tbuckley/cabot-search huggingface dataset:
Inhomogeneous crystal grain formation in DPPC-DSPC based thermosensitive liposomes determines content release kinetics
Authors: Tao Lu, Timo L.M. ten Hagen
Journal: Journal of Controlled Release (2016)

Thermosensitive liposomes (TSL) receive attention due to their rapid externally controlled drug release at transition temperature in combination with hyperthermia. This rapid release feature of TSL occurs when the liposome membrane is going through a phase change which results in numerous interfaces, at so-called crystal grain boundaries. Based on experience with TSLs, our group found that thermosensitive liposomes formulated by binary compositions of DPPC and DSPC at proper ratios are able to exhibit rapid release without incorporation of release-promoting components. The aim of this study was to understand the mechanism of rapid release from bi-component DPPC-DSPC based TSL. Based on the investigation of a series of TSLs formulated by different DPPC-DSPC ratios, and through the analysis of binary-phase diagrams of DPPC-DSPC TSLs, we conclude that inhomogeneous crystal grains are formed in bi-component TSL membranes rather than mono-component, thereby facilitating content release. The resulting inhomogeneous membrane pattern is affected by DPPC/DSPC ratio, i.e. this determines the number of interfaces between solid and liquid phases at transition temperature, which can be diminished by addition of cholesterol. At appropriate DPPC/DSPC ratio, substantive solid/liquid interfaces can be generated not only between membrane domains but also between crystal grains in each domain of the liposome membranes, therefore improving content release from the TSL at transition temperatures.
Effective Translation of Research to Practice: Hospital-Based Rehabilitation Program Improves Health-Related Physical Fitness and Quality of Life of Cancer Survivors
Authors: Amy A. Kirkham, Riggs J. Klika, Tara Ballard, Paul Downey, Kristin L. Campbell
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Although exercise has been widely established as an efficacious rehabilitative therapy for cancer survivors in rigorously designed research studies, demonstration of translation of this research into clinical oncology practice is needed. The purpose of this study was to evaluate the effectiveness of a real-world cancer rehabilitation program implemented within a healthcare setting. Patients and Methods: This study involved 299 adult cancer survivors enrolled in a hospital-based, supervised, individualized, cancer rehabilitation program. A retrospective review of the 132 participants who completed the follow-up assessment was performed. Sixty-minute sessions consisting of aerobic, resistance, flexibility, and relaxation exercises were performed twice weekly. Questionnaires and fitness assessments were administered at enrollment and after 24 sessions by exercise physiologists. Change in a number of health-related physical fitness and patient-reported outcomes and the influence of baseline characteristics on program outcomes were assessed. Results: There were no baseline differences between those who completed the follow-up assessment and those who withdrew. Statistically and/or clinically meaningful improvements occurred in functional capacity, blood pressure, muscular endurance, flexibility, health-related quality of life, and fatigue, but not in body composition. Age, marital status, radiation treatment status, exercise frequency before diagnosis, smoking status, and alcohol consumption frequency influenced functional capacity and/or quality-of-life changes. Conclusions: Adoption of cancer rehabilitation as a standard part of oncology care may improve cancer survivors' health and well-being.
Prospective Randomized Comparison of High Dose AraC and AutoPBSCT as Late Consolidation for Patients ≤60 Years with Standard Risk AML: Final Results of the AML SHG-Hannover 01/99 Trial.
Authors: Arnold Ganser, Jürgen Krauter, Dieter Hoelzer, Oliver G. Ottmann, Hans Martin, Michael Lubbert, Jurgen Finke, Wolfgang F.W. Heit, Walter Fiedler, Lothar Kanz, Gunter Schlimok, Hartmut H. Kirchner, Aruna Raghavachar, Wolfram Brugger, Gerhard Heil
Journal: Blood (2006)
Abdominal CT in the Clinical Evaluation of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract: Diffuse Small Intestine Involvement Is Associated with Severity and Outcome.
