tbuckley/cabot-search huggingface dataset:
Patient-reported symptoms from patients with advanced pancreatic cancer undergoing gemcitabine-based chemotherapy.
Authors: Xin Shelley Wang, David R. Fogelman, Qiuling Shi, Cathy Eng, Raza H Bokhari, Furong Huang, Gary M. Mobley, Katherine R. Gilmore, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

370 Background: The symptoms reported by patients being treated for advanced pancreatic cancer (PC) could be driven by disease and treatment. Few clinical studies have addressed the interaction between disease, treatment, and symptom burden. We conducted a longitudinal study tracking multiple symptoms to provide an evidence-based symptom profile for patients with advanced PC receiving gemcitabine-based chemotherapy. Methods: From start of the first chemotherapy cycle (baseline), patients rated symptoms weekly during chemotherapy via the M. D. Anderson Symptom Inventory (MDASI), then continued symptom assessment every two weeks for up to 40 weeks. Longitudinal symptom responses were analyzed by mixed-effect modeling. Results: Among 100 PC patients enrolled, 87% were treatment-naïve. The median age was 65 yrs old (range 35-85). Half of the sample was female; 32% received opioids for severe pain. The three most severe MDASI symptoms at baseline were fatigue, lack of appetite, and pain. Poor performance status and opioid use were significantly related to severity of these baseline symptoms (all P&lt;.05%). The marginal means of severity for these three symptoms were significantly higher over time in patients who discontinued therapy &lt; 9 weeks, compared with those who remained on study for 26-40 weeks (fatigue, P=.028; lack of appetite, P=.012; pain, P&lt;.0001). Over time, lack of appetite improved significantly (P=.039), while pain and fatigue tended to worsen (P=NS). Compared with patients who remained on study, patients discontinued treatment earlier had significantly worse baseline pain (P=.005) and a non-significant trend towards greater fatigue and lack of appetite. Conclusions: Our results suggest that standard gemcitabine-based chemotherapy plus active palliative care for advanced PC was associated with significant improvement in appetite. However, worsening fatigue suggests a need to provide active intervention to minimize this symptom for PC patients. Patients suffering from greater symptom burden at baseline and overtime, seems consistent with greater disease burden, may be expected to discontinue treatment earlier.
Study of the Relation Between the Time Course of the JAK2V617F Allele Burden and the Clinical Evolution in Patients with Myeloproliferative Neoplasms (MPN); A Single Center Study
Authors: Marta Anna Sobas, Manuel Pérez-Encinas, Celsa Quinteiro, Teresa González, Sandra Suaréz, Natalia Alonso, José Díaz, Angeles Bendaña, Marta Sonia González, Jose-Luis Bello
Journal: Blood (2008)
Somatic Fas Mutations Account for Nearly One Third of Autoimmune Lymphoproliferative Syndrome (ALPS) Cases with Previously Unknown Genetic Mutations.
Authors: Kennichi Dowdell, Julie Niemela, Susan Price, Joie Davis, Katie Perkins, Janet Dale, Jennifer M. Puck, Joao Bosco Oliveira, Jeffrey Cohen, Thomas Fleisher, V. Koneti Rao
Journal: Blood (2009)
Chemotherapy, Genetic Susceptibility, and Risk of Venous Thromboembolism in Breast Cancer Patients
Authors: Judith S. Brand, Elham Hedayati, Keith Humphreys, Jonas F. Ludvigsson, Anna L.V. Johansson, Jonas Bergh, Per Hall, Kamila Czene
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental Design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan–Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40–2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24–2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P &amp;lt; 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer. Clin Cancer Res; 22(21); 5249–55. ©2016 AACR.
Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study
Authors: Eline H. van den Berg, Lynnda J.N. van Tienhoven-Wind, Marzyeh Amini, Tim C.M.A. Schreuder, Klaas Nico Faber, Hans Blokzijl, Robin P.F. Dullaart
Journal: Metabolism (2016)
Cost-Effectiveness Evaluation for the US of Fondaparinux Compared to Argatroban in the Management of Suspected HIT
Authors: Ahmed Aljabri, Mahdi Gharaibeh, Yvonne Huckleberry, Hussam Kutbi, Yuval Raz, Seongseok Yun, Ivo Abraham, Brian Erstad
Journal: Blood (2015)
Abstract 1538: Levels and enzyme activity of CD73 in primary samples from cancer patients
Authors: Qihui Huang, Nicholas M. Durham, Erin Sult, Yuling Wu, Jenny Liu, Nicholas Holoweckyj, Laurie Iciek, Robert Hollingsworth, Brett Hall, Ronald Herbst, Ching Ching Leow, Kris Sachsenmeier
Journal: Cancer Research (2015)

Abstract CD73 is an ectonucleotidase that converts extracellular AMP to Adenosine. Within the tumor microenvironment, adenosine produced by CD73 is believed to have an immunosuppressive effect upon anti-tumor immunity. CD73 is found on lymphoid and myeloid cells, and blockade of this enzyme has been shown to alter the suppressive capacity of cells. Expression of surface CD73 as well as soluble CD73(sCD73) levels were measured in serum, peripheral blood mononuclear cells, and tumor samples from healthy and cancer patient donors. Enzymatic activity of both surface CD73 and sCD73 was determined and differences in levels across varying tumor types and disease status were quantified. In addition, CD73 levels and activity were measured after incubation or treatment with anti-CD73 antibody, MEDI9447. These studies suggest a potential role of surface and sCD73 as a pharmacodynamic and/ or predictive biomarker of anti-CD73 immunotherapy. Citation Format: Qihui Huang, Nicholas M. Durham, Erin Sult, Yuling Wu, Jenny Liu, Nicholas Holoweckyj, Laurie Iciek, Robert Hollingsworth, Brett Hall, Ronald Herbst, Ching Ching Leow, Kris Sachsenmeier. Levels and enzyme activity of CD73 in primary samples from cancer patients. [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 1538. doi:10.1158/1538-7445.AM2015-1538
Higher-Dose Imatinib (600 mg/Day) with Selective Intensification in Newly Diagnosed CML Patients in Chronic Phase; Cytogenetic Response Rates at 12 Months Are Superior to IRIS.
Authors: Timothy Hughes, S. Branford, J. Reynolds, J. Seymour, K. Taylor, N. Guzzo-Pernell, R. Filshie, C. Arthur, A. Schwarer, M. Hertzberg, Z. Rudzki, M. Copeman, K. Lynch, A. Grigg
Journal: Blood (2004)
Identification of Differentially Expressed Proteins from the Mitochondria Enriched Cytoplasmic Fractions in Primary AML Cells.
