tbuckley/cabot-search huggingface dataset:
Trough Plasma Imatinib Concentrations Are Associated with Both Cytogenetic and Molecular Responses to Standard-Dose Imatinib in Chronic Myeloid Leukemia.
Authors: Stephane Picard, Karine Titier, Gabriel Etienne, Regis Lassalle, Gerald Marit, Josy Reiffers, Bernard Begaud, Nicholas Moore, Mathieu Molimard, Francois-Xavier Mahon
Journal: Blood (2006)
The role of plasma GFAP as a biomarker for glioblastoma.
Authors: H. Husain, W. Savage, A. Everett, X. Ye, C. Blair, K. E. Romans, C. Bettegowda, P. Burger, S. A. Grossman, M. Holdhoff
Journal: Journal of Clinical Oncology (2011)

2095 Background: Magnetic resonance imaging (MRI) of the brain primarily assesses blood brain barrier (BBB) dysfunction which provides indirect information regarding tumor size. The limitations of MRI have become evident with the use of temozolomide (pseudo-progression) and VEGF based therapies (pseudo-response). As a result, a blood-based marker to assess tumor burden is increasingly important. Previous studies suggested that plasma glial fibrillary acidic protein (GFAP) levels are sensitive and specific for glioblastoma (GBM). This pilot study examines the utility of GFAP as a biomarker in pre- and post-operative gliomas. Methods: Plasma samples were collected in patients pre-operatively (N=34) and 24-48 hours post-operatively (N=24) for what was post-operatively confirmed to be newly diagnosed glioma. Plasma GFAP was detected using an electrochemiluminescent immunoassay with a detection threshold of >0.04ng/ml. Presence or absence of contrast enhancement (CE) on the pre-op MRI was compared with the pre-op plasma GFAP level using Fisher’s exact test. Results: The histologic, radiographic, and detection rates and pre- and post-op plasma GFAP levels are presented below. Higher grade tumors more often had CE on MRI than lower grade tumors (p=0.002). Plasma GFAP was detectable in 80% of patients with CE and 21% without CE (p=0.001). Conclusions: Higher grade tumors had more CE and higher plasma GFAP levels pre-operatively. However, post-operative GFAP levels dramatically increased in patients with lower grade gliomas that previously had undetectable levels. These data strongly suggest that GFAP is not a specific biomarker for GBM or an accurate measure of tumor burden. In addition, injury to the brain or BBB from surgery results in striking elevations of plasma GFAP independent of histologic grade or prior contrast enhancement. Histologic findings Contrast enhancement pre-op GFAP detectable pre-op GFAP levels pre-op median (range) GFAP detectable post-op GFAP levels post-op median (range) Grade 4 (n=9) 89% 100% 0.09 (0.07-0.15) 100% 0.07 (0.04-0.32) (N=5) Grade 3 (n=11) 55% 36% 0 (0-0.58) 100% 1.18 (0.11-4.56) (N=8) Grade 2 (n=14) 7% 21% 0 (0-0.22) 91% 0.38 (0.05-9.65) (N=11)
Pulmonary Infiltrates in a Patient With Advanced Melanoma
Authors: Charles A. Powell
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 60-year-old former smoker with metastatic melanoma presented with the chief complaint of pulmonary infiltrates. Five years ago, he was diagnosed with a left chest wall melanoma. He underwent surgery but received no additional therapy for an American Joint Committee on Cancer stage T3a N0 M0 tumor that was 2.7 mm in depth with no ulceration of the epidermal surface. Resection margins were free of tumor. Four years later, he underwent excision of a raised pigmented skin lesion on his left calf that proved to be melanoma with positive margins. He underwent re-excision of melanoma but 2 months later developed a new left hip soft tissue nodule. Positron emission tomography (PET) -computed tomography showed multiple hypermetabolic lesions involving subcutaneous tissue, muscle osseous structures, and bone marrow, consistent with advanced melanoma. He began systemic therapy with ipilimumab and nivolumab. After four cycles of immunotherapy, he developed a nonproductive cough and mild dyspnea on exertion (Modified Medical Research Council dyspnea scale score of 2 [ie, he had to stop for breath when walking at his own pace on level ground]). A chest x-ray showed bilateral hilar enlargement, thickening of the right paratracheal stripe, and scattered patchy increased interstitial markings bilaterally. PET and chest computed tomography images showed enlarged mediastinal adenopathy with increased [18F]fluorodeoxyglucose uptake on PET and scattered diffuse 1- to 2-mm pulmonary nodules with ground-glass opacities ( Fig 1 ). The patient was referred for pulmonary input. The patient had smoked one pack of cigarettes per day for 35 years; he quit 6 years ago. He had no history of pneumonia, childhood asthma, or tuberculosis. His mother had asthma, but there was no other family history of asthma or other lung disease.
Abstract 1413: Significance of KIFC1 in spheroid formation of gastric cancer cells
Authors: Naohide Oue, Shoichiro Mukai, Trang Pham T.B., Kazuhiro Sentani, Reiko Ito, Wataru Yasui
Journal: Cancer Research (2015)