Authors: Avichai Shimoni, Marjory Hertz, Moshe Yeshurun, Orit Portnoy, Izhar Hardan, Michal Amitai, Arnon Nagler, Sara Apter
Journal: Blood (2004)
Abstract 5061: Astrocytes promote medulloblastoma tumorigenesis via sonic hedgehog secretion
Authors: Larra Walling Yuelling, Fang Du, Eric Lee, Renata Muradimova, Peng Li, Zeng-jie Yang
Journal: Cancer Research (2015)

Abstract Tumor development is a complex process that involves interactions between tumor cells and the surrounding cells (the microenvironment). However, in medulloblastoma (MB), the most common malignant pediatric brain tumor, the contribution of the tumor microenvironment in tumorigenesis still remains elusive. Using MB mouse models, we have recently found that astrocytes represent the major component of the MB microenvironment. Astrocytes significantly enhance MB cell proliferation in vitro and genetic ablation of astrocytes dramatically prevents MB cell proliferation and inhibits MB growth in tumor-bearing mice. These results indicate the critical role of astrocytes during MB development. Our studies have further revealed that astrocytes stimulate proliferation of MB cells by secretion of sonic hedgehog (Shh), a mitogen required for neuronal proliferation during normal development. It is well established that Shh triggers canonical hedgehog signaling via activation of the Gli1 transcription factor. Interestingly, astrocyte-derived Shh stimulates MB cell proliferation independent of Gli1 activation, suggesting that astrocytes promote MB tumorigenesis through a novel Shh signaling pathway. Together, our studies shed light on the important function of the tumor microenvironment in MB initiation and progression, and pave the road to develop therapeutic approaches to treat MB by targeting Shh secretion in astrocytes. Note: This abstract was not presented at the meeting. Citation Format: Larra Walling Yuelling, Fang Du, Eric Lee, Renata Muradimova, Peng Li, Zeng-jie Yang. Astrocytes promote medulloblastoma tumorigenesis via sonic hedgehog secretion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5061. doi:10.1158/1538-7445.AM2015-5061
Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma.
Authors: M. E. Valsecchi, D. Summers, C. M. Intenzo, S. Kim, M. J. Mastrangelo, T. Sato
Journal: Journal of Clinical Oncology (2011)

8552 Background: Uveal melanoma is the most common primary intraocular cancer in adults. However, it is still a rare disease where large clinical trials are difficult to achieve. Approximately 50% of the patients will develop distant metastases, urging for a continuous search of new strategies to improve the quality of life and prolong survival. Since uveal melanoma originates in the neural crest, it may share the same characteristics as neuro-endocrine tumors, raising the question whether somatostatin-receptors expression is present and play any role in these patients. Methods: We studied heavily pre-treated patients with metastatic uveal melanoma with somatostatin receptor scintigraphy (SRS). Using standard protocol technique, planar images of the whole body complemented by SPECT on suspected sites were acquired between 4, 24 and 48 hours after intravenous administration of 5-6 mCi of 111Indium-octeotride. Clinical and pathological information was also recollected. Univariate analyses were undertaken to explore the relationship between selected variables and the SRS results. In 7 patients, sandostatin LAR Depot 20 mg IM monthly was used in a compassionate fashion with therapeutic intention. Results: A total of 30 Caucasian patients were included. The median age was 48.5 years old (min 24; max 68) and 13 (43%) were males. All had extensive metastatic disease and the median lines of treatment received were 3. SRS was found to be positive in 14 (46%) of the patients. SRS results were not related to gender, type of treatment, tumor site or histological type. Data on monosomy 3 was available for 5 patients, 4 of whom (80%) were SRS positive. SRS positive patients tend to have more extra-hepatic involvement (P =.04). Two of the 7 patients who received sandostatin died within a month of receiving the first dose due to very advanced disease, but another two (28.5%) had stable disease for ≥ 5 months. The median time to progression on sandostatin was 2.1 months. Conclusions: We found that almost half of the patients with metastatic uveal melanoma express somatostatin receptors. This fact may be used to explore innovative therapeutic approaches such as somatostatin analogues, radioactive particles or toxin conjugated agents targeting that receptor.
