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Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies

Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies
A Book

by Chi Hin Cho,Tao Hu

  • Publisher : Academic Press
  • Release : 2020-06-22
  • Pages : 240
  • ISBN : 0128199377
  • Language : En, Es, Fr & De
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Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer. Presents a systemic summary of molecular mechanisms for a quick and in-depth understanding Updates current trends in the field with pioneering information on drug resistance Encompasses both basic and clinical approaches for a better understanding of unsolved problems from a holistic point-of-view

Investigation of Mechanisms of Drug Resistance in Colorectal Cancer

Investigation of Mechanisms of Drug Resistance in Colorectal Cancer
A Proteomic and Pharmacological Study Using Newly Developed Drug-resistant Human Cell Line Subclones

by M. Ortega Duran

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Identification of Novel MiRNAs Contributing to Drug Resistance in Colorectal Cancer

Identification of Novel MiRNAs Contributing to Drug Resistance in Colorectal Cancer
A Book

by Yang Zang

  • Publisher : Unknown Publisher
  • Release : 2015
  • Pages : 346
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Colorectal cancer is the third most common diagnosed and the second leading lethal cancer in the United States. Development of drug resistance is one of the primary causes of colorectal cancer relapse yet underlying mechanisms is still largely unknown and therapeutic treatments remain limited. Here we show that expression of miR-520g/miR-587 is correlated with drug resistance of colon cancer cells. Ectopic expression of miR-520g/miR-587 confers resistance to 5-FU or oxaliplatin-induced apoptosis in vitro and attenuates the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-520g mediates drug resistance through down-regulation of p21 expression. Moreover, p53 suppresses miR-520g expression. Inhibition of miR-520g in p53 -/- cells increases their sensitivity to 5-FU treatment. On the other hand, MiR-587 modulates drug resistance through down-regulation of expression of PPP2R1B, which is a direct target of miR-587. Knockdown of PPP2R1B up-regulates pAKT (T308) and XIAP expression, enhancing resistance to 5-FU in colorectal cancer cells, whereas rescue of PPP2R1B in MiR-587 expressing cells decreases pAKT(308) and XIAP expression and re-sensitizes the cells to 5-FU treatment. An AKT inhibitor MK2206 significantly reduces pAKT(T308) and XIAP expression in MiR-587 expressing cells, neutralizing the resistance of the cells to 5-FU cytotoxicity. In addition, inhibition of miR-587 in colon cancer cells increases their sensitivity to 5-FU treatment through the PPP2R1B/pAKT/XIAP signaling axis. Importantly, studies of patient samples indicate that expression of miR-520g/miR-587 correlates with chemoresistance in colorectal cancer, while expression of PPP2R1B is reversely correlated with chemoresistance in these patient samples. these findings indicate that the p53/miR-520g/p21 and miR-587/PPP2R1B/pAKT/XIAP signaling axis play important roles in mediating response to chemotherapy in colorectal cancer. A major implication of our studies is that inhibition of miR-520g/miR-587 or restoration of p21/PPP2R1B expression may have therpeutic potential to overcome drug resistance in colorectal cancer patients.

Notch Signaling Mediates Drug Resistance in Colorectal Cancer Cells Via Effects on DNA Repair Proteins

Notch Signaling Mediates Drug Resistance in Colorectal Cancer Cells Via Effects on DNA Repair Proteins
A Book

by Dennis George

  • Publisher : Unknown Publisher
  • Release : 2016
  • Pages : 79
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States and the third most commonly diagnosed cancer in men and women. Despite tremendous progress in diagnosis, prevention, and treatment efforts, tumor recurrence and chemoresistance remain as considerable challenges. Treatment options are limited if surgery and chemotherapy are unsuccessful. Several studies have implicated the Notch signaling pathway in conferring drug resistance to tumor cells, in addition to increased CRC aggressiveness and potential for metastatic spread. Our group previously showed that Notch-1 signaling is highly associated with promoting cancer stem cell properties in CRC cells. Furthermore, we have also confirmed that human colon tissue samples isolated from CRC patients indicate higher expression of DNA repair proteins associated with Base Excision Repair (BER). Herein, we hypothesized that Notch signaling confers drug resistance to tumor cells via signaling effects on critical proteins associated with DNA repair. Methods: The experiments conducted in this study utilized the colon cancer cell line HCT-116. These cells were transduced with an IRES-GFP retrovirus expressing human intracytoplasmic domain of Notch-1 (ICN1). Another group of HCT-116 cells was transduced with a small hairpin mRNA construct (sh59) that effectively knocked out Notch-1 action. Cell lines were exposed to varying concentrations of cytarabine and cisplatin, potent DNA damaging agents, and observed for chemosensitivity. Western blot analysis was performed using standard methodology. Results: Small hairpin mRNA (sh59) transduction into the colon tumor cell line HCT-116 resulted in a significantly decreased expression of critical BER DNA repair enzymes, Poly (ADP-Ribose) Polymerase 1 (PARP1) and 8-Oxoguanine glycosylase (OGG1). These changes were accompanied by significantly higher chemosensitivity of these cells to cytarabine and cisplatin treatment as opposed to cells expressing constitutively active Notch-1 signaling. Furthermore, cells with intact Notch signaling expressed upto two-fold increase in expression of APE1 following treatment with cytarabine compared to cells with no Notch-1 expression. Conclusions: These data indicate a key role for Notch signaling in conferring drug resistance to CRC cells via effects on critical proteins of DNA repair. This finding highlights the potential use of Notch-1 inhibitors in combination with PARP1 inhibitors to effectively target highly drug resistant CRC cells.