Abstract Spheroid colony formation is a typically method to identify cancer stem cells (CSC). The growth of spherical colonies is considered indicative of self-renewal ability, and is consistent with a CSC phenotype. However, mechanism of spheroid formation remains unclear in gastric cancer (GC). In the present study, we analyzed spheroid formation associated genes in GC. Comprehensive gene expression profile of MKN-45 and MKN-74 GC cell lines that were grown as monolayers or spheroids was obtained by Affymetrix GeneChip, and we found several kinds of genes whose expression was up-regulated or down-regulated in cells that were grown as spheroids. Among these, 10 kinds of kinesin genes were up-regulated in both MKN-45 and MKN-74 cells that were grown as spheroids. Kinesins are categorized into 14 subfamilies and classified as mitotic kinesins, which are involved in cell division, and non-mitotic kinesins, which are principally involved in intracellular transport. In spheroids, mitotic kinesins were up-regulated. In the present study, we focused on KIFC1, because antibody against KIFC1 is available. qRT-PCR analysis revealed that up-regulation of KIFC1 in both MKN-45 and MKN-74 cells that were grown as spheroids. Immunohistochemical analysis of KIFC1 was performed in 20 GC cases. Expression of KIFC1 was up-regulated in GC tissues in comparison with corresponding non-neoplastic mucosa. These results suggest that KIFC1 plays an important role in gastric carcinogenesis and may be a therapeutic target of GC. Citation Format: Naohide Oue, Shoichiro Mukai, Trang Pham T.B., Kazuhiro Sentani, Reiko Ito, Wataru Yasui. Significance of KIFC1 in spheroid formation of gastric 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 1413. doi:10.1158/1538-7445.AM2015-1413
169. Polymer Functionalized Gold Nanoparticles in Gene Delivery In Vitro
Authors: Geraldine G. Lazarus, Neerish Revaprasadu, Moganavelli Singh
Journal: Molecular Therapy (2015)

Non-viral gene delivery approaches have been extensively studied as a basic tool for intracellular gene transfer and gene therapy especially for genetic aberrations including cancer. Gold nanoparticles have attracted strong biomedical interest for drug/gene delivery due to their low toxic nature, surface plasmon resonance and capability of increasing the stability of the payload. In the present study the synthesis of photoluminescent nanoparticles consisting of a gold core coated with polyethyleneimine, poly-L-lysine, cysteine and chitosan is reported. These functionalized gold nanoparticles (FAuNPs) were investigated at different pH values and ionic strength to identify the optimum conditions to produce stable monodisperse nanoparticles. FAuNPs showed good stability at low ionic strength which is important for the flexibility of the polymer chain. All nanoparticle/polymer formulations showed spherical particles in the size range 11.9-195 nm with narrow particle distributions and low PDI (<1.2). Nanoparticle and pDNA complexation was efficiently demonstrated in the band shift and ethidium bromide intercalation assays respectively, with serum nuclease digestion revealing partial protection of the Results: Our novel PEGylated PLGA nanoparticles (without siRNA) showed higher accumulation and extended residence time in the inflamed foot of lipopolysaccharide (LPS)-induced mouse model of chronic inflammation. TNF-α-siRNA-NPs were 176.6±15.8 nm in diameter, with a zeta potential of -25.2±2.0 mV and an entrapment efficiency of 31±4%. The nanoparticles were stable in simulated biological medium. In vitro, less than 40% of the siRNA was released with 72 h at 37oC. Finally, TNF-α-siRNA-NPs significantly decreased TNF-α release from J774A.1 cells. complexed plasmid DNA (pCMV-luc). MTT cytotoxicity experiments indicated that the FAuNPs elicited a dose dependent cytotoxic effect in four mammalian cell lines (HepG2, HEK293, HeLa and Caco2). Au-PEI/pDNA maintained over 80% cell viability across all cell lines, while the Au-cys/pDNA exhibited a significant 91.8% (p<0.001) in Caco2 cells, Au-Chit/pDNA 126% (p<0.01) in HepG2 cells and Au-PLL/pDNA 104% in Hela cells. Transfection studies were accomplished using the luciferase reporter gene assay. Results showed that the FAuNPs produced greater transgene activity than the cationic polymer/DNA complexes on their own. This was evident for the Au-PEI/pDNA complex which produced a 12 fold increase in the HEK293 cells and a 9 fold increase in the HepG2 cells, compared to the PEI/pDNA complexes. The results of this study suggest that FAuNP's low cytotoxicity coupled with the ability to parametrically control particle size and surface properties, make these nanoparticles suitable non-viral gene delivery vectors. However further engineering and modifications of the FAuNPs may be required to enable in vivo gene delivery.
BMET-38METASTASIS TO BRAIN AND LUNG IN CARCINOSARCOMA OF THE PAROTID GLAND - A CASE REPORT
Authors: Seung Ho Yang, Shan Guo, Ron Karmi, Scott Shepard, Angel Blanco, Jay-Jiguang Zhu
Journal: Neuro-Oncology (2015)