Abstract 343: Inactivation of the P2Y2 Receptor Gene Reduces Atherosclerosis
Authors: Cheikh Seye, Yucksel Agca, Shaomin Qian
Journal: Circulation Research (2012)

Rationale: Nucleotides acting via P2Y 2 nucleotide receptors (P2Y 2 R) regulate both migration of vascular smooth muscle cells and endothelial recruitment of monocyte/macrophage in vivo. Objective: We aimed to determine whether inactivation of the P2Y 2 R gene protects against neointima hyperplasia and atherosclerosis. Method and results: We performed femoral artery cuff injury in wild-type and P2Y 2 R -/- mice and examined neointima formation 14 days after injury, the time corresponding to peak SMC accumulation in this model. Wild-type mice exhibited a 190% increase in cellular proliferation ( P &lt;0.001) in the arterial wall as assessed by BrdU incorporation, and a 150% increase in neointima formation ( P =0.010) compared to wild-type mice. There was no significant difference in the medial area between wild type and P2Y 2 R -/- mice. To assess the contribution of P2Y 2 R to atherosclerosis, we first generated P2Y 2 R -/- /ApoE -/- mice by mating ApoE -/- mice with P2Y 2 R -/- mice. We then examined the development of atherosclerotic lesions 30 weeks after mice were fed with standard chow diet, the time corresponding to widespread atherosclerotic lesions in the ApoE -/- mouse model. P2Y 2 R -/- /ApoE -/- and ApoE -/- exhibited no differences in blood pressure, number of circulating leukocytes, differential counts, or total blood cholesterol. The surface covered by atherosclerotic lesions in the entire aorta was significantly reduced in P2Y 2 R -/- /ApoE -/- mice as compared to ApoE -/- . The total intimal lesion area in the aortic sinus was significantly less in P2Y 2 R -/- /ApoE -/- mice than in ApoE -/- mice. Mac-3 staining revealed a significant reduction in the percentage of total plaque area occupied by macrophages in P2Y 2 R -/- /ApoE -/- mice compared with Apo E -/- mice. Conclusion: These findings suggest that unraveling the molecular mechanisms associated with P2Y 2 R may lead to potential drug targets for the treatment of coronary syndromes and percutaneous coronary interventions.
Up-Regulation of NO/cGMP Signaling Pathway in Corpus Cavernosum of Sickle Cell Disease Transgenic Mice
Authors: Mário Angelo Claudino, Carla Fernanda Franco-Penteado, Marcus A.F. Corat, Luiz Augusto C Passos, Ana Paula Gimenes, Edson Antunes, Fernando F. Costa
Journal: Blood (2008)
Cytotoxicity of Genetically Engineered Fusion Protein with CD154 Peptide Mimetic (OmpC-CD154p) on B-NHL Cell Lines.
