tbuckley/cabot-search huggingface dataset:
Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion
Authors: Shuxin Shen, Ying Li, Yunbin Xiao, Zonglei Zhao, Chuanxi Zhang, Junfen Wang, Hairui Li, Feng Liu, Nvqin He, Ye Yuan, Yongkang Lu, Shengcun Guo, Yan Wang, Wangjun Liao, Yulin Liao, Yanmei Chen, Jianping Bin
Journal: Biomaterials (2018)

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.
Abstract 4489: Effect of cancer-associated fibroblasts on the progression of malignant melanoma cells
Authors: Heishiro Fujikawa, Masakazu Yashiro, Takaharu Hatano, Shusaku Maeda, Hisashi Motomura
Journal: Cancer Research (2018)

Abstract Introduction Malignant solid tumor is composed of not only cancer cells but also various types of stromal cells, which include fibroblasts, vascular endothelial cells, and immune cells. Currently, it has been reported that fibroblasts in tumor stroma, namely cancer-associated fibroblasts (CAFs), might affect cancer progression. Some studies suggested that CAFs have the stimulation-activity of the malignant potential of melanoma cells, but some reports mentioned their inhibitory-activity of melanoma cells. In this study, we investigated the effects of CAFs on the proliferation and invasion ability of malignant melanoma cells. Material and Method We used 2 malignant melanoma cell lines, MMAc and COLO679. Three CAFs were established from sebaceous carcinoma or skin malignant melanoma. Serum-free conditioned medium (CAF-CM) from CAF was prepared as follows. CAF were seeded into 100 mm plastic dishes with 10 ml of DMEM containing 2% FCS. To obtain CAF-CM, CAF were washed by PBS and then incubated for 3 days with serum-free DMEM. The conditioned medium was collected as CAF-CM. Serum-free DMEM was used as the control. CAFs were used before the 15th passage in culture. The effect of CAF-CM on the proliferation of the melanoma cells was determined by cytometry assay using Coulter Counter. The effect of CAF-CM on the motility of the melanoma cells was examined by Matrigel-invasion assay. Result CAF-CM significantly increased the proliferation of melanoma cell, in compared the control. Under the condition of adding 25% of CAF-CM, the number of MMAc cells were increased about 300% after 72 hours of incubation, and 105% after 120 hours of incubation that of COLO679 increased about 56% after 72 hours of incubation, 130% after 120 hours of incubation. CAF-CM significantly increased the invasion of MMAc cells. The invasion of MMAc cells were increased about 200% after 72 hours of incubation following the addiction of 25% CAF-CM. In contrast, CAF-CM did not affect on the invasion of COLO679 cells. Conclusion CAFs are associated with the proliferation and invasion of malignant melanoma cells. Citation Format: Heishiro Fujikawa, Masakazu Yashiro, Takaharu Hatano, Shusaku Maeda, Hisashi Motomura. Effect of cancer-associated fibroblasts on the progression of malignant melanoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4489.
Reversal of Angiogenic Growth Factor Upregulation by Revascularization of Lower Limb Ischemia
Authors: PaoloPorcu, CostanzaEmanueli, MariaKapatsoris, JulieChao, LeeChao, PaoloMadeddu
Journal: Circulation (2002)

Background— Tissue kallikrein (tK) and vascular endothelial growth factor (VEGF) are potent angiogenic agents. Upregulation of tK or VEGF was documented in animal models of acute ischemia, yet it remains unknown whether these endothelial cell mitogens are overexpressed in chronic peripheral vascular insufficiency. Methods and Results— Circulating tK and VEGF were measured in 36 patients with symptomatic peripheral vascular disease before and after surgical revascularization. In 6 patients without symptoms at rest, tK was assayed after exercise stress test. VEGF levels fell within the normal range in all patients (96±11 versus 109±13 pg/mL in healthy control subjects, P=NS) and remained unchanged after revascularization. In contrast, tK expression was upregulated in 34 of 36 patients (1107±203 versus 85±10 pg/mL in control subjects, P<0.05), with no further increase after exercise. Tissue kallikrein levels in the venous effluent of ischemic limbs were found to be positively correlated with the number of an...
Disruption of Autosomal Recessive Hypercholesterolemia Gene Shows Different Phenotype In Vitro and In Vivo
Authors: MarikoHarada-Shiba, AtsukoTakagi, KousukeMarutsuka, SayakaMoriguchi, HiroakiYagyu, ShunIshibashi, YujiroAsada, ShinjiYokoyama
Journal: Circulation Research (2004)

