tbuckley/cabot-search huggingface dataset:
Abstract 1625: Crosstalk between breast cancer and stromal cells occurs via exosomes and gap junctions in bone metastatic breast cancer.
Authors: Karen M. Bussard, Frank C. Marini
Journal: Cancer Research (2013)

Abstract Breast cancer preferentially metastasizes to the bone, where the five-year relative survival rate falls from 90% to &amp;lt;10%. Although the precise mechanism underlying preferential metastasis is unknown, the bone likely provides a hospitable environment that both attracts breast cancer cells and allows them to colonize and grow. Besides affects osteoblast and osteoclast properties, we have evidence that metastatic breast cancer cells further create a unique bone niche by orchestrating extensive crosstalk with osteoblasts that may be involved in creating a niche permissive for breast cancer cell dormancy. MC3T3-E1 murine osteoblasts were grown to confluence, then MDA-MB-231 human breast cancer cells added at a ratio of 1 breast cancer cell to 10 osteoblasts. Co-cultures were subsequently fixed and stained for Cx43 expression. Next, MC3T3-E1 cells and MDA-MB-231 cells were grown to confluence. Culture supernatants were removed and processed through a series of ultra-centrifugation, purification, and concentration steps to purify for exosomes. Finally, MC3T3-E1 cells were grown to various stages of maturity: 4 (growth) and 10 days (early differentiation) and incubated with conditioned medium from human MDA-MB-231 cells. qPCR was used to assay for changes in osteoblast-derived inflammatory cytokine expression. Expression of the gap junction protein Cx43 was localized between breast cancer cells and osteoblasts. Both MC3T3-E1 and MDA-MB-231 cells expressed exosomes, which were visualized using a transmission electron microscope. Osteoblast-derived cytokines increased in the presence of MDA-MB-231 breast cancer cell conditioned medium included MCP-1 (CCL2), LIX (CXCL5), LIF, and NFATc2. Overall, these data suggest that suggest there is extensive crosstalk directly between osteoblasts and breast cancer cells, and that osteoblasts are an important source of cytokines in breast cancer bone metastasis. Thus, these findings implicate the bone microenvironment and cancer cell manipulation thereof in orchestrating metastatic tumor cell dormancy, colonization, and survival. Supported in part by the National Institutes of Health; 1RC1 CA146381, 1R01NS06994, P50 CA083639 for FCM; Ruth L. Kirschstein Institutional Research Service Award (NRSA) T32 CA079448 for KMB. Citation Format: Karen M. Bussard, Frank C. Marini. Crosstalk between breast cancer and stromal cells occurs via exosomes and gap junctions in bone metastatic breast cancer. [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 1625. doi:10.1158/1538-7445.AM2013-1625
Nab-paclitaxel or docetaxel as alternatives to conventional paclitaxel for the treatment of metastatic breast cancer (MBC): a cost utility analysis in five European countries
Authors: G. Dranitsaris, M. Lidgren, J. Lundkvist, R. E. Coleman
Journal: Journal of Clinical Oncology (2008)

