis. 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 195.
Stat Bite: Trends in Bladder Cancer Incidence and Mortality, 1973-1989
Authors: B. F. Hankey
Journal: JNCI Journal of the National Cancer Institute (1992)

Stat Bite : Trends in Bladder Cancer Incidence and Mortality, 1973–1989 Get access Benjamin F. Hankey, Sc.D Benjamin F. Hankey, Sc.D Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 22, 18 November 1992, Page 1689, https://doi.org/10.1093/jnci/84.22.1689-a Published: 18 November 1992
OUTCOMES OF CORONARY SPASM PATIENTS WITH INTERMEDIATE RESPONSE TO ERGONOVINE ARE FAVORABLE AND SIMILAR TO THOSE WITH SEVERE VASOCONSTRICTION
Authors: Sang-Yong Yoo, Habib Samady, Spencer B. King III, Olivia Hung, Emad Rasoul Arzrumly, Sangsig Cheong, Dae-Hee Shin, Lee Changkun, Jin-Woo Kim, Gwan-Heop Sohn, Sung-Gyun Ahn
Journal: Journal of the American College of Cardiology (2015)
Endoscopic Ultrasonography in Determinating Invasion Depth of Rectal And Anus Tumors
Authors: V Nemudrov, L Mitina
Journal: Endoscopy (2006)

Introduction: Anal tumor is relatively rare type of cancer that is often disguising itself for some other rectal diseases because of non-specific symptoms. Other disease may also coexist with tumor. The main diagnostic methods of the rectal tumors are visual examination and digital rectal investigation. US examination may be considered as a method for making the diagnosis more precise.