Carcinosarcoma of the parotid gland is a rare and aggressive malignant mixed tumor in which carcinomatous and sarcomatous elements coexist and they may metastasize together or independently. The tumor may occur in patients with previous or coexisting pleomorphic adenoma or may arise de novo of the parotid gland. We report a case of 56-year old male with history of carcinosarcoma of the parotid gland that subsequently developed solitary brain and lung metastases. The patient underwent craniotomy of the metastatic and symptomatic brain lesion and had adjuvant radiosurgery postoperatively. After that, his headache disappeared and the left hemiparesis improved. The next-generation sequencing gene study identified the amplification of IRS2, CDK4, IGF1R, MDM2 and MYC genes in metastatic brain lesion. In primary parotid lesion, genomic alteration identified amplification of RAF1, CDK4, IGF1R, MDM2 and MYC genes. The patient then entered a clinical trial and did not show any improvement. Due to the brain mets re-growth, a 2nd craniotomy was performed. He again improved significantly postoperatively. He currently received salvage chemotherapy for his progressive lung metastasis. The prognosis of carcinoma with distant metastasis is poor and the standard treatment has not been established yet. Herein we will present detailed pathological and molecular abnormality profiles of this case and will review similar cases reported in literatures. To our knowledge, this is the first case with carcinosarcoma of the parotid gland that developed brain and lung metastasis.
Abstract 1799: Mithramycin A as a radiation sensitizer
Authors: Bradley T. Scroggins, Jeffery F. Burkeen, Eun Joo Chung, Ayla O. White, Su I. Chung, Kathryn E. Hudak, Deborah E. Citrin
Journal: Cancer Research (2015)

Abstract Introduction: Radiation therapy (RT) is used in the treatment of many cancers to reduce or eliminate tumor burden. In many cases RT is not curative and recurrence often occurs. Therefore agents that enhance the effectiveness of RT are necessary to improve cancer management. We investigated the use of the DNA binding antibiotic mithramycin A as a radiosensitizer of solid tumors. Mithramycin A binds to GC rich regions of double stranded DNA displacing transcription factors, such as SP1. Mithramycin A has also been shown to inhibit DNA double strand break repair by mechanisms unrelated to its effect on transcription. Methods: Human cancer cells (A549/lung, HT29/colon, DU145/prostate, and UM-UC3/bladder) were grown at 37°C and 5% CO2 in RPMI1640 media. Cells were treated with 25 nM mithramycin A 1 hour prior to radiation and then allowed to grow for 7-10 days after RT. Clonogenic colonies were counted to determine the effect of mithramyicn A on radiation sensitivity. The effects of mithramycin A treatment and RT on DNA damage repair was measured by counting nuclear gamma-H2AX foci and neutral Comet assay. Cell cycle changes induced by mithramycin A and RT were measured by flow cyctometry. Mitotic catastrophe was analyzed by nuclear fragmentation. In vivo radiosensitzation of mithramycin A (1mg/kg) was quantified using growth delay of A549 tumor xenografts in both single dose (4 Gy) and fractionated RT (4x 2Gy) dosing schedules. Results: Mithramycin A treatment of cell lines in vitro prior to RT increased radiosensitivity with a range of dose modifying factors between 1.17-1.48. DNA damage repair after RT was not affected by mithramycin A treatment. Cell cycle distribution was altered by mithramycin A treatment with fewer cells in S-phase after treatment. Mitotic catastrophe after combined treatment with mithramycin A and RT was significantly elevated above the level of either agent alone. In vivo A549 tumor xenografts treated with both mithramycin A and a single dose RT had more than an additive growth delay compared to either agent alone. Conclusion: Mithramycin A treatment sensitized human cancer cells to radiation therapy in in vitro assays and an in vivo model system through an increase in mitotic catastrophe. A more detailed analysis of the mechanism of action is ongoing. Citation Format: Bradley T. Scroggins, Jeffery F. Burkeen, Eun Joo Chung, Ayla O. White, Su I. Chung, Kathryn E. Hudak, Deborah E. Citrin. Mithramycin A as a radiation sensitizer. [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 1799. doi:10.1158/1538-7445.AM2015-1799
Final Report of a Phase I Trial of Decitabine with or without hyperCVAD In Relapsed Acute Lymphocytic Leukemia (ALL)
Authors: Guillermo Garcia-Manero, Deborah A Thomas, Michael E. Rytting, Susan O'Brien, Anna R.K. Franklin, Gautam Borthakur, Monica Kwari, Sam Dara, Hui Yang, Hagop Kantarjian
Journal: Blood (2010)
Abstract 327: 3D dynamics of the response to cell cycle checkpoint targeting drugs in multicellular tumour spheroids
Authors: Valérie LOBJOIS, Odile MONDESERT, Céline FRONGIA, Annaick DESMAISON, Aurélie GOMES, Martine CAZALES, Bernard Ducommun
Journal: Cancer Research (2015)