Authors: Bernardo Martinez-Miguel, Melisa A. Martinez-Paniagua, Sara Huerta-Yepez, Rogelio Hernandez-Pando, Cesar R. Gonzalez-Bonilla, Benjamin Bonavida, Mario I. Vega
Journal: Blood (2007)
Prognostic factors for colorectal cancer patients with pulmonary metastases
Authors: W. Li, W. Zhang, S. Cai, J. Yin, J. Li
Journal: Journal of Clinical Oncology (2009)

e15107 Background: Pulmonary is the second common metastastic site of CRC with a good survival after metastasectomy, however the general situation of pulmonary metastases from CRC has received little attention, especially for unresectable ones. The aim of this study was to determine factors that may influence survival and disease free interval from primary radical surgery to pulmonary metastases (DFI). Methods: From 01/2000 to 11/2008, a total of 206 pts with pulmonary metastases (colon72, rectal ca131, 3 unknown) were collected retrospectively and the clinical data were analyzed using Kaplan-Meier survival curves, univariate and multivariate analysis. Results: 128 pts (62.1%) had lung disease as the first metastatic site and 33 pts (26.7%) had synchronous liver involvement. Only 17 patients (8.3%) followed pulmonary metastatic resection, and others underwent palliative medical treatment including the chemotherapy and intervention. Median survival was 16.0 months (range 12.240–19.760) with a 18% 5-year survival. Of the totally 160 patients who had synchronous pulmonary metastases after radical primary tumor surgery, the mDFI was 20 months (range 16.738–23.262) months. Rectal cancer had a high chance (65%) for lung recurrence with longer DFI (21 vs 14 mo, P=0.02), but no difference of survival was shown compared to colon cancer. Factors that significantly predicted a poor prognosis on univariate analysis included vessel invasion (P=0.022) and high T stage (P=0.009), but neither of them was the independent prognostic factors after multivariate analysis. The factors influencing the DFI of metachronous pulmonary metastases included primary tumor site, pathological morphology, tumor infiltration stage and regional lymph node stage (P&lt;0.05). There was a trend of better survival of patients receiving resection surgery after pulmonary metastases than receiving chemotherapy alone though no statistical significant was reached (mOS:34 vs 16 mo, P=0.125). But to patients who receiving metastatic site resection, chemotherapy after surgery improved the survival (P=0.042). Conclusions: No independent prognostic factors of survival had been found. The invasive tumor with high stage may have a shorter disease free interval of pulmonary metastases after primary surgery. No significant financial relationships to disclose.
Detection of Minimal Residual Disease by Flow-Cytometry Otimizes Risk Stratification When Combined with Cytogenetics in AML.
Authors: Francesco Buccisano, Luca Maurillo, Giovanni Del Poeta, Maria Ilaria Del Principe, Paola Panetta, Daniela Fraboni, Maria Irno Consalvo, Daniela Renzi, Selenia Campagna, Chiara Sarlo, Luca Franceschini, Laura Giannì, Emanuele Ammatuna, Francesco Lo Coco, Sergio Amadori, Adriano Venditti
Journal: Blood (2007)
Analysis of the Incidence and Characteristics of Venoocclusive Disease (VOD) of the Liver in Pediatric Hematopoietic Progenitor Cell Transplant (HPCT) Patients with Heparin Alone Vs. Heparin and Ursodiol Prophylaxis at the Medical College of Wisconsin.
Authors: Julie-An Talano, Jessica Brown, Jennifer McArthur, Mollie Mulberry, Daniel Eastwood, Kwang Woo Ahn, James T. Casper, David Margolis
Journal: Blood (2009)
402. Mesenchymal Stromal Cells Can Ameliorate the Progressive Phenotype of Dog With Duchenne Muscular Dystrophy
Authors: Yuko N. Kasahara, Hiromi H. Kinoh, Mutsuki Kuraoka, Tomoko Chiyo, Hironori Okada, Nana Tsumita, Kiwamu Imagawa, Katsuhiko Tachibana, Shin'ichi Takeda, Takashi Okada
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) is an incurable genetic disease with early mortality that exhibits skeletal muscle weakness with chronic inflammation. Multipotent mesenchymal stromal cells (MSCs) could be a potential therapeutics because of their immunosuppressive properties and ability of differentiation to myogenic cells in situ. In the present study, we examined the strategies for effective cell transplantation to develop a novel approach for functional recovery of the skeletal muscles using a dog model of Duchenne muscular dystrophy. Human bone marrow-derived MSCs were intravenously injected into two littermates of canine X-linked muscular dystrophy in Japan (CXMDJ) at weekly interval for 8 weeks without immunosuppression. Clinical phenotypes on transplanted dogs were analyzed by using blood exams, physical capacity, MRI and histology compared with two non-injected littermates as controls. The downregulation of inflammation in the lower legs of MSCs-treated CXMDJ was confirmed by magnetic resonance imaging analysis. Immunofluorescence analysis showed decreased area of IgG-positive necrotic myofibers and also increased number of developmental myosin heavy chain-positive regenerative fibers. Impaired tetanic force of gastrocnemius of CXMDJ recovered in hMSCs-treated CXMDJ, from 25% to 80% of wild type. Although CXMDJ showed progressive muscle atrophy in the all four limbs, exercise intolerance and abnormal locomortion, we observed improved phenotypes in the hMSCs-treated CXMDJ along with the improved pace of flip-flop and running. We demonstrated that the systemic injection of MSCs ameliorates the progressive phenotype in CXMDJ. The therapeutic effects might be associated with the production of paracrine or endocrine factors that regulate inflammation, and might also stimulate the proliferation of endogenous stem cells at the injured muscle tissue. This strategy of MSCs treatment would be promising for the future DMD cell therapy.