We previously characterized the patients with autosomal recessive hypercholesterolemia (ARH) as having severe hypercholesterolemia and retarded plasma low-density lipoprotein (LDL) clearance despite normal LDL receptor (LDLR) function in their cultured fibroblasts, and we identified a mutation in the ARH locus in these patients. ARH protein is an adaptor protein of the LDL and reportedly modulates its internalization. We developed ARH knockout mice (ARH−/−) to study the function of this protein. Plasma total cholesterol level was higher in ARH−/− mice than that in wild-type mice (ARH+/+), being attributed to a 6-fold increase of LDL, whereas plasma lipoprotein was normal in the heterozygotes (ARH+/−). Clearance of 125I-LDL from plasma was retarded in ARH−/− mice, as much as that found in LDLR−/− mice. Fluorescence activity of the intravenously injected 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-LDL was recovered in the cytosol of the hepatocytes of ARH+/+ mice, but not in tho...
Brown Adipose Tissue Controls Skeletal Muscle Function via the Secretion of Myostatin
Authors: Xingxing Kong, Ting Yao, Peng Zhou, Lawrence Kazak, Danielle Tenen, Anna Lyubetskaya, Brian A. Dawes, Linus Tsai, Barbara B. Kahn, Bruce M. Spiegelman, Tiemin Liu, Evan D. Rosen
Journal: Cell Metabolism (2018)
AB1454-HPR Interactions between women with rheumatoid arthritis and nurses in nursing consultations – balancing illness, motherhood and work life
Authors: H Feddersen, T.M. Kristiansen, P.T. Andersen, K. Hørslev-Petersen, J. Primdahl
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are offered outpatient follow-up in nurse-led consultations.<sup>1</sup> RA affects almost every aspect of daily life,.<sup>2</sup> Many women with rheumatoid arthritis find it challenging to be mothers and simultaneously participate in paid work.<sup>3</sup> <h3>Objectives</h3> To investigate how women's understanding of RA, motherhood and working life are parts of the interactions with nurses during nursing consultations. <h3>Methods</h3> Participant observations were conducted during 10 women's attendance in nursing consultations and subsequently the women were interviewed about their experiences. Data generation and analysis were carried out according to the principles of constructivist grounded theory.<sup>4</sup> <h3>Results</h3> A core category was developed: <i>"Cooperation through mutual recognition"</i> which describes how women and nurses through verbal and non-verbal communication confirm their common understanding of the content and form of nursing consulting. Furthermore, three sub-categories were identified: <i>1) "On safe ground"</i> illuminates, that biomedical aspects of the disease such as blood tests results, examination of the joints and pharmacological treatments represent the foundation of the dialogue. This interaction has elements that may be characterised as ritualised behaviour. 2)<i> "Taking risks"</i> documents how both parties are more aware of the counterparts' reaction when it comes to dialogue concerning how the women manage illness in everyday life along with motherhood and paid work. 3) <i>"Gentle correction"</i> shows how the nurses gently express when they find the women's talk is too far out. <h3>Conclusions</h3> The biomedical aspects of the disease (disease perspective) constitute the starting point for a discussion and allow both parts to initiate conversations on the women's subjective understanding (illness perspective) of how illness, motherhood, and work are managed. <h3>References</h3> [1] de Thurah, A., et al., <i>Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis: a systematic review and meta-analysis.</i> RMD Open, 2017. 3(2): p. e000481. [2] Kristiansen, T.M., et al., <i>It means everything: continuing normality of everyday life for people with rheumatoid arthritis in early remission</i>. Musculoskeletal Care, 2012. 10(3): p. 162–70. [3] Feddersen, H., et al., <i>Construction of meaningful identities in the context of rheumatoid arthritis, motherhood and paid work: A meta-ethnography</i>. Journal of Clinical Nursing, 2017. 26(23–24): p. 4117–4128. [4] Charmaz, K., Constructing Grounded Theory. 2nd ed. 2014, Los Angeles: Sage. <h3>Disclosure of Interest</h3> None declared
Abstract B74: Identification of prognostic molecular subtypes of ovarian serous cystadenocarcinoma by isoform-level gene expression analysis
Authors: Arunima Shilpi, Brandon L. Seagle, Manoj Kandpal, Shohreh Shahabi, Ramana V. Davuluri
Journal: Clinical Cancer Research (2018)