6571 Background: In patients with MBC, a common practice in Europe is to offer first line docetaxel or paclitaxel. However, one important drawback in their use, particularly with docetaxel, is dose-limiting toxicity. An albumin-bound formulation (nab) of paclitaxel was recently developed to overcome the safety drawbacks of these agents and to improve efficacy. To provide economic data from the perspective of the European Union, a cost utility analysis comparing nab-paclitaxel to docetaxel, both as alternatives to paclitaxel was conducted for the United Kingdom, France, Germany, Italy and Spain. Methods: The clinical data were obtained from a meta analysis of randomized trials comparing either nab-paclitaxel (260 mg/m^2 q3wk) or docetaxel (100 mg/m^2 q3wk), to conventional solvent-based paclitaxel (175 mg/m&2 q3wk). Health care resource use for the delivery of chemotherapy was collected from a survey of European medical oncologists and from the cancer literature. Treatment preferences and utility estimates were obtained from interviewing 70 female oncology nurses from the UK and France. Results: Nab-paclitaxel had the most favourable safety profile characterized with the lowest incidence of grade III/IV neutropenia, febrile neutropenia, anemia, emesis and stomatitis. This translated to lower overall costs for managing the grade III/IV side effects of nab-paclitaxel relative to both docetaxel and paclitaxel (e.g. in France; 286€ vs. 966€ vs. 422€). Using the median number of cycles administered as reported in the randomized trials and the cost impact of grade III/IV toxicity in each country, the overall cost for nab-paclitaxel was higher than conventional paclitaxel, but comparable to docetaxel. Overall, 47 of 70 (67.1%) respondents selected nab-paclitaxel as their preferred choice. As an alternative to paclitaxel, the incremental cost per QALY gained was lower for nab-paclitaxel than docetaxel in three of five countries evaluated. Conclusions: Given its more favorable safety profile, improved efficacy and comparable overall cost, nab-paclitaxel can be considered a preferred option over docetaxel as first-line chemotherapy in MBC from the perspective of the European Union. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Oncology Abraxis Oncology Abraxis Oncology
THU0461-HPR Global assessment of disease by the patient in the new ACR/EULAR remission criteria: Why do not fulfil the remission?:
Authors: S. Sanchez, S. Iniesta, M.P. Lisbona, A. Pàmies, M. Almirall, J. Maymo, J. Carbonell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recently, new criteria has been described for assessing Rheumatoid Arthritis (RA) remission. However, in clinical practice, patients who may be in remission by these criteria (ACR/EULAR 2011), ofter fail to meet patient's global assessment (PtGA) scale of 0 to 10 with a value less than or equal to 1. <h3>Objectives</h3> To evaluate in patients with rheumatoid arthritis (RA), the reasons for non compliance with the new remission criteria ACR/EULAR due to a high PtGA and not related to the activity of the RA. <h3>Methods</h3> We included consecutively from April to December 2011 all patients with RA in remission for the composite index of activity, simplified disease activity index (SDAI) ≤3.3 and swollen joint count (SJC) ≤1, tender joint count (TJC) ≤1, C-reactive protein (CRP) ≤1 mg/dl but with PtGA &gt;1 cm. Demographic variables (date of birth, sex, educational level), disease (date of diagnosis of RA, presence of radiological erosions, serum levels of RF and ACPA), activity DAS28, VAS pain (0-10 cm), PtGA (0-10 cm), functional disability by HAQ, treatment (corticosteroids, DMARDs and/or tumor necrosis factor (anti-TNF), and comorbidity not associated with RA as possible causes of a PtGA&gt;1 cm. Data were analyzed with SPSS v.15. <h3>Results</h3> 55 patients (87.3% women) with a mean age of 57.8±12.7 years and a mean disease duration of 4.2±3.1 years were included. 60% were seropositive for rheumatoid factor (RF), 61.8% for Anti-citrullinated protein antibodies (ACPA) and 87.3% had radiographic erosions. 20% of patients had basic studiesand only 16.4% medium-high level. The mean HAQ was 0.483±0.387. 80% were treated with DMARDs (47.3% methotrexate), a 34.5% anti-TNF with or whithout DMARDs, 52.8% were taken corticosteroids (mean dose to prednisone equivalent of 2.1±2.2 mg per day). The mean DAS28 was 2.3±0.5, the pain VAS 3.6±1.8 cm and 3.7 ± PtGA was 1.2 cm. Acute phase reactants were both below normal level (ESR=16.5±14.7 (normal &lt;37 mm/h) and CRP=0.3±0.2 (normal &lt;0.8mg/dl). The reasons why patients considered to be in remission (new ACR/EULAR criteria) did not meet a PtGA ≤1 cm is shown in Table 1. <h3>Conclusions</h3> In our series, 65.5% of the patients on remission by other components if the new ACR/EULAR criteria, reported a PtGA &gt;1 cm due to a non-RA joint disease, osteoarthritis and soft tissue rheumatism being most prevalent disorders. The Rheumatology nurse should ensure proper completion of visual analog scales especially the PtGA in patients with RA as it is an important variable in the index of activity and remission of the disease. <h3>Disclosure of Interest</h3> None Declared
The Factor VIII Abnormality in Severe von Willebrand's Disease
Authors: Theodore S. Zimmerman, Charles F. Abildgaard, Dominique Meyer
Journal: New England Journal of Medicine (1979)