Authors: Myung-Geun Shin, Hye-Ran Kim, Hyeoung-Joon Kim, Il-Kwon Lee, Mi-Ji Kim, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang
Journal: Blood (2007)
Prognostic Impact of Molecular Mutations in AML at First Relapse
Authors: Anjali S. Advani, Paul Elson, Valeria Visconte, Jennifer S. Carew, Jaime Fensterl, Bartlomiej Przychodzen, Mikkael A. Sekeres, Cassandra M Hirsch, Alek Nielsen, John Desamito, Hetty E. Carraway, Aaron T. Gerds, Betty K. Hamilton, Sudipto Mukherjee, Ronald M. Sobecks, Matt Kalaycio, Yogen Saunthararajah, Jaroslaw P. Maciejewski
Journal: Blood (2015)
Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure
Authors: Alberto Aimo, Giuseppe Vergaro, Claudio Passino, Andrea Ripoli, Bonnie Ky, Wayne L. Miller, Antoni Bayes-Genis, Inder Anand, James L. Januzzi, Michele Emdin
Journal: JACC Heart Failure (2016)
Bone Marrow Hypocellularity Does Not Impair the Tolerability or Efficacy of Azacitidine (AZA) in Patients with Higher-Risk Myelodysplastic Syndromes Treated in the AZA-001 Study
Authors: John F Seymour, John M. Bennett, Alan F List, Ghulam J. Mufti, Steven D. Gore, Pierre Fenaux, Valeria Santini, Joel Hetzer, Stephen Songer, Barry S. Skikne, C.L. Beach
Journal: Blood (2012)
CBM-04PD-1 EXPRESSION IDENTIFIES EXHAUSTED TUMOR INFILTRATING REGULATORY T CELLS IN GLIOBLASTOMA
Authors: Liliana Lucca, Brittany A. Goods, Daniel E. Lowther, Amanda Hernandez, Benjamin Lerner, Murat Gunel, Khadir Raddassi, Jason Simon, Robert Latek, Vlad Coric, J. Christopher Love, David A. Hafler
Journal: Neuro-Oncology (2015)

BACKGROUND: Foxp3+ regulatory T cells (Tregs) are central in ensuring protective immune responses while preventing immunopathology. While Tregs exhibit defective function in autoimmune disorders, they appear to be enriched in tumor immune infiltrates, suggesting a role in failure of immune-mediated tumor rejection. Tumor-infiltrating Tregs express higher levels of the co-inhibitory receptor PD-1 compared to circulating Tregs, especially in patients with glioblastoma. PD-1 is overexpressed by effector T cells in chronic immune responses and plays a pivotal role in driving T cell exhaustion in these conditions. METHODS: We examined the phenotype and function of CD4+CD25+CD127−Foxp3+ Tregs from peripheral blood and tumor infiltrates of patients with different grades of glioma, including glioblastoma (n = 20). Assessments included functional evaluation of Tregs in co-culture suppression assays with blood-derived T effector cells, and transcriptional profiling by RNA sequencing. RESULTS: By comparing the functionality of Tregs derived from blood and tumors of patients with glioblastoma, we established increased Treg expression of PD-1 is associated with impaired suppressive function and production of proinflammatory cytokines. Transcriptional profiling of PD-1+ Tregs revealed tumor-infiltrating PD-1+ Tregs are enriched for several exhaustion signatures, confirming PD-1 is a marker of exhaustion not only for effector T cells but also for Tregs. Finally, we investigated phenotype and function of PD-1+ Tregs in the circulation of healthy individuals (no known history of cancer, autoimmune disease, or other inflammatory conditions), and observed a similar loss of suppressive function and an exhausted transcriptional profile. CONCLUSIONS: Expression of PD-1 marks a population of dysfunctional Tregs that occurs in normal immunity and is enriched in cancer, specifically in the tumor. That Tregs from the tumor fail to suppress effector immune responses suggests that loss of effector T-cell function is more likely to result from chronic stimulation by the tumor than from active regulation by Tregs.
Active oxygenation of University of Wisconsin solution for cold storage restores cellular energy levels of human bile ducts from donors after brain-dead donation but not after circulatory death
Authors: Pepijn D. Weeder, Sanna op den Dries, Paulo N. Martins, Bote G. Bruinsma, James F. Markmann, Heidi Yeh, Robert J. Porte, Korkut Uygun
Journal: Hepatology (2014)
Early Results from a Phase II Study of Lenalidomide Monotherapy in Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma.
Authors: Thomas E. Witzig, Julie M. Vose, Henry P. Kaplan, Jeffrey Lee Wolf, Dennis Pietronigro, Kenichi Takeshita, Annette Ervin-Haynes, Jerome B. Zeldis, Peter H. Wiernik
Journal: Blood (2006)
CLL Cell Viability Promoted by Myosin Heavy Chain IIA Exposed Apoptotic Cells is BTK-dependent
Authors: Charles C. Chu, Lu Zhang, Xiaoxuan Cui, Amanda R. Magli, Xiao-Jie Yan, Jonathan E. Kolitz, Steven L. Allen, Jacqueline C. Barrientos, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2012)
Successful Bone Marrow Transplantation with an Intensively Immunosuppressive Conditioning with Low Toxicity for High-Risk Chronic Granulomatous Disease Patients.
