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  1. Book ; Online ; E-Book: Strategies to enhance the therapeutic ratio of radiation as a cancer treatment

    Anscher, Mitchell S. / Valerie, Kristoffer

    2016  

    Author's details Mitchell S. Anscher, Kristoffer Valerie editors
    Keywords Bioactive Drugs ; Normal Tissues ; Radiation ; Therapeutic Ratio ; Tumor
    Language English
    Size 1 Online-Ressource (vi, 305 Seiten), Illustrationen, Diagramme
    Publisher Springer
    Publishing place Cham
    Publishing country Switzerland
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT019152910
    ISBN 978-3-319-45594-5 ; 9783319455921 ; 3-319-45594-X ; 3319455923
    DOI 10.1007/978-3-319-45594-5
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: Commissioning and Assessment of Radiation Field and Dose Inhomogeneity for a Dual X-ray Tube Cabinet Irradiator: To Ensure Accurate Dosimetry in Radiation Biology Experiments.

    Polizzi, Mitchell / Valerie, Kristoffer / Kim, Siyong

    Advances in radiation oncology

    2024  Volume 9, Issue 6, Page(s) 101486

    Abstract: Purpose: Standardization of x-ray cabinet irradiator dose, geometry, and calibration reporting is an ongoing process. Multi-tube designs have been introduced into the preclinical market and give a theoretical benefit but have not been widely assessed ... ...

    Abstract Purpose: Standardization of x-ray cabinet irradiator dose, geometry, and calibration reporting is an ongoing process. Multi-tube designs have been introduced into the preclinical market and give a theoretical benefit but have not been widely assessed for use in preclinical irradiation conditions. The aim of this study was to report our experience commissioning a dual x-ray source cabinet irradiator (CIXD, Xstrahl Limited, United Kingdom) and assess the dose distribution for various experimental conditions.
    Methods and materials: Half-value layer (HVL) measurement, profile measurements, and output calibration were performed using a calibrated ion chamber. Constancy measurements were performed twice daily over 2 weeks to assess output fluctuations. Film measurements were completed using solid water to assess percent depth dose and homogeneity within the field and within variable thicknesses of solid water and phosphate-buffered saline solution. Film measurements were repeated for various arrangements of petri dishes filled with phosphate-buffered saline or water and in a 3D-printed mouse phantom.
    Results: The x-ray tubes had a measured in-air output of 1.27 Gy/min. The HVL was 1.7 mm Cu. The upper and lower tubes both exhibited the heel effect, but when operated simultaneously, the effect was reduced. Ion chamber measurements revealed a 15% dose inhomogeneity within the tray area (18 × 18 cm
    Conclusions: X-ray cell culture and animal irradiation with dual tube cabinet irradiation is efficient and robust when using established dosimetric tools to confirm output and homogeneity. The conditions assumed for calibrations are often not maintained during experiments. We have confirmed that inhomogeneities are present for single-tube use; however, they are reduced with simultaneous tube use. Additional dosimetric monitoring should be performed for each unique irradiation setup.
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Journal Article
    ISSN 2452-1094
    ISSN 2452-1094
    DOI 10.1016/j.adro.2024.101486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lymph node-targeting adjuvant/neoantigen-codelivering vaccines for combination glioblastoma radioimmunotherapy.

    Su, Ting / Zhou, Shurong / Yang, Suling / Humble, Nicholas / Zhang, Fuwu / Yu, Guocan / Bos, Paula D / Cheng, Furong / Valerie, Kristoffer / Zhu, Guizhi

    Theranostics

    2023  Volume 13, Issue 13, Page(s) 4304–4315

    Abstract: Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. ... ...