We attempted to characterize the small amounts of factor VIII-Related antigen detectable in the severe recessive form of von Willebrand's disease with newly developed radioimmunoprecipitin techniques and radiocrossed immunoelectrophoresis. Previous studies have failed to demonstrate factor VIII-Related antigen in most patients tested, even with the highly sensitive immunoradiometric assays. Using the newer techniques, we found antigen in the plasma of six of eight patients with severe von Willebrand's disease from different kindreds. Qualitative abnormalities of the trace quantities of factor VIII-Related antigen were demonstrated in five of the patients, with absence or relative decrease of the larger, less anodal forms. In addition, five distinct patterns were observed, each suggesting a different molecular abnormality. Heterozygous parents had normal to moderately decreased factor VIII-Related antigen, with normal crossed immunoelectrophoretic patterns. This study suggests that severe von Willebrand's disease is a heterogeneous syndrome with various underlying molecular defects. (N Engl J Med 301:1307–1310,1979)
Diffuse Radiocolloid Uptake in the Bone Marrow of Thoracolumbar Vertebrae Extending to the Skull, Upper Sternum, Clavicles, Long Bones, and the Lung Secondary to Lymphoma Infiltration of the Bone Marrow
Authors: WEI-JEN SHIH, SYLVIA MAGOUN, VICKIE STIPP, PHILIP A. De SIMON
Journal: Clinical Nuclear Medicine (1999)

A patient with large cell lymphoma, diagnosed by excisional biopsy of an axillary lymph node, underwent Tc-99m sulfur colloid liver-spleen scintigraphy because of increasing serum bilirubin and higher liver enzyme levels. In addition to massive hepatosplenomegaly, the images showed diffusely increased uptake in the lungs and bone marrow of the skull, spine, clavicles, and long bones. These findings may reflect the expansion of hematopoietic activity secondary to lymphoma cell infiltration of the bone marrow, which was shown by an iliac crest biopsy. Diffuse uptake of the lungs and massive hepatosplenomegaly may indicate extramedullary hematopoietic activity.
Life-Threatening Bullous Skin Eruptions During Interleukin-2 Therapy
Authors: M. R. Staunton, M. C. Scully, P. E. L. Boit, F. R. Aronson
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Life-Threatening Bullous Skin Eruptions During Interleukin-2 Therapy Get access Michele R. Staunton, Michele R. Staunton Department of Medicine, University of CaliforniaSan Francisco, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Megin C. Scully, Megin C. Scully Department of Dermatology, University of CaliforniaSan Francisco, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip E. Le Boit, Philip E. Le Boit Department of Dermatology amd Department of Pathology, University of CaliforniaSan Francisco, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick R. Aronson Frederick R. Aronson * Department of Medicine and Cancer Research Institute, University of CaliforniaSan Francisco, Calif * Correspondence to: Frederick R. Aronson. MD. Cancer Research Institute. University of California. San Francisco. CA 94143–0128. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 1, 2 January 1991, Pages 56–57, https://doi.org/10.1093/jnci/83.1.56 Published: 02 January 1991 Article history Received: 04 September 1990 Accepted: 12 October 1990 Published: 02 January 1991
Abstract 5510: Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex.
Authors: Shaowei Li, Ji-an Wang, Rajesh L. Thangapazham, Peter Klover, Joel Moss, Thomas N. Darling
Journal: Cancer Research (2013)

Abstract Pharmacological approaches for treating tumors in patients with tuberous sclerosis complex (TSC) are inadequate. Although mTORC1 inhibitors such as rapamycin represent a major new avenue for treatment, we and others have shown that rapamycin improves but does not eradicate TSC skin tumors. We tested the effects of tranilast, an antiallergic and antifibrotic drug with antiproliferative effects, on fibroblasts grown from angiofibromas, forehead plaques, periungual fibromas, and normal-appearing skin from 5 patients with TSC. Tumor cells showed loss of TSC2 expression and hyperactivation of the mTORC1 signaling pathway. Tranilast (5, 10, 20, 40 μM) inhibited the viability of TSC skin tumor cells from five patients in an MTT assay. These effects on cell viability appeared to be independent of mTORC1 activity, since tranilast did not inhibit phosphorylation of ribosomal protein S6. Four paired samples of RNA from tumor and normal cells, treated with or without tranilast, were studied using gene expression arrays, revealing that tranilast significantly altered the expression of at least 36 genes, of which 12 are involved in transcription. In a xenograft model in which dermal-epidermal constructs comprising normal human keratinocytes with either TSC angiofibroma cells or TSC normal fibroblasts from a TSC patient were grafted to nude mice (6-8 mice per group), tranilast treatment (300 mg/kg/day) reduced the number of skin tumor cells compared to vehicle control group (P&amp;lt; 0.05). Tranilast treatment did not block angiogenesis or lymphangiogenesis in the xenograft model. These results indicate that tranilast has antiproliferative effects independent of mTORC1 and suggest that tranilast may be useful as an adjunctive agent for the treatment of TSC skin tumors. Citation Format: Shaowei Li, Ji-an Wang, Rajesh L. Thangapazham, Peter Klover, Joel Moss, Thomas N. Darling. Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex. [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 5510. doi:10.1158/1538-7445.AM2013-5510
Reflex Peripheral Venoconstriction Induced by Carotid Occlusion
Authors: EDWIN W. SALZMAN
Journal: Circulation Research (1957)