Authors: Mizuka Miki, Teruyuki Kajiume, Kazuhiro Nakamura, Hiroshi Kawaguchi, Takashi Sato, Emi Kurita, Rie Onodera, Asako Hiraoka, Tomoyuki Mizukami, Hiroyuki Nunoi, Masao Kobayashi
Journal: Blood (2006)
G13 : Ombitasvir/paritaprevir/ritonavir for treatment of HCV genotype 1b in Japanese patients with or without cirrhosis: Results from gift-I
Authors: K. Chayama, F. Suzuki, K. Ikeda, H. Toyoda, K. Sato, Y. Karino, Y. Matsuzaki, K. Kioka, T. Pilot-Matias, C. Setze, X. Zhang, P. Badri, T. Yanke, T. Matsuda, R.A. Vilchez, L. Rodrigues-Jr, H. Kumada
Journal: Journal of Hepatology (2015)
Cross-Talk Between Tumor B Cells, Follicular Dendritic Cells, and Follicular Helper T Cells: Implications for Follicular Lymphoma Pathogenesis and Therapy,
Authors: Shibichakravarthy Kannan, Fuliang Chu, Seema Rawal, Myriam Foglietta, David Delgado, Sattva S. Neelapu
Journal: Blood (2011)
Standard R-CHOP Therapy in Follicular Lymphoma and Diffuse Large B-Cell Lymphoma
Authors: Naoto Tomita, Hirotaka Takasaki, Shin Fujisawa, Kazuho Miyashita, Eriko Ogusa, Kumiko Kishimoto, Shiro Matsuura, Rika Sakai, Hideyuki Koharazawa, Wataru Yamamoto, Katsumichi Fujimaki, Hiroyuki Fujita, Yoshimi Yamamoto, Jun Taguchi, Hideyuki Kuwabara, Shigeki Motomura, Yoshiaki Ishigatsubo
Journal: Blood (2011)
Neonatal Cord Blood Oxylipins and Exposure to Particulate Matter in the Early-Life Environment: An ENVIR <i>ON</i> AGE Birth Cohort Study
Authors: Dries S. Martens, Sandra Gouveia, Narjes Madhloum, Bram G. Janssen, Michelle Plusquin, Charlotte Vanpoucke, Wouter Lefebvre, Bertil Forsberg, Malin Nording, Tim S. Nawrot
Journal: Environmental Health Perspectives (2016)

As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acids. Oxylipins could provide a new target in the developmental origins model or the ability of early life exposure to change biology.We studied the association between in utero PM2.5 (particulate matter with aerodynamic diameter < 2.5 μm) exposure and oxylipin profiles in newborns.Thirty-seven oxylipins reflecting the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) pathways were assayed in 197 cord blood plasma samples from the ENVIRONAGE birth cohort. Principal component (PC) analysis and multiple regression models were used to estimate associations of in utero PM2.5 exposure with oxylipin pathways and individual metabolites.A principal component representing the 5-LOX pathway (6 metabolites) was significantly positively associated with PM2.5 exposure during the entire (multiple testing-adjusted q-value = 0.05) and second trimester of pregnancy (q = 0.05). A principal component representing the 12/15-LOX pathway (11 metabolites) was positively associated with PM2.5 exposure during the second trimester of pregnancy (q = 0.05). PM2.5 was not significantly associated with the COX pathway during any time period. There was a positive but nonsignificant association between second-trimester PM2.5 and the CYP pathway (q = 0.16).In utero exposure to particulate matter, particularly during the second trimester, was associated with differences in the cord blood levels of metabolites derived from the lipoxygenase pathways. These differences may indicate an effect of air pollution during in utero life on the inflammatory state of the newborn at birth. Oxylipins may be important mediators between early life exposures and health outcomes later in life.