Abstract Characterization of molecular aberrations in ovarian serous cystadenocarcinoma (OVSC) is highly crucial for developing precision medicine approaches. While gene-level analysis of gene expression profiles of The Cancer Genome Atlas (TCGA) OVSC samples revealed four molecular subgroups (differentiated, proliferative, mesenchymal, and immunoreactive), the association of the derived subtypes with the clinical and pathologic features, such as stage, cytoreduction, and chemotherapy, is not statistically significant. Considering the fact that the majority of human genes produce multiple transcript-variants that could be involved in different functional pathways, we reanalyzed the TCGA exon-array expression profiles at the transcript variant or isoform level by following the novel informatics methodology we developed and successfully applied for glioblastoma (Pal et al., Nucleic Acids Res 2014). Non-negative matrix factorization (NMF) clustering of TCGA ovarian serous adenocarcinoma samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 26% of the samples, resulting in significant (p=0.009) survival differences among the refined subgroups. The survival analysis was further extended to multivariate Cox proportional hazard model considering the different subgroups, and the clinical parameters as the predictor variables. Patients classified under mesenchymal group (HR = 1.44; 95% CI, 0.99-2.08; P &amp;lt; 0.05) and in stage III (HR = 2.39, 95%of CI, 1.25-4.56, P &amp;lt; 0.05), IV (HR= 3.16; 95% of CI, 1.58-6.32, P &amp;lt; 0.05) were identified to be at high risk or decreased survival, while those receiving intraperitoneal (IP) chemotherapy (HR, 0.63; 95% of CI, 0.38-1.03, P &amp;lt; 0.1) were associated with longer survival. We are in the process of translating the isoform-level gene signature into clinically adaptable molecular subtyping assay and validating on an independent patient cohort, with potential implications for developing robust diagnostic assays for OVSC patient stratification. Citation Format: Arunima Shilpi, Brandon L. Seagle, Manoj Kandpal, Shohreh Shahabi, Ramana V. Davuluri. Identification of prognostic molecular subtypes of ovarian serous cystadenocarcinoma by isoform-level gene expression analysis. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B74.
Abstract 10863: Long-term Use of Low-dose Aspirin Develops Proteinuria in Patients With Diabetes: A Reanalysis of JPAD Study
Authors: Sadanori Okada, Takeshi Morimoto, Hisao Ogawa, Mio Sakuma, Hirofumi Soejima, Makiko Ohtorii, Masafumi Nakayama, Naofumi Doi, Yasuhiro Akai, Hideaki Jinnouchi, Masako Waki, Seigo Sugiyama, Shiro Uemura, Yoshihiko Saito
Journal: Circulation (2013)

Objectives: Low-dose aspirin therapy is widely used for preventing cardiovascular diseases (CVD) all over the world. Patients at high CVD risk take aspirin through life; however, there is little ev...
Abstract 1586: Evaluation of AXL expression on circulating tumor cells from EGFR mutated lung cancer patients who have relapsed after the EGFR TKI treatment
Authors: Young Hun Kim, Myoung Shin Kim, Jun Sup Lee, Hyun Kyung Lee, Jae Hyuk Lee, Young Woong Sohn, Koichi Tazaki, Kenji Nakamaru, Kenichi Wakita, Byung Hee Jeon, Seokhyung Kim, Se-Hoon Lee
Journal: Cancer Research (2018)