The present investigation was designed to obtain additional evidence for the effect of carotid sinus reflexes on venous tone. It was found that occlusion of one or both common carotid arteries increases tension in a miniature balloon inserted into a peripheral vein. Deafferentation of the aortic arch by cervical vagotomy enhanced the venous response. The time course and magnitude of the venous reactions paralleled the increase in arterial pressure. It appears that the homeostatic increase in peripheral resistance as a result of reflex arteriolar constriction is complemented by a decrease in size of the peripheral venous reservoir.
Abstract SY05-02: Hedgehog/wnt feedback supports regenerative proliferation of epithelial stem cells in bladder
Authors: Philip A. Beachy
Journal: Cancer Research (2011)

Abstract Epithelial integrity in metazoan organs is maintained through the regulated proliferation and differentiation of organ-specific stem and progenitor cells. Although the epithelia of organs such as the intestine regenerate constantly and thus remain continuously proliferative, other organs, such as the mammalian urinary bladder, shift from near-quiescence to a highly proliferative state in response to epithelial injury caused by bacterial infection or chemical agents. The cellular and molecular mechanisms underlying this injury-induced mode of regenerative response are poorly defined. Here we show that proliferation within the bladder is regulated by signal feedback between basal cells of the urothelium and the stromal cells that underlie them. We demonstrate that these basal cells include stem cells capable of regenerating all cell types within the urothelium, and are marked by expression of the secreted protein signal, Sonic hedgehog (Shh). Upon injury, Shh expression in these basal cells increases and elicits increased stromal expression of Wnt protein signals, which in turn stimulate the proliferation of both urothelial and stromal cells. The heightened activity of this signal feedback circuit and the associated increase in cell proliferation appear to be required for restoration of urothelial function and, in the case of bacterial injury, may help clear and prevent further spread of infection. Our findings provide a model for injury-induced epithelial regeneration in endodermal organs, and may provide a basis for understanding the roles of signaling pathways in cancer growth and metastasis. 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 SY05-02. doi:10.1158/1538-7445.AM2011-SY05-02
SP0025 Neutrophil microparticles - what do they do?
Authors: M. Perretti
Journal: Annals of the Rheumatic Diseases (2013)

Microparticles (MPs) are small vesicles shed from the plasma membrane that retain unique markers and mediators of their parent cell, enabling them to exert independent functions. Elevated levels of circulating MPs are associated with a number of cardiovascular and inflammatory pathologies, yet the extent of their contribution remains uncertain. An intriguing notion is that MPs originating from different cell types or after different stimulation can exert deleterious or protective effects. Proteomic analysis of neutrophil-derived MP - generated from cells stimulated in two different settings - revealed &gt;400 hits of which only ∼50% were identical. Coupling proteomic to western blotting and flow cytometry analyses allowed us to identify Alpha-2-Macroglobulin (A2M) as a novel determinant of the CD66b+ MP fraction in plasma samples of patients suffering from Giant Cell Arteritis, Rheumatoid Arthritis and sepsis, with over double the levels measured in healthy control or osteoarthritis plasma (n=10-15; P&lt;0.01). An interesting dichotomy emerged from septic patients who survived the event and those who did not survive. A series of experimental investigations demonstrated that A2M/CD66b+ neutrophil-derived MP activated endothelial cells under flow, preserved neutrophil chemotactic receptors and, ultimately, afforded protection in a model of sepsis. In summary, the take-home-message of this work are that: i) neutrophil-derived MP are heterogenous in their nature, and could be generated in a stimulus-dependent fashion, to elicit a variety of biological functions; ii) plasma Alpha-2-Macroglobulin/CD66b+ MPs could become a novel biomarker for <i>systemic inflammation</i> in human pathologies and could be quantified to monitor progress and clinical management. <h3>Funding</h3> British Heart Foundation, Arthritis Research UK and The Wellcome Trust. <h3>Disclosure of Interest</h3> None Declared
Abstract 5232: Tyrosine kinase inhibitor, gefitinib targets ZAP-70 over expressing chronic lymphocytic leukemia cells
Authors: Spencer Gibson, WenYan Xiao, Ju Yoon Yoon, Edward Noh, Michelle Brown, James B. Johnston
Journal: Cancer Research (2012)