    Abstract Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. Immunotherapy, such as immune checkpoint blockade (ICB), has thus far shown limited clinical benefit for GBM patients. Therapeutic vaccines hold great potential to elicit anti-cancer adaptive immunity, which can be synergistically combined with ICB and radiotherapy. Peptide vaccines are attractive for their ease of manufacturing and stability, but their therapeutic efficacy has been limited due to poor vaccine co-delivery and the limited ability of monovalent antigen vaccines to prevent tumor immune evasion. To address these challenges, here, we report GBM radioimmunotherapy that combines radiotherapy, ICB, and multivalent lymph-node-targeting adjuvant/antigen-codelivering albumin-binding vaccines (AAco-AlbiVax). Specifically, to codeliver peptide neoantigens and adjuvant CpG to lymph nodes (LNs), we developed AAco-AlbiVax based on a Y-shaped DNA scaffold that was site-specifically conjugated with CpG, peptide neoantigens, and albumin-binding maleimide-modified Evans blue derivative (MEB). As a result, these vaccines elicited antitumor immunity including neoantigen-specific CD8
    MeSH term(s) Animals ; Mice ; Glioblastoma/radiotherapy ; Radioimmunotherapy ; Neoplasm Recurrence, Local ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Vaccines ; Albumins ; Lymph Nodes
    Chemical Substances Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Vaccines ; Albumins
    Language English
    Publishing date 2023-08-06
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.84443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The preoperative G8 geriatric screening tool independently predicts survival in older patients with endometrial cancer: results of a retrospective single-institution cohort study

    Anic, Katharina / Altehoefer, Christin / Krajnak, Slavomir / Schmidt, Mona Wanda / Schwab, Roxana / Linz, Valerie Catherine / Schmidt, Marcus / Westphalen, Christiane / Hartmann, Erik Kristoffer / Hasenburg, Annette / Battista, Marco Johannes

    J Cancer Res Clin Oncol. 2023 Feb., v. 149, no. 2, p. 851-863

    2023  , Page(s) 851–863

    Abstract: PURPOSE: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival. METHODS: Preoperative frailty status was assessed by the G8 ... ...

    Abstract PURPOSE: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival. METHODS: Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan–Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters. RESULTS: 153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35–15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31–6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively). CONCLUSIONS: This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity.
    Keywords cohort studies ; comorbidity ; decision making ; elderly ; health status ; histopathology ; lifestyle ; medical facilities ; morbidity ; retrospective studies ; risk ; uterine neoplasms
    Language English
    Dates of publication 2023-02
    Size p. 851-863
    Publishing place Springer Berlin Heidelberg
    Document type Article ; Online
    ZDB-ID 134792-5
    ISSN 1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
    ISSN (online) 1432-1335
    ISSN 0171-5216 ; 0084-5353 ; 0943-9382
    DOI 10.1007/s00432-022-03934-1
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 61/57: Show issues

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  5. Article ; Online: DNA Damage Response in Human Stem Cells and Neural Descendants.

    Beckta, Jason M / Adams, Bret R / Valerie, Kristoffer

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1599, Page(s) 375–390

    Abstract: Glial cells are crucial for the normal function of neurons and are intricately involved in the pathogenesis of neurodegenerative diseases as well as neurologic malignancies. A deeper understanding of the mechanisms by which glial cells influence the ... ...

    Abstract Glial cells are crucial for the normal function of neurons and are intricately involved in the pathogenesis of neurodegenerative diseases as well as neurologic malignancies. A deeper understanding of the mechanisms by which glial cells influence the development of such pathologies will undoubtedly lead to new and improved therapeutic approaches. Commercially available human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), both of which can be differentiated into neural progenitors (NPs) and various neural cell lineages, have become widely used as sources for producing normal human central nervous system (CNS) cells. A better understanding of the DNA damage response (DDR) that occurs in these cells after therapeutic ionizing radiation (IR) and chemotherapy is essential for assessing the effects on healthy human brain.Neurodegenerative features associated with conditions such as ataxia telangiectasia and Nijmegen breakage syndrome highlight the importance of DNA double strand break (DSB) repair pathways in maintaining genomic integrity in cells of the CNS. Similarly, the development of brain tumors is also intricately linked to DNA repair. The importance of ATM and the other phosphatidylinositol 3-kinase-related kinase (PIKK) family members, ATR and DNA-PKcs, is not fully defined in either CNS developmental or pathological states. While their roles are relatively well established in the DDR of proliferating cells, our recent work has demonstrated that these processes exhibit spatiotemporal evolution during cell differentiation. This chapter discusses and explores various laboratory techniques for investigating the role of ATM in hESCs and differentiated neural cells.
    MeSH term(s) Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; DNA Breaks, Double-Stranded ; DNA Damage/genetics ; DNA Damage/physiology ; DNA Repair/genetics ; DNA Repair/physiology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Humans ; Stem Cells/cytology ; Stem Cells/metabolism
    Chemical Substances Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1)
    Language English
    Publishing date 2017-03-17
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-6955-5_27
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Editor's Note:

