tbuckley/cabot-search huggingface dataset:
Abstract 4030: Interactions between co-cultured myoblasts and prostate cancer cells kill myoblasts but promote cancer cell proliferation and fusion: implications for cachexia and metastasis to skeletal muscle
Authors: Berna Uygur, Evgenia Leikina, Leonid V. Chernomordik
Journal: Cancer Research (2015)

Abstract Severe muscle loss (cachexia) is the major cause for the cancer related death and 70% prostate cancer patients suffer from cachexia. Multinucleated cells of skeletal muscles are generated and regenerated by cell-to-cell fusion. It has been suggested that cell-to-cell fusion also takes place during carcinogenesis and promotes tumor cell diversity, drug resistance and the ability to metastasize. However fusion between cancer cells has remained elusive due to a very low efficiency of this process in earlier studies. Here we explored interactions between cancer cells and muscle environment in vitro. Co-culturing cells of human prostate cancer line (PC3) with primary murine proliferating myoblasts (muscle stem cells) resulted in differentiation and then apoptosis in muscle stem cells. Conditioned medium from PC3 cells also caused 50% decrease in proliferation of muscle stem cells. On the other hand, fusion-committed myoblasts co-cultured with PC3 cells lost their characteristic shapes and went through apoptosis. In addition to these effects of PC3 cells on murine myoblasts, we observed striking effects of myoblasts on PC3 cells. Co-culturing of PC3 cells with either proliferating myoblasts or fusion-committed myoblasts resulted in a robust fusion between cancer cells that yielded PC3 syncytia with up to 5 nuclei. Fusion promotion between PC3 cells was accompanied by a 1.5-fold increase in expression of Annexin A5, a protein recently implicated in myoblast fusion. In contrast, the expression of Annexin A5 in myoblasts was halved. Both co-culturing and using conditioned medium from fusion-committed myoblasts also resulted in a 2-fold increase in cancer cells proliferation and a 3-fold increase in the expression of the phosphorylated protein kinase AKT (pAKT). pAKT activity is associated with proliferation, drug resistance and cancer stem cell phenotype generation. Therefore we examined cancer stem cell marker, CD133 expression in PC3 cells. Treatment with conditioned medium from either proliferating or fusion-committed myoblasts doubled a percentage of CD133-expressing cells. Our results suggest an intriguing interplay between prostate cancer and muscle cells that may contribute to the progression of cancer and potentially explain cachexia. Citation Format: Berna Uygur, Evgenia Leikina, Leonid V. Chernomordik. Interactions between co-cultured myoblasts and prostate cancer cells kill myoblasts but promote cancer cell proliferation and fusion: implications for cachexia and metastasis to skeletal muscle. [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 4030. doi:10.1158/1538-7445.AM2015-4030
Minimal Residual Disease (MRD) and Risk-Oriented Therapy in Adult Acute Lymphoblastic Leukemia (ALL).
Authors: Renato Bassan, Orietta Spinelli, Elena Oldani, Tamara Intermesoli, Manuela Tosi, Giuseppe Rossi, Enrico M. Pogliani, Emanuele Angelucci, Pietro Fabris, Giorgio Lambertenghi-Deliliers, Paola Polistena, Eros Di Bona, Fabio Ciceri, Franco Leoni, Claudia Minotto, Daniele Mattei, Maurizio Musso, Tiziano Barbui, Alessandro Rambaldi
Journal: Blood (2005)
NHS approach to investigating patient deaths is poor, says regulator
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The NHS in England is failing patients by having inadequate, secretive, and defensive investigations into patient deaths, according to a review from the Care Quality Commission (CQC).

The commission said that current practice—which too often did not include families of the deceased patient being investigated—needed to change.

For its review, the commission looked at how NHS trusts across England identified, reported, investigated, and learnt from the deaths of people using their services, with a particular focus on people with mental health conditions and learning disabilities.