Phase II Trial In Advanced Waldenstrom Macroglobulinemia (WM) Patients With Bortezomib: Interest Of Addition Of Dexamethasone To Bortezomib On Behalf Of The French CLL/WM Intergroup (NCT 00777738)
Authors: Veronique Leblond, Sylvie Chevret, marie Sarah Dilhuydy, Xavier Leleu, Carole Soussain, Stéphane Leprêtre, Brigitte Dreyfus, Caroline Dartigeas, Beatrice Mahe, Bruno Anglaret, Brigitte Pegourie, Caroline Besson, Therese Aurran, Anne Vekhoff, Olivier Tournilhac, Anne Banos, Herve Oya, Julie Lejeune, Pierre Morel
Journal: Blood (2013)
Association Of Bleeding Tendency With Time Under Target FIX Activity Levels In Severe Hemophilia B Patients Treated With Recombinant Factor IX Fc Fusion Protein
Authors: Amy Shapiro, James Potts, Shuanglian Li, Leonard A. Valentino, Lei Diao, Ping Wang, Brian Robinson, Glenn F Pierce, Haiyan Jiang
Journal: Blood (2013)
High Event-Free Survival Rate with Minimum-Dose-Anthracycline Treatment in Childhood Acute Promyelocytic Leukemia: A Nationwide Prospective Study By the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG)
Authors: Hiroyuki Takahashi, Tomoyuki Watanabe, Akitoshi Kinoshita, Yuki Yuza, Hiroshi Moritake, Kiminori Terui, Shotaro Iwamoto, Hideki Nakayama, Akira Shimada, Kazuko Kudo, Tomohiko Taki, Miharu Yabe, Hiromichi Matsushita, Yuka Yamashita, Kazutoshi Koike, Atsushi Ogawa, Yoshiyuki Kosaka, Daisuke Tomizawa, Takashi Taga, Akiko M. Saito, Keizo Horibe, Tatsutoshi Nakahata, Hayato Miyachi, Akio Tawa, Souichi Adachi
Journal: Blood (2014)
Tanespimycin + Bortezomib in Relapsed/Refractory Myeloma Patients: Results From the Time-2 Study.
Authors: Ashraf Z. Badros, Paul G. Richardson, Maher Albitar, Sundar Jagannath, Stefano Tarantolo, Jeffrey L. Wolf, Marianne Messina, David Berman, Kenneth C. Anderson
Journal: Blood (2009)
Functional defect of variants in the adenosine triphosphate–binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX‐770)
Authors: Jean‐Louis Delaunay, Alix Bruneau, Brice Hoffmann, Anne‐Marie Durand‐Schneider, Véronique Barbu, Emmanuel Jacquemin, Michèle Maurice, Chantal Housset, Isabelle Callebaut, Tounsia Aït‐Slimane
Journal: Hepatology (2016)

ABCB4 (MDR3) is an adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding. Five disease‐causing variations in these motifs have been identified in ABCB4 (G535D, G536R, S1076C, S1176L, and G1178S), three of which are homologous to the gating mutations of cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7; i.e., G551D, S1251N, and G1349D), that were previously shown to be function defective and corrected by ivacaftor (VX‐770; Kalydeco), a clinically approved CFTR potentiator. Three‐dimensional structural modeling predicted that all five ABCB4 variants would disrupt critical interactions in the binding of ATP and thereby impair ATP‐induced nucleotide‐binding domain dimerization and ABCB4 function. This prediction was confirmed by expression in cell models, which showed that the ABCB4 mutants were normally processed and targeted to the plasma membrane, whereas their PC secretion activity was dramatically decreased. As also hypothesized on the basis of molecular modeling, PC secretion activity of the mutants was rescued by the CFTR potentiator, ivacaftor (VX‐770). Conclusion : Disease‐causing variations in the ATP‐binding sites of ABCB4 cause defects in PC secretion, which can be rescued by ivacaftor. These results provide the first experimental evidence that ivacaftor is a potential therapy for selected patients who harbor mutations in the ATP‐binding sites of ABCB4. (H epatology 2017;65:560‐570)
New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective
Authors: Benedetta Allegranzi, Peter Bischoff, Stijn de Jonge, N Zeynep Kubilay, Bassim Zayed, Stacey M Gomes, Mohamed Abbas, Jasper J Atema, Sarah Gans, Miranda van Rijen, Marja A Boermeester, Matthias Egger, Jan Kluytmans, Didier Pittet, Joseph S Solomkin
Journal: The Lancet Infectious Diseases (2016)
FOG-1 Directly Binds to a Chromatin Remodeling and Deacetylase-Containing Complex To Mediate Transcriptional Repression by GATA-1.