    Boukerche, Habib / Su, Zao-Zhong / Emdad, Luni / Baril, Patrick / Balme, Brigitte / Thomas, Luc / Randolph, Aaron / Valerie, Kristoffer / Sarkar, Devanand / Fisher, Paul B

    Cancer research

    2019  Volume 79, Issue 19, Page(s) 5127

    Language English
    Publishing date 2019-09-30
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-19-2443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  7. Article ; Online: STING activation in cancer immunotherapy.

    Su, Ting / Zhang, Yu / Valerie, Kristoffer / Wang, Xiang-Yang / Lin, Shuibin / Zhu, Guizhi

    Theranostics

    2019  Volume 9, Issue 25, Page(s) 7759–7771

    Abstract: Cancer immunotherapy modulates and leverages the host immune system to treat cancer. The past decade has witnessed historical advancement of cancer immunotherapy. A myriad of approaches have been explored to elicit or augment anticancer innate immunity ... ...

    Abstract Cancer immunotherapy modulates and leverages the host immune system to treat cancer. The past decade has witnessed historical advancement of cancer immunotherapy. A myriad of approaches have been explored to elicit or augment anticancer innate immunity and/or adaptive immunity. Recently, activation of stimulator of interferon (IFN) genes (STING), an intracellular receptor residing in the endoplasmic reticulum, has shown great potential to enhance antitumor immunity through the induction of a variety of pro-inflammatory cytokines and chemokines, including type I IFNs. A number of natural and synthetic STING agonists have been discovered or developed, and tested in preclinical models and in the clinic for the immunotherapy of diseases such as cancer and infectious diseases. Cyclic dinucleotides (CDNs), such as cyclic dimeric guanosine monophosphate (c-di-GMP), cyclic dimeric adenosine monophosphate (c-di-AMP), and cyclic GMP-AMP (cGAMP), are a class of STING agonists that can elicit immune responses. However, natural CDNs are hydrophilic small molecules with negative charges and are susceptible to enzymatic degradation, leading to low bioavailability in target tissues yet unwanted toxicities and narrow therapeutic windows. Drug delivery systems, coupled with nucleic acid chemistry, have been exploited to address these challenges. Here, we will discuss the underlying immunological mechanisms and approaches to STING activation, with a focus on the delivery of STING agonists, for cancer immunotherapy.
    MeSH term(s) Animals ; Humans ; Immunity, Innate/immunology ; Immunotherapy/methods ; Membrane Proteins/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Nucleic Acids/immunology ; Nucleotides, Cyclic/immunology
    Chemical Substances Membrane Proteins ; Nucleic Acids ; Nucleotides, Cyclic ; cyclic guanosine monophosphate-adenosine monophosphate
    Language English
    Publishing date 2019-10-15
    Publishing country Australia
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.37574
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  8. Article ; Online: ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response.

    Sule, Amrita / Golding, Sarah E / Ahmad, Syed F / Watson, James / Ahmed, Mostafa H / Kellogg, Glen E / Bernas, Tytus / Koebley, Sean / Reed, Jason C / Povirk, Lawrence F / Valerie, Kristoffer

    Cellular and molecular life sciences : CMLS

    2022  Volume 79, Issue 12, Page(s) 603

    Abstract: Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse ...