It gathered evidence during visits to a sample of 12 trusts; a national survey of all NHS trusts providing acute, mental health, and community services; and interviews with more than …
Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity
Authors: Christiane Wetzel, Simone Pifferi, Cristina Picci, Caglar Gök, Diana Hoffmann, Kiran K Bali, André Lampe, Liudmila Lapatsina, Raluca Fleischer, Ewan St John Smith, Valérie Bégay, Mirko Moroni, Luc Estebanez, Johannes Kühnemund, Jan Walcher, Edgar Specker, Martin Neuenschwander, Jens Peter von Kries, Volker Haucke, Rohini Kuner, James F A Poulet, Jan Schmoranzer, Kate Poole, Gary R Lewin
Journal: Nature Neuroscience (2016)
Acute Uric Acid Nephropathy
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Influence of Graft Versus-Host Disease Prophylaxis Regimen On T-Cell Repertoire Diversity Following Reduced-Intensity HLA-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Rachel B. Salit, Frances T. Hakim, Michael R. Bishop, Thea M. Friedman, Robert Korngold, Kira Goldgirsh, Sarfraz Memon, Seth M. Steinberg, David Liewehr, Daniel Peaceman, Jennifer Wilder, Kelly Bryant, Daniel H. Fowler, Juan Gea-Banacloche, Ronald E. Gress, Steven Z. Pavletic
Journal: Blood (2012)
Four Cases of Chronic Active Epstein-Barr Virus Infection That Performed Reduced-Intensity Conditioning Bone Marrow Transplantation.
Authors: Yuko Watanabe, Takeshi Rikiishi, Hidetaka Niizuma, Masaei Onuma, Yoshiyuki Hoshi, Yuka Saitou, Yohei Watanabe, Nobu Suzuki, Satoshi Horino, Yoji Sasahara, Osamu Sakamoto, Satoru Kumaki, Masayoshi Minegishi, Miki Sato, Ikuko Hakozaki, Looi ChungYeng, Akihiro Yachie, Shigeru Tsuchiya
Journal: Blood (2009)
Thymidylate-synthase poly-epitope peptide vaccination in pretreated metastatic cancer patients; a multi-arm phase Ib trial
Authors: P. Correale, C.B. Botta, E.C. Martino, C. Gandolfo, M.G. Rossetti, E. Dreassi, P. Tassone, P. Tagliaferri, L. Pirtoli, M.G. Cusi
Journal: Annals of Oncology (2015)
Abstract 949: An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells
Authors: Qingcong Lin, Junma Zhou, Jing Wang, Zonghui Wang, Jun Wang, Feng Chen, Xueming Qian, Xiao Shang, Jun Bao, Zhaoyi Wang, Kun Meng
Journal: Cancer Research (2015)

Abstract ER-α36 is a novel variant of ER-α, plays an important role in mitogenic estrogen signaling and tamoxifen resistance in both ER-positive and -negative breast cancer. ER-α36 is highly expressed on the plasma membrane of both ER-positive and -negative breast cancer stem/progenitor cells and critical for maintenance of the breast cancer stem/progenitor cells, which make it a promising target for antibody-based breast cancer treatment. In this study, we have screened and identified a candidate of therapeutic antibody named 3C11 that specifically recognizes ER-α36 at its unique C-terminal residues. The antibody 3C11 showed pM affinity to ER-α36 in the BiaCore assay and potent growth inhibitory activity in multiple breast cancer cell lines in vitro. In addition, 3C11 also showed dose-dependent inhibition of tumor growth in a xenograft model formed by a triple-negative breast cancer cell line SUM159 that was generated from a refractory breast cancer. Furthermore, we found that 3C11 was quickly and efficiently internalized into cells, which makes it a potential candidate for development of the antibody-drug conjugate approaches. These results demonstrated that ER-α36 is promising cancer target for development of antibody-based therapeutic approaches. Citation Format: Qingcong Lin, Junma Zhou, Jing Wang, Zonghui Wang, Jun Wang, Feng Chen, Xueming Qian, Xiao Shang, Jun Bao, Zhaoyi Wang, Kun Meng. An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells. [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 949. doi:10.1158/1538-7445.AM2015-949
In vitro effects of the novel JAK II inhibitor BSK805 in BCR-ABL and JAK II V617F-positive cell lines.
Authors: F. Ringel, J. Kaeda, M. Schwarz, B. Dörken, P. D. le Coutre
Journal: Journal of Clinical Oncology (2011)