An Autophagy Inhibitor, Chloroquine, Overcomes An Imatinib-Resistant T315I Mutant of Bcr/Abl, Whose Latent May Exist Before Imatinib Treatment.
Authors: Yuko Mishima, Yuji Mishima, Yasuhito Terui, Shinya Kimura, Kiyohiko Hatake
Journal: Blood (2009)
Platelet/Megakaryocyte PKC-Θ Is a Transcriptional Target of RUNX1/ CBFA2: Studies in Human RUNX1 Haplodeficiency.
Authors: Gauthami S Jalagadugula, Gurpreet Kaur, Guangfen Mao, Danny Dhanasekaran, A. Koneti Rao
Journal: Blood (2008)
Abstract 1512: Cancer stemness property incurred by inflammatory cytokine confers poor prognosis of hepatocellular carcinoma
Authors: Te-Sheng Chang, Yu-Chih Wu, Ying-Huang Tsai, Yen-Hua Huang
Journal: Cancer Research (2015)

Abstract Purpose: To unravel the role of inflammatory cytokine IL-6 and IGF-1 receptor (IGF-1R) in expressing stemness-related properties and to evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG, and IGF-1R in hepatocellular carcinoma (HCC). Experimental Design: Frozen liver and HCC tissue samples were obtained from 191 patients who received curative hepatectomy between 2004 and 2012. Serum levels of IL-6 were detected using ELISA assays (n = 120). The effects of IL-6/IGF-1 on stemness expression in HCC were examined using OCT4/NANOG promoter luciferase reporter, RNA interference, secondary sphere formation, side population, and xenograft animal models. The OCT4/NANOG protein and phospho-IGF-1 receptor (p-IGF-1R) in tissues were detected by western blotting (n = 8) and immunohistochemical staining (n = 85). OCT4, NANOG, and IGF-1R expression levels in tissues (n = 191) were analyzed by real-time Q-PCR and was correlated with early tumor recurrence using Kaplan-Meier survival analysis. Results: A high positive correlation between the expression levels of OCT4/NANOG and IGF-1R/p-IGF-1R in human HCC tissues was observed. The concurrent expression of OCT4/NANOG/IGF-1R was mostly confined to HBV-related HCC (HBV-HCC) and was significantly correlated with early tumor recurrence. High serum levels of IL-6 were significantly correlated with high OCT4/NANOG expression. IL-6 stimulated an autocrine IGF-1/IGF-1R expression STAT3-dependently, which stimulated stemness-related properties in both the cell lines and the xenografted mouse tumors. The inhibition of IGF-1R activation by either RNA interference or by treatment with the inhibitor picropodophyllin (PPP) significantly suppressed the IL-6-induced stemness-related properties both in vitro and in vivo. Conclusions: The expression of pluripotency-related genes is associated with early tumor recurrence and is regulated by IL-6-induced IGF/IGF-1R activation, particularly in HBV-HCC. Citation Format: Te-Sheng Chang, Yu-Chih Wu, Ying-Huang Tsai, Yen-Hua Huang. Cancer stemness property incurred by inflammatory cytokine confers poor prognosis of hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1512. doi:10.1158/1538-7445.AM2015-1512