    Abstract Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM-PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear-cytoplasmic shuttling mediated by the nuclear export receptor CRM1.
    MeSH term(s) Animals ; Mice ; Ataxia Telangiectasia/genetics ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; Active Transport, Cell Nucleus ; DNA-Binding Proteins/metabolism ; Fibroblasts/metabolism ; Nuclear Proteins/metabolism ; DNA Damage
    Chemical Substances Protein Phosphatase 2 (EC 3.1.3.16) ; DNA-Binding Proteins ; Nuclear Proteins
    Language English
    Publishing date 2022-11-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04550-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
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  9. Article ; Online: MRE11 and ATM AKTivate pro-survival signaling.

    Golding, Sarah E / Valerie, Kristoffer

    Cell cycle (Georgetown, Tex.)

    2011  Volume 10, Issue 19, Page(s) 3227

    MeSH term(s) DNA Breaks, Double-Stranded ; DNA-Binding Proteins/metabolism ; Humans ; Proto-Oncogene Proteins c-akt/metabolism
    Chemical Substances DNA-Binding Proteins ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2011-10-01
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.10.19.17048
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5881: Show issues Location:
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  10. Article ; Online: PEAMOtecan, a novel chronotherapeutic polymeric drug for brain cancer.

    Allen, Jasmine / Wang, Juan / Zolotarskaya, Olga Yu / Sule, Amrita / Mohammad, Sajjad / Arslan, Shukaib / Wynne, Kenneth J / Yang, Hu / Valerie, Kristoffer

    Journal of controlled release : official journal of the Controlled Release Society

    2020  Volume 321, Page(s) 36–48

    Abstract: Glioblastoma multiforme (GBM) is an aggressive and difficult to treat form of brain cancer. In this work, we report on a novel chronotherapeutic polymeric drug, PEAMOtecan, for GBM therapy. PEAMOtecan was synthesized by conjugating camptothecin, a ... ...

    Abstract Glioblastoma multiforme (GBM) is an aggressive and difficult to treat form of brain cancer. In this work, we report on a novel chronotherapeutic polymeric drug, PEAMOtecan, for GBM therapy. PEAMOtecan was synthesized by conjugating camptothecin, a topoisomerase I inhibitor, to our proprietary, 'clickable' and modular polyoxetane polymer platform consisting of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (EAMO) repeat units (Patent No.: US 9,421,276) via the linker 3,3'-dithiodipropionic acid (DDPA) with a disulfide bond (SS) extended by short-chain polyethylene glycol (PEG). We show that PEAMOtecan is a highly modular polymer nanoformulation that protects covalently bound CPT until slowly being released over extended periods of time dependent on the cleavage of the disulfide and ester linkages. PEAMOtecan kills glioma cells by mitotic catastrophe with p53 mutant/knockdown cells being more sensitive than matched wild type cells potentially providing cancer-specific targeting. To establish proof-of-principle therapeutic effects, we tested PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model. PEAMOtecan was administered by one-time, convection-enhanced delivery (CED) intra-tumorally to achieve superior distribution and extended drug release over time. In addition, the near-infrared (NIR) dye Cy5.5 was coupled to the polymer providing live-animal imaging capability to track tissue distribution and clearance of the injected polymer over time. We show that PEAMOtecan significantly improves the survival of mice harboring intra-cranial tumors (p = .0074 compared to untreated group). Altogether, these results support further development and testing of our nanoconjugate platform.
    MeSH term(s) Animals ; Brain Neoplasms/drug therapy ; Cell Line, Tumor ; Drug Chronotherapy ; Drug Delivery Systems ; Glioma/drug therapy ; Mice ; Pharmaceutical Preparations ; Polymers/therapeutic use
    Chemical Substances Pharmaceutical Preparations ; Polymers
    Language English
    Publishing date 2020-02-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2020.02.003
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