Abstract Background: The EGFR (epidermal growth factor receptor) TKI (tyrosine kinase inhibitor) has become the standard treatment in lung cancer patients with EGFR mutations. When these patients are treated with EGFR TKI, 80~90% of the patients show responses to the drug. However the tumor begins to progress again following the development of resistance about 1 year later on average. About a half of resistance mechanisms are caused by the additional mutation of the EGFR gene (T790M), and the other half of the resistance mechanisms are caused by various mechanisms, with one of them being the overexpression of the AXL protein. Confirming AXL overexpression in circulating tumor cells (CTCs) can be an alternative method for tissue biopsy, but almost no research has been conducted on this so far. Here, we evaluate the AXL expression in CTC in case resistance occurs after the EGFR inhibitor treatment. Materials and Methods: The blood samples (10 ml) were collected from 10 EGFR TKI treated and relapsed lung cancer patients (TKI group) and 10 non-treated patients (control group). The blood samples were processed through Cytogen protocol to enrich CTCs. The enriched cells were immunofluorescent stained for CTC markers (EpCAM or Vimentin), AXL and WBC marker (CD45). The immunofluorescent stained cells were analyzed for each markers using Image Analysis program. Result: CTCs were detected by CTC markers in all patients from TKI group (range 0-210) and control group (range 1-42). AXL positive CTCs were detected in 9 out of 10 cases from TKI group and in all cases from control group. Interestingly, the quantification of AXL staining intensity in CTCs showed that AXL overexpression (3 fold or greater than baseline) was in 50% of TKI group and 20 % of control group. Conclusion: We have tested a new approach to evaluate the AXL overexpression in tumor cells of EGFR TKI resistant patients, and showed the feasibility of the this method. Most of lung cancer patients who undergo biopsy require hospitalization and some degree of complication due to biopsy is inevitable. Here we suggested that the blood-based method as a good alternative to the tissue biopsy in patients with tolerance. Citation Format: Young Hun Kim, Myoung Shin Kim, Jun Sup Lee, Hyun Kyung Lee, Jae Hyuk Lee, Young Woong Sohn, Koichi Tazaki, Kenji Nakamaru, Kenichi Wakita, Byung Hee Jeon, Seokhyung Kim, Se-Hoon Lee. Evaluation of AXL expression on circulating tumor cells from EGFR mutated lung cancer patients who have relapsed after the EGFR TKI treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1586.
Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study
Authors: Andrew Mente, Martin O'Donnell, Sumathy Rangarajan, Matthew McQueen, Gilles Dagenais, Andreas Wielgosz, Scott Lear, Shelly Tse Lap Ah, Li Wei, Rafael Diaz, Alvaro Avezum, Patricio Lopez-Jaramillo, Fernando Lanas, Prem Mony, Andrzej Szuba, Romaina Iqbal, Rita Yusuf, Noushin Mohammadifard, Rasha Khatib, Khalid Yusoff, Noorhassim Ismail, Sadi Gulec, Annika Rosengren, Afzalhussein Yusufali, Lanthe Kruger, Lungiswa Primrose Tsolekile, Jephat Chifamba, Antonio Dans, Khalid F Alhabib, Karen Yeates, Koon Teo, Salim Yusuf
Journal: The Lancet (2018)
Abstract 2548: An image-based method to detect and quantify T cell mediated cytotoxicity of 2D and 3D target cell models
Authors: Brad Larson, Diane Kambach, Wini Luty, Glauco Souza
Journal: Cancer Research (2018)