Abstract Most patients with chronic lymphocytic leukemia (CLL) initially respond to chemotherapy but relapse. There is a subset of CLL patients that have aggressive disease characterized by an over expression of the tyrosine kinase ZAP-70. These ZAP-70+ patients have a poorer survival and are more resistant to chemotherapy. The biological effects of ZAP-70 in CLL are believed to be related to its ability to enhance activation of Syk with subsequent triggering of down-stream modulators, such as ERK and AKT. Normally, Syk is activated by increased phosphorylation by Lyn, which is increased in CLL, or by activation of the B-cell receptor. Gefitinib is a tyrosine kinase inhibitor that is presently used to treat lung cancer. The drug inhibits epidermal growth factor receptor (EGFR) tyrosine kinase activity but has activity against &amp;gt;20 other kinase targets, including members of the Src family of kinases, such as Lyn and Syk. We thus evaluated the cytotoxic activity of gefitinib against primary CLL cells using the MTT assay. Gefitinib was cytotoxic to ZAP-70+ (≥20% cells positive) CLL samples (median IC50, ∼3.0 µM) while ZAP-70- patients failed to respond to gefitinib with a median IC50 of &amp;gt;15.0 µM. Jurkat cells, which are T cells that express high levels of ZAP-70, were more sensitive to gefitinib than B cell lines that did not express ZAP-70 (BJAB and NALM6). Further studies confirmed that gefitinib was inducing cell death through apoptosis. Gefitinib was also effective against ZAP-70+ CLL cells that were resistant to fludarabine and chlorambucil indicating a novel mechanism of action to standard chemotherapy. Enhanced apoptosis was observed in ZAP70+ CLL and Jurkat cells exposed to gefitinib and fludarabine or chlorambucil, but this was not observed in ZAP-70- or the B cell lines. In contrast, another EGFR inhibitor, erlotinib, had no effect against ZAP-70+ CLL cells indicating that gefitinib was inhibiting a kinase unaffected by erlotinib. When Jurakat and ZAP-70+ CLL cells were treated with gefitinib, there was reduced total tyrosine phosphorylation and decreased tyrosine phosphorylation of ZAP-70, and Syk but no difference in Lyn phosphorylation. Furthermore, gefitinib blocked B cell receptor activation and mediated cell survival. Taken together, these results indicate that gefitinib may be useful agent in the treatment of ZAP-70+ CLL, either alone or in combination with fludarabine or chlorambucil. Ongoing studies are determining the precise mechanism of action of gefitinib in ZAP-70+ CLL and assessing its effects on the CLL microenvironment. 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 5232. doi:1538-7445.AM2012-5232
Treatment and survival among 1594 patients with ATL
Authors: Hiroo Katsuya, Kenji Ishitsuka, Atae Utsunomiya, Shuichi Hanada, Tetsuya Eto, Yukiyoshi Moriuchi, Yoshio Saburi, Masaharu Miyahara, Eisaburo Sueoka, Naokuni Uike, Shinichiro Yoshida, Kiyoshi Yamashita, Kunihiro Tsukasaki, Hitoshi Suzushima, Yuju Ohno, Hitoshi Matsuoka, Tatsuro Jo, Masahiro Amano, Ryosuke Hino, Mototsugu Shimokawa, Kazuhiro Kawai, Junji Suzumiya, Kazuo Tamura
Journal: Blood (2015)