Mathematical Methods for Cancer Evolution:Lecture Notes on Mathematical Modelling in the Life Sciences. 1st ed. 2017 Takashi Suzuki
Mathematical Methods for Cancer Evolution:1st ed. 2017 Takashi Suzuki
Mechanisms of cancer prevention with curcumin and (-) epicatechin:in lung cancer cells with regard to expression of growth arrest and DNA damage inducible genes, GADD45 and GADD153 Achinto Saha, Takashi Kuzuhara
Modern Dose-Finding Designs for Cancer Phase I Trrials: Drug Combinations and Molecularly Targeted Agents:SpringerBriefs in Statistics JSS Research Series in Statistics. 1st ed. 2018 Akihiro Hirakawa, Takashi Daimon, Hiroyuki Sato, Shigeyuki Matsui
Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combinations and Molecularly Targeted Agents: Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of two agents. Development of dose-finding methods for two-agent combination trials requires reasonable models that can adequately capture joint toxicity probabilities for two agents, taking into consideration possible interactions of the two agents on toxicity probability such as synergistic or antagonistic effects. Another is clinical trials for evaluating both efficacy and toxicity outcomes in single- and two-agent combination trials. These methods are often applied to the phase I trials including MTAs because the toxicity and efficacy for a MTA does not monotonically increase with dose, but the efficacy often increases initially with the dose and then plateaus. Successful software implementations for several dose-finding methods are introduced in the book, and their operating characteristics in practice are discussed. Recent advance of the adaptive dose-finding methods in drug developments are also provided. - Akihiro Hirakawa, Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital - Takashi Daimon, Division of Biostatistics, Hyogo College of Medicine - Hiroyuki Satom, Biostatistics Group, Center for Product Evaluation, Pharmaceuticals and Medical Devices Agency - Shigeyuki Matsui, Department of Biostatistics, Nagoya University Graduate School of Medicine
Masters Thesis from the year 2016 in the subject Chemistry - Bio-chemistry, grade: 1,7, Free University of Berlin, course: Biochemie, language: English, abstract: The CRISPR-Cas system derived from bacteria and archaea adaptive immune system is a high potential method for fast genome editing that promises to revolutionize previous genome engineering. It is based on the specific targeted induced double strand break by an endonuclease. In elapsed studies PA28? figured out as an important key molecule involved in cell cycle regulation, cell signaling transcription, immune response and apoptosis. Recent investigations showed p53 to be a target of PA28? enhanced ubiquitination via MDM2 and subsequent proteasomal degradation. Otherwise mutant p53 (R248Q) has been shown as suppressor of the REG? promotor. This study aimed the CRISPR-Cas mediated gene knockout of PSME3 and tp53 in Caspase3 lacking MCF-7 breast cancer cells to investigate apoptosis. A user-developed protocol was established to implement the Multiplex CRISPR/Cas9 Assembly System Kit and the alone standing pSpCas9(BB)-2A-GFP plasmid provided by Takashi Yamamoto and Feng Zhang (Ran et al. 2013, Sakuma et al. 2014) for the generation of knockout cells. The cloning of gRNA harboring plasmids targeting PSME3 exon1/exon4 as well as tp53 exon1_1/exon1_2 was fast and in a high efficient fashion but a verification of the final constructs via T7 Endonuclease I assay was not possible. Interestingly, using fluorescent microscopy different gRNAs cloned in the CRISPR plasmids revealed variant apparent transfection efficiencies or GFP plasmid or protein stability. Furthermore, PA28? targeted cells showed a better survival than p53 knockout cells. Therefore, also no tp53 targeted cells survived the serial dilution and clonal selection over an eight week period. PSME3 exon1_F1, exon4_C8 and exon4_B9 revealed PA28? levels of about 50% compared to the untransfected wild type cells in Western Blot analyses. This could be caused by a heterozygous knockout of the PSME3 gene on chromosome17. One single cell clone (PSME3 exon4_F9) maybe carrying a gain of the PSME3 gene, undergoing interchromosomal recombination or only was hidden at one allele by the Cas9 enzyme showed 75% for PA28? levels. In summary CRISPR-Cas enabled us probable to modify the PSME3 and tp53 gene in MCF-7 cells resulting in altered survivals of the transfected cells. Additionally, first investigations of the new established MCF-7 PSME3 knockout cell lines considering the PA28? protein level showed a successful 50% reduction. It was not possible to study any apoptosis related behavior.