e13563 Background: Janus kinases are critical components of cytokine signaling pathways that regulate hematopoiesis, growth, immunity, inflammation, and development. Oncogenic mutations of the nonreceptor tyrosine kinase JAK II can be found in a large part of Philadelphia chromosome negative myeloproliferative neoplasms. The V617F mutation occurs in 95% of patients with polycythemia vera, 55% with essential thrombocythemia and in 65% with primary myelofibrosis. Preclinical results strongly support that JAK II inhibitors could be effectively used in these indications. V617F causes a permanent activation of the JAK-STAT pathway leading to continous proliferation. Therefore, inhibitors of JAK II are under investigation to create new therapy strategies for MPNs. In this project the role of JAK II inhibitors in BCR-ABL positive cells should be investigated. Methods: The in vitro activity of BSK805, a new JAK II inhibitor (Novartis Pharmaceuticals), was analyzed in 10 hematopoietic cell lines, including 5 BCR-ABL positive (K-562, KCL-22, KU812, Lama-87, BV173), 4 JAK II V617F positive (CHRF-288, SET-2, UKE-1, HEL) and the T cell leukemia line Jurkat. Concentration kinetics from 0 up to 25 µM were established using XTT proliferation assay and flow cytometry for measuring apoptosis. Both new drugs were tested in addition together with imatinib and nilotinib. Results: 3 of the 4 tested V617F positive cell lines (CHRF-288, SET-2, UKE-1) showed a significant reduction of proliferation as well as viability compared to the other cell lines. CHRF-288 responded best to BSK805 at IC50 of 0.22 ± 0.04 µM. UKE-1 and SET-2 had similar values of 0.35 ± 0.03 µM and 0.37 ± 0.05 µM. Interestingly, HEL (V617F positive) showed only an IC50 value (1.8 ± 0.17 µM) for BSK805 comparable with the non mutated CML cell lines (1.5 to 2.5 µM). Each cell line responded to concentrations higher than 25 µM with reduced proliferation due to inhibition of various kinases. Combination of the JAK II inhibitors with Imatinib and Nilotinib showed no significant additive or synergistic effects. Conclusions: Here we tested a new JAK II inhibitor for cells carrying the V617F mutation. In cells not harbouring V617F no significant inhibition of proliferation was detected.
Molecular Analyses Of The Effects Induced By Orally Administered Bortezomib In Drosophila Flies: A Novel In Vivo Experimental Platform To Screen For The Tissue- and Age-Dependent Effects Of Proteasome Inhibitors
Authors: Eleni N. Tsakiri, Evangelos Terpos, Gerasimos P. Sykiotis, Issidora S. Papassideri, Vassilis G. Gorgoulis, Dirk Bohmann, Meletios A. Dimopoulos, Ioannis P. Trougakos
Journal: Blood (2013)
73. Effects of the Innate Immune System on Oncolytic Measles Virotherapy
Authors: Cheyne Kurokawa, Ianko Iankov, Ileana Aderca, Matthew Maurer, Keith Anderson, Sue Greiner, Marc Becker, Paul Haluska, Evanthia Galanis
Journal: Molecular Therapy (2015)