Abstract Major recent advances have recently been made in the understanding of the molecular pathways regulating the cell cycle machinery and their deregulations in cancer. These results open new avenues for the development of innovative antitumor pharmacological strategies targeting the cell cycle and its checkpoints. MultiCellular Tumor Spheroid (MCTS) are now considered as invaluable models to study cancer cell biology and for the preclinical development of new antiproliferative drugs. To fully exploit the features of MCTS, it is essential to preserve the 3D regionalization level of analysis when investigating the effect of a drug. We will report here a breakthrough in the use of MCTS with new technological developments that can be used to explore the regionalization and the live dynamics of the effects of anticancer drugs in 3D. Spheroids expressing fluorescent cell cycle reporters (i.e. Fucci) and biosensors were engineered and used to monitor cell cycle arrest and DNA damage Response (DDR) pathway activation induced by chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated on genetically modified spheroids using innovative 3D imaging strategy (based on 3D light sheet microscopy). We will present our latest results on the characterization of the effects of several anticancer drugs including DNA damaging agents alone or in association with checkpoint abrogating compounds. This study opens new perspectives for original 3D assays dedicated to the identification of new original targets and compounds and for the investigation of the dynamics of the 3D response to novel antiproliferative agents. Citation Format: Valérie LOBJOIS, Odile MONDESERT, Céline FRONGIA, Annaick DESMAISON, Aurélie GOMES, Martine CAZALES, Bernard Ducommun. 3D dynamics of the response to cell cycle checkpoint targeting drugs in multicellular tumour spheroids. [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 327. doi:10.1158/1538-7445.AM2015-327
638. TGFBeta Signaling Blockade within PSMA Targeted CAR Human T Cells for the Eradication of Metastatic Prostate Cancer
Authors: Christopher Kloss, Jihyun Lee, Carl June
Journal: Molecular Therapy (2016)