Authors: Wei Hong, Minako Nakazawa, Ying-Yu Chen, Rajashree Kori, Carrie Rakowski, Gerd A. Blobel Md
Journal: Blood (2004)
Mutations in the Exon 12 of the JAK2 Gene Appeared To Be a Rare Event Essentially Clustered in V617F JAK2 Negative PV Patients.
Authors: Eirini Kouroupi, Nathalie Parquet, Christine Zoi, Jean-Jacques Kiladjian, Vassiliki Grigoraki, Katerina Zoi, Linda Scott, Christine Dosquet, Pierre Fenaux, Dimitris Loukopoulos, Christine Chomienne, Bruno Cassinat
Journal: Blood (2007)
Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells
Authors: Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Giulia Mesiano, Ramona Rotolo, Francesco Sassi, Martina Sanlorenzo, Alessandro Zaccagna, Alberto Pisacane, Rebecca Senetta, Michela Cangemi, Giulia Cattaneo, Valentina Martin, Valentina Coha, Susanna Gallo, Ymera Pignochino, Anna Sapino, Giovanni Grignani, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
Journal: Clinical Cancer Research (2016)

Purpose: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses.Experimental Design: Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter oct4 Their stemness potential was confirmed in vivo by limiting dilution assays. We explored the sensitivity of eGFP+ mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, in vitro First, we treated MCs in vitro with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells. CIK cell activity against chemoresistant mCSCs was confirmed in vivo in two distinct immunodeficient murine models.Results: We visualized eGFP+ mCSCs (14% ± 2.1%) in 11 MCs. The tumorigenic precursor rate in vivo was higher within eGFP+ MCs (1/42) compared with the eGFP- counterpart (1/4,870). In vitro mCSCs were relatively resistant to CHT and BRAFi, but killed by CIK cells (n = 11, 8/11 autologous), with specific lysis ranging from 95% [effector:tumor ratio (E:T), 40:1] to 20% (E:T 1:3). In vivo infusion of autologous CIK cells into mice bearing xenografts from three distinct melanomas demonstrated significant tumor responses involving CHT-spared eGFP+ mCSCs (P = 0.001). Sequential CHT-immunotherapy treatment retained antitumor activity (n = 12, P = 0.001) reducing mCSC rates (P = 0.01).Conclusions: These findings are the first demonstration that immunotherapy with CIK cells is active against autologous mCSCs surviving CHT or BRAFi. An experimental platform for mCSC study and rationale for CIK cells in melanoma clinical study is provided. Clin Cancer Res; 23(9); 2277-88. ©2016 AACR.
Increased NK Cells and Decreased CD3+CD8+CD62L+ T Cells in CML Patients Who Sustained Complete Molecular Remission After Discontinuation of Imatinib
Authors: Kazuma Ohyashiki, Sei-ichiro Katagiri, Tetsuzo Tauchi, Junko H Ohyashiki, Yasuhiro Maeda, Itaru Matsumura, Taiichi Kyo
Journal: Blood (2011)