Vaccine strain derived Measles Virus is currently being tested in clinical trials for the treatment of several tumor types. Clinical response to MV therapy can vary, despite similar stages of disease, pre-existing antibody titers and MV entry receptor expression among treated patients. By using Next-Gen Sequencing in tumor samples deriving from ovarian cancer (OvCa) and glioblastoma (GBM) patients who were treated with MV in clinical trials, we observed that expression of interferon-stimulated genes (ISG), such as IFI44, MX1, MX2, RSAD2, and IFI27, correlated with permissiveness to MV infection and clinical outcome. Therefore, we hypothesized that elevated baseline levels of ISG expression directly confers resistance to MV infection in GBM and OvCa patients, and can possibly serve as predictive markers of response to MV therapy. To test this hypothesis we have assessed the baseline ISG expression in 27 primary patient-derived GBM xenograft lines. We found that 4 of the 27 lines have elevated baseline levels of ISG expression. Four primary GBM lines with low baseline levels of ISG expression were infected with MV-NIS (MOI 1 and 0.1). Upon infection, these cells were effectively killed and produced high titers of virus (>104 TCID50/ml by 48hr). In contrast, three primary GBM lines with high baseline levels of ISG expression were resistant to cell killing and produced significantly less virus upon infection with MV-NIS (MOI 1 and 0.1). ISG expression is regulated by the ISGF-3 complex via Stat-1/-2 and Jak-1 activation. Treatment with 3μm of the FDA approved Jak1/2 inhibitor ruxolitinib (Jakafi) for 48hr prior to MV infection (MOI 1 and 0.1) significantly increased MV production and cell killing in the high ISG expressing primary GBM39 line. The observed Jakafi effect is mediated via decreased ISG expression both at baseline and in response to MV infection. Experiments assessing the use of Jakafi in combination with MV in vivo are ongoing. In order to explore an association between ISG expression and MV restriction in OvCa patients, we assessed baseline ISG expression in 118 primary patient-derived ovarian xenograft lines. We found that 57 of the 118 samples have elevated baseline levels of ISG expression. MV therapy in an OvCa xenograft with low baseline levels of ISG expression led to significant prolongation of survival. Ongoing in vivo work in orthotopic ovarian models with variable ISG levels is assessing the association with efficacy of MV therapy. These experiments can lead to elucidation of the role baseline ISG expression plays in controlling response to MV therapy, which could be critical for patient selection and future clinical trial planning. Funding by: Brain SPORE (P50 CA108961), R01 CA154348 and Ovarian SPORE (P50 CA136393)
Herpes Simplex Virus Encephalitis (HSE) after Allogeneic Hematopoietic Stem Cell Transplatation (alloHSCT): Impact of Early Diagnosis and Treatment on Outcome.
Authors: Irene M. Cavattoni, Enrico Morello, Marco Casini, Norma Decaminada, Leonardo Pagani, Pietro Fabris, Sergio Cortelazzo
Journal: Blood (2007)
A Retrospective Survey of Imatinib Mesylate Treatment for Chronic Myeloid Leukemia in a Northern France Region.
Authors: Selim Corm, Ariane Leroyer, Mathieu Wemeau, Bruno Bregman, Abderrahim Oukessou, Michiel Hemels, Claude Preudhomme, Jean-Pierre Jouet, Jean-Luc Lai, Thierry Facon
Journal: Blood (2006)
Pelvic radiation with cisplatin-based chemotherapy and radiotherapy for locally advanced cervical uterine cancer.
Authors: H. R. Castro, L. Salazar
Journal: Journal of Clinical Oncology (2011)

e15578 Background: We compared the effect of radiotherapy and cisplatin-based chemotherapy in women with high-risk cervical cancer; we performed a randomized trial of pelvic radiation with two chemotherapy regimens – concurrent cisplatin alone; and concomitant neo-adjuvant cisplatin and cyclophosphamide Methods: Between 2005 and 2009, 140 women with advanced cervical cancer confined to the pelvis (stages IIB and III), were randomly assigned to receive either 50 Gy of radiation to the pelvis (group 1), received 40 mg/m2 of cisplatin per week for five weeks (group 2) and received 75 mg/m2 of cisplatin on day 1, and 400 mg/m2 of cyclophosphamide on day 1, every 28 days per four six concomitant neoadjuvant with radiotherapy (group 3). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation. Results: The analysis included 101 women. The median duration of followed was 24 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received radiotherapy alone was P: 0.022 (95 percent confidence interval, 0.026 to 0.032; 21,31 vs. 17,47 mounts ). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 2 and 3 than in group 1, with relative risk of death of 0.032 (95 percent confidence interval, 0.28 to 0.35; 31.7 mounts group 1, not yet reach the median overall survival in group 2 and 3). Conclusions: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.
OP22SIMULTANEOUS INTRA-CAVITY DELIVERY OF MULTIPLE CHEMOTHERAPEUTICS FROM A MOULDABLE NEUROSURGICALLY-APPLIED POLYMER PASTE
Authors: Toby W. Gould, Stuart J. Smith, Cheryl V. Rahman, David A. Barrett, Kevin M. Shakesheff, Richard G. Grundy, Ruman Rahman
Journal: Neuro-Oncology (2015)