The recent efficacies demonstrated using Chimeric Antigen Receptor (CAR) mediated immunotherapy to treat hematological malignancies have been met with great enthusiasm as holding great potential for the eradication of hematological malignancies. Unfortunately, the ability to target metastatic solid tumors like prostate cancer with CAR T cells has been less successful. The major parameter to achieve in using CAR T cells to treat prostate cancer is overcoming the immunosuppression that is created by the tumors to inhibit CAR T cells. Our efforts have aimed to create PSMA specific CAR T cells that are resistant to the TGFBeta induced suppression extensively demonstrated to exist in prostate cancer. Upon binding PSMA, our second-generation CAR supplies 4-1BB and CD3zeta signaling previously demonstrated to allow for long-term T cell persistence and eradication of leukemia when targeted to CD19. We therefore created anti-PSMA CAR T Cells that coexpress the dominant negative TGFBeta receptor II (dnTGFRBetaII). Having focused on safety and efficacy of these anti-PSMABBz CAR T cells that express dnTGFRBetaII (dnTGFRBetaII-T2A-PBBZ), we demonstrate evidence of dnTGFRBetaII functionality. The dnTGFRBetaII functions to prevent SMAD signaling induced by TGFBeta, therefore resisting upregulation of CD25 and CTLA-4 by T cells. When co-cultured with tumor cells in vitro, efficient antigen specific lysis is induced by the PBBZ CAR and the dnTGFRBetaII-T2A-PBBZ CAR T cells exhibit up to 15 fold overall proliferation than PBBZ alone CAR T cells over 42 days. This allows for superior levels of T cell persistence in the peripheral blood of NSG mice after 3-4 weeks post infusion when compared to T cells expressing the anti-PSMA CAR alone. Most importantly, these CAR T cells are very effective at eradicating systemic PSMA+ PC3 prostate cancer cells in vivo demonstrated in two animal experiments at three different doses of CAR T cells. These studies suggest proper resistance to TGFBeta by CAR modified T cells that show great promise to eradicate metastatic prostate cancer in the clinic. Disclosure of Conflict of Interest: C.C.K. reports having ownership interest in patents owned by Memorial Sloan-Kettering Cancer Center and licensed to Juno Therapeutics and is a consultant for 121 Bio, LLC. J.L. reports no conflicts. C.H.J. reports receiving commercial research grants from Novartis and has ownership interest in patents owned by University of Pennsylvania and licensed to Novartis. Funding Acknowledgments: This study was supported by the Prostate Cancer Foundation All-Star Killer T-Cell Special Challenge Award 2014 - 2016.
Brain-computer interface for the communication of acute patients: a feasibility study and a randomized controlled trial comparing performance with healthy participants and a traditional assistive device
Authors: Louis Mayaud, Salvador Cabanilles, Aurélien Van Langhenhove, Marco Congedo, Alexandre Barachant, Samuel Pouplin, Sabine Filipe, Lucie Pétégnief, Olivier Rochecouste, Eric Azabou, Caroline Hugeron, Michèle Lejaille, David Orlikowski, Djillali Annane
Journal: Brain-Computer Interfaces (2016)

This study presents the outcome of the 5-year-long French national project aiming at the development and evaluation of an effective brain-computer interface (BCI) prototype for the communication of patients with acute motor disabilities. It presents results from two clinical studies: a clinical feasibility study carried out partly in the intensive care unit (ICU) and the clinical evaluation of an innovative BCI prototype. In this second study the BCI performance of patients was compared to that of healthy volunteers and benchmarked against a traditional assistive technology (scanning device). Altogether, 15 of 22 patients could control the BCI system with an accuracy significantly above the chance level. The bit-rate of the traditional assistive technology proved superior, even though an equivalent bit-rate could be achieved using personalized parameters for the BCI. Fatigue was found to be the primary limitation factor, which was particularly true for patients and during the use of the BCI. A classifier based on Riemannian geometry was found to contribute significantly to the accuracy of the BCI system. This study demonstrates that the communication of patients with severe motor impairments can be effectively restored using an adequately designed BCI system. All electrophysiological data are freely available at the Physionet.org platform.
Integration of medical oncology and palliative care to improve the appropriateness of antitumor therapy near the end of life in advanced cancer patients: first evidences of the prospective sequential MIRTO study. (Supported by “Programma di Ricerca Regione Emilia-Romagna-Università 2007-2009 Area 2 - Ricerca per il Governo clinico”)
Authors: A. Martoni, B. Melotti, C. Degli Esposti, G. Lelli, V. Mutri, D. Corrado, S. Ansaloni, F. Pannuti, E. Strocchi, A. Ardizzoni
Journal: Annals of Oncology (2015)
Stromal Cross-Presentation and Host Interferon-γ Signaling and Are Required for Elimination of Antigen-Loss Variants of High-Grade B Cell Lymphomas: Implications for Adoptive T Cell Therapy
Authors: Armin Gerbitz, Madhusudhanan Sukumar, Florian Helm, Andrea Wilke, Christian Friese, Cornelia Fahrenwaldt, Frank Lehmann, Christoph Loddenkemper, Thomas Kammertöns, Josef Mautner, Thomas Blankenstein, Georg Bornkamm
Journal: Blood (2010)
Identification of Putative New Tumor Suppressor Genes in Highly Purified CD34+ Bone Marrow Cells from Patients with Myelodysplastic Syndromes.
Authors: Saskia Gueller, Martina Komor, Julian C. Desmond, Oliver G. Ottmann, Dieter Hoelzer, H. Phillip Koeffler, Wolf-Karsten Hofmann
Journal: Blood (2004)
Abstract 18036: Exosomes From Human CD34+ Cells Mediate Angiogenic Effects in vitro and in vivo
Authors: Susmita Sahoo, Tina Thorne, Sol Misener, Meredith Millay, Ting Liu, Aiko Ito, James Marvin, Ekaterina Klyachko, Douglas W Losordo
Journal: Circulation (2010)

In preclinical studies and early phase clinical trials, CD34+ cells have been shown to induce neovascularization in ischemic tissue, improving perfusion and function. Several reports have suggested...