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Authors: Roman A Romanov, Amit Zeisel, Joanne Bakker, Fatima Girach, Arash Hellysaz, Raju Tomer, Alán Alpár, Jan Mulder, Frédéric Clotman, Erik Keimpema, Brian Hsueh, Ailey K Crow, Henrik Martens, Christian Schwindling, Daniela Calvigioni, Jaideep S Bains, Zoltán Máté, Gábor Szabó, Yuchio Yanagawa, Ming-Dong Zhang, Andre Rendeiro, Matthias Farlik, Mathias Uhlén, Peer Wulff, Christoph Bock, Christian Broberger, Karl Deisseroth, Tomas Hökfelt, Sten Linnarsson, Tamas L Horvath, Tibor Harkany
Journal: Nature Neuroscience (2016)
Angiogenesis polymorphisms profile in the prediction of clinical outcome of advanced HCC patients receiving sorafenib: combined analysis of VEGF and HIF-1a. Final results of the ALICE-2 study
Authors: L. Faloppi, A. Casadei Gardini, G. Masi, N. Silvestris, C. Loretelli, P. Ulivi, C. Vivaldi, M. Bianconi, R. Giampieri, A. Bittoni, K. Andrikou, M. Del Prete, C.D. Gadaleta, M. Scartozzi, S. Cascinu
Journal: Annals of Oncology (2015)
Abstract 1029: Receptor-interacting protein kinase 1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy
Authors: Xu Guang Yan, Qi Luan, Lei Jin, Chen Chen Jiang, Kwang Hong Tay, Fritz Lai, Xiao Ying Liu, Yi Lun Liu, Su Tang Guo, Hsin-Yi Tseng, Xu Dong Zhang
Journal: Cancer Research (2015)

Abstract Although receptor-interacting protein kinase 1 (RIP1) is emerging as a critical determinant of cell fate in response to cellular stress resulting from activation of death receptors and DNA damage, its potential role in response of cells to endoplasmic reticulum (ER) stress remains undefined. Here we report that RIP1 functions as an important pro-survival mechanism in melanoma cells undergoing ER stress through activation of autophagy. While pharmacological induction of ER stress upregulated RIP1 and triggered autophagy in melanoma cells resistant to ER stress-induced apoptosis, knockdown of RIP1 inhibited autophagy and rendered the cells sensitive to killing by ER stress, recapitulating the effect of inhibition of autophagy. Consistently, overexpression of RIP1 enhanced induction of autophagy and conferred resistance of melanoma cells to killing by ER stress. Activation of JNK, which phosphorylated the BH3-only protein Bim leading to its dissociation from Beclin-1, was involved in ER stress-induced, RIP1-mediated activation of autophagy in melanoma cells. On the other hand, activation of the transcription factor heat shock factor protein 1 (HSF1) downstream of the IRE1/XBP1 axis of the unfolded protein response was responsible for the increase in RIP1 in melanoma cells undergoing ER stress. Collectively, these results identify upregulation of RIP1 as an important adaptive mechanism of melanoma cells to ER stress by protecting against cell death through activation of autophagy, and suggest that targeting the autophagy-activating mechanism of RIP1 may be a useful strategy to enhance sensitivity of melanoma cells to therapeutic agents that induce ER stress. Citation Format: Xu Guang Yan, Qi Luan, Lei Jin, Chen Chen Jiang, Kwang Hong Tay, Fritz Lai, Xiao Ying Liu, Yi Lun Liu, Su Tang Guo, Hsin-Yi Tseng, Xu Dong Zhang. Receptor-interacting protein kinase 1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1029. doi:10.1158/1538-7445.AM2015-1029