INTRODUCTION: A thermo-setting biomaterial containing a depot of clinically relevant chemotherapeutics applied to the post-surgical resection cavity offers an opportunity for localised control of residual malignant glioma. Here we evaluate mouldable polymer matrices of poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) microparticles for tailored combination drug release. METHOD: Clinically-approved or experimental chemotherapeutics, alone and in combination, were loaded onto PLGA/PEG microparticle matrices, or encapsulated inside PLGA microspheres. Mono- and dual-therapy release rates were measured by liquid chromatography and stability verified by mass spectrometry. Cytotoxicity of released drugs was assessed using patient-derived invasive margin cells and flank mouse xenografts. RESULTS: Temozolomide (TMZ), etoposide (ETO) and methotrexate were released from PLGA/PEG alone or in dual combinations over 2 weeks in vitro, whilst irinotecan, cilengitide and imatinib released over a similar period as monotherapies. Cytotoxicity was not impaired by polymer interaction. Drug encapsulation in PLGA microspheres dampens the rapid burst release. PLGA/PEG overcomes TMZ instability, resulting in a 10-day release where the AIC active component was measured. In vivo ETO release markedly reduced glioma bioluminescence with longer-term survivors relative to resection-only controls. CONCLUSION: We have developed a PLGA-based platform technology to deliver multiple clinically relevant chemotherapy agents, including TMZ, from a single matrix. Prolonged release kinetics can be achieved by drug encapsulating drugs, potentially filling the 3 week therapy gap that currently exists between surgery and radiotherapy commencement.
Abstract 3635: Histone demethylase NDY1/KDM2B as a driver of survival and proliferation of normal and neoplastic mast cells
Authors: Parthena Foltopoulou, Raymond Pfau, Monica Betancur-Boissel, Manar AbdelMageed, Philip N. Tsichlis, Elizabeth A. McNiel
Journal: Cancer Research (2015)

Abstract Proliferative disorders of mast cells exhibit a range of clinical behavior from benign cutaneous forms to aggressive systemic mastocytosis and mast cell leukemia. While these disorders are rare in people, they are among the most common malignancies in the dog, a circumstance that provides a useful model for an orphan disease. Growth of both normal and neoplastic mast cells is driven by c-kit (CD117), a tyrosine kinase receptor for stem cell factor. Ligand-independent, constitutive activation of c-kit via mutation is a common feature of mastocytic neoplasia. Therefore, tyrosine kinase inhibitors (TKIs) that target c-kit have activity in aggressive mastocytosis in people and in dogs. However, resistance to c-kit targeted TKIs is common in both species, highlighting a need for other therapeutic targets. Our data indicates that chromatin modification may be important in mast cell biology. Specifically, we have shown that the JmjC domain lysine 36 specific histone H3 demethylase, NDY1/KDM2B, supports the proliferation and immortalization of bone-marrow derived mast cells. It is well known that NDY1/KDM2B is a driver of hematopoietic transformation and is associated with malignant progression in certain solid tumors (breast, pancreatic and urothelial carcinoma). Therefore, we investigated the effects of knockdown of NDY1/KDM2B in neoplastic human and canine mast cells in vitro and in xenografts. Our data demonstrate that this knockdown inhibits proliferation and induces apoptosis in vitro and inhibits tumor growth in vivo. Therefore, targeting therapy of NDY1/KDM2B or downstream effectors in mast cell tumors could be a beneficial addition to the existing therapeutic modalities. Supported by grants from the Morris Animal Foundation (D14CA) and NIH (R01CA109747). Citation Format: Parthena Foltopoulou, Raymond Pfau, Monica Betancur-Boissel, Manar AbdelMageed, Philip N. Tsichlis, Elizabeth A. McNiel. Histone demethylase NDY1/KDM2B as a driver of survival and proliferation of normal and neoplastic mast cells. [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 3635. doi:10.1158/1538-7445.AM2015-3635
Markedly Reduced Overall Survival of CYP2C19 *2/*2 Homozygotes After Myeloablative Hematopoietic Stem Cell Transplantation
Authors: Stacy E Melanson, Kristen Stevenson, Haesook T Kim, Joseph H. Antin, Vincent T Ho, Jerome Ritz, Robert J Soiffer, Michael Court, Frank Kuo, Janina Longtine, Petr Jarolim
Journal: Blood (2010)