Abstract T cell-mediated cytotoxicity plays an important role in a suite of new methods being developed with the goal of incorporating a patient's immune system to combat cancer. The purpose of this study was to develop a sensitive, image-based in vitro method to evaluate and optimize adoptive T cell immunotherapies. Experiments were performed using MDA-MB-231 and fibroblast target cells co-cultured in 2D and 3D models, along with T cell to target cell ratios of 20:1, 10:1 and 5:1. T cell activation procedures were also tested where T cells were activated in the presence of anti-CD3 and anti-CD28 antibodies plus an IL-2 superkine only, or in a directed fashion with antibodies, superkine, and varying concentrations of target breast cancer cells. Experimental data show that directing the activation of T cells to recognize surface antigens on specific target cancer cells enhances the killing ability of the cells when compared to results from nondirected cells. In addition, increased T cell to target cell ratios induce higher levels of target cell cytotoxicity. Finally, it was evident that assay performance using 2D cultured target cells could be reliably carried out through a 72-hour incubation period. However, it exhibited limited utility beyond this point due to increasing numbers of uninduced necrotic cells within wells, negating the effect of test conditions. This phenomenon was unseen from 3D cultured target cells, indicating their ability to maintain a higher level of viability when cultured in this manner. Necrotic induction can then be reliably attributed to cell treatments using multiday incubations. The combination confirms the ability of the image-based method to deliver dependable results to assess T cell-mediated cytotoxicity using 2D and 3D target cell models. Citation Format: Brad Larson, Diane Kambach, Wini Luty, Glauco Souza. An image-based method to detect and quantify T cell mediated cytotoxicity of 2D and 3D target cell models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2548.
The prognostic value of serum CA 19-9 in patients with metastatic colorectal cancer.
Authors: Camilla Stedstrup Mosgaard, Mathias Holsey Gramkow, Christian Dehlendorff, Dorte Nielsen, Per Pfeiffer, Camilla Qvortrup, Mette K. N. Yilmaz, Ole Larsen, Stig Egil Bojesen, Jakob Vasehus Schou, Mogens Karsboel Boisen, Julia S. Johansen, Benny Vittrup Jensen
Journal: Journal of Clinical Oncology (2017)

e15131 Background: CEA is regarded as the marker of choice for monitoring patients with colorectal cancer (CRC), but the value of using CA19-9 is insufficient. The prognostic value of serum CA19-9 in combination with CEA was evaluated in patients with metastatic CRC (mCRC) before first (1) and third line therapy (3LT). Methods: From April 2004 to May 2015, pretreatment serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 [range 33-87] and male/female ratio 243(59%)/172(41%). Serum CA19-9 was determined by routine chemiluminescent immunometric assay (normal range 0-37 KU/l). Progression-free survival (PFS) and overall (OS) crude, adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were estimated using Cox regression analysis. CA19-9 and CEA were included as log 2 -transformed continuous variables and adjustment included mutually between CA19-9 and CEA in addition to primary tumor location, sex and age. Results: In 3LT median pretreatment CEA levels were higher than in 1LT (59 µg/l [IQR 14-288] vs. 23[6-153] P &lt; 0.01) while CA19-9 values were similar (112 KU/l [23-626] vs. 98[19-390]). In patients treated with 3LT univariate analysis showed that high levels of CA19-9 and CEA were associated with short PFS (CA19-9: HR = 1.06, 95% CI 1.02-1.10, P &lt; 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT neither CA19-9 nor CEA were significantly associated with PFS. In a multivariate analysis, none of the biomarkers were significantly associated with PFS. In patients treated with 3LT univariate analysis showed that high levels of CA 19-9 and CEA were associated with short OS (CA19-9: HR = 1.11, 1.07-1.16, P &lt; 0.01; CEA: HR = 1.1, 1.06-1.16, P &lt; 0.01). In patients treated with 1LT high levels of CA-19-9 but not CEA was significantly associated with a shorter OS (HR = 1.07, 1.00-1.14, P = 0.04). In 3LT multivariate analyses showed that high levels of CA19-9 and CEA were the only factors associated with a shorter OS (CA19-9: HR = 1.08, 1.03-1.13, P &lt; 0.01; CEA: HR = 1.07, 1.01-1.14, P &lt; 0.01), while there was no significant association to OS in 1LT. Conclusions: Serum CA19-9 may be a valuable prognostic biomarker in combination with CEA in mCRC patients receiving third line therapy.