Characterising Changes in Adhesion and Enzyme Activity Related to Drug Resistance in Colon Cancer Cells

Characterising Changes in Adhesion and Enzyme Activity Related to Drug Resistance in Colon Cancer Cells
A Book

by Heather Dekker

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 78
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Metastatic colorectal cancer is often fatal, and drug resistance to chemotherapeutic agents is one of the primary contributing factors to this lethality. Drug resistance arises from exposure to chemotherapies, and it can be mediated through a variety of mechanisms. One of these mechanisms is alteration of enzymes within the cancer cells to affect the processing or removal of the drug. Carboxylesterase is an example of an enzyme that converts irinotecan, a drug used in metastatic colorectal cancer treatments, into the active metabolite SN-38. Carboxylesterase enzymes are found in high quantities in both the liver and intestinal cells. The presence of carboxylesterase in intestinal and liver cells is an important consideration in the processing of colorectal cancer treatments. Glutathione S-transferase is another enzyme that has been implicated in drug resistance because of its ability to conjugate reduced glutathione to xenobiotic substances, facilitating their removal. Additionally, drug resistance can affect the behaviours of cells. Drug-resistant cells can exhibit changes in their motility and aggressiveness compared to drug-sensitive cells. In this study I investigated cellular behavioural changes in SN-38-resistant colon cancer cells compared to their SN-38-sensitive counterparts. In addition to behavioural changes, I also sought to determine if elevations in carboxylesterase and glutathione S-transferase enzymes were contributing to the drug resistance in these colon cancer cells.

Combination Therapy as a Promising Strategy to Overcome Drug Resistance in Colorectal Cancer

Combination Therapy as a Promising Strategy to Overcome Drug Resistance in Colorectal Cancer
A Book

by Benardina Ndreshkjana

  • Publisher : Unknown Publisher
  • Release : 2019
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Mathematical Modeling of Drug Resistance Due to KRAS Mutation in Colorectal Cancer

Mathematical Modeling of Drug Resistance Due to KRAS Mutation in Colorectal Cancer
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2016
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Delivery of Fluorouracil and SiRNA by Mesoporous Silica Nanoparticles to Drug Resistant Colorectal Cancer

Delivery of Fluorouracil and SiRNA by Mesoporous Silica Nanoparticles to Drug Resistant Colorectal Cancer
A Book

by Lijue Chen

  • Publisher : Unknown Publisher
  • Release : 2015
  • Pages : 183
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Mesoporous silica nanoparticle based drug and gene delivery system was developed to overcome the acquired drug resistance in colorectal cancer by targeted delivery of anti-cancer drug in the cytoplasm of the cancer cells and silencing the gene expression related to drug resistance.

Polymorphism and Expression of Drug Resistance Genes in Colorectal Cancer Patients Given Adjuvant Folfox-4 Chemotheraphy

Polymorphism and Expression of Drug Resistance Genes in Colorectal Cancer Patients Given Adjuvant Folfox-4 Chemotheraphy
A Book

by Mojgan Mirakhrli

  • Publisher : Unknown Publisher
  • Release : 2011
  • Pages : 480
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Non-Canonical Pathways Induced Drug Resistance in Musashi-1 Positive Colorectal Cancer Stem Cell Lineages

Non-Canonical Pathways Induced Drug Resistance in Musashi-1 Positive Colorectal Cancer Stem Cell Lineages
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy

Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy
Targeted Therapies to Reverse Resistance

by Benjamin Bonavida

  • Publisher : Springer Science & Business Media
  • Release : 2013-07-04
  • Pages : 260
  • ISBN : 1461470706
  • Language : En, Es, Fr & De
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​​​​​This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.

The Roles of MLH1 and MSH2 in Growth and Drug Resistance in Human Colorectal Cancer Cells

The Roles of MLH1 and MSH2 in Growth and Drug Resistance in Human Colorectal Cancer Cells
A Book

by Amanda Barber

  • Publisher : Unknown Publisher
  • Release : 2012
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The Role of E-cadherin in Colon Cancer Drug Resistance

The Role of E-cadherin in Colon Cancer Drug Resistance
A Book

by Lynn Murray

  • Publisher : Unknown Publisher
  • Release : 2010
  • Pages : 226
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Musashi-1 as a Switch of CD44/CD44v6-positive Cancer Stem Cell Lineage Transformations and Acquired Drug Resistance in Colorectal Cancer Cell

Musashi-1 as a Switch of CD44/CD44v6-positive Cancer Stem Cell Lineage Transformations and Acquired Drug Resistance in Colorectal Cancer Cell
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2015
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Drug Resistance in Oncology

Drug Resistance in Oncology
A Book

by S. Bernal

  • Publisher : CRC Press
  • Release : 1997-08-21
  • Pages : 416
  • ISBN : 9781420002096
  • Language : En, Es, Fr & De
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This timely new reference integrates the latest clinical results and laboratory studies on the resistance of specific cancers to chemotherapeutic drugs-covering drug resistance in lung, breast, ovary, and colon cancer as well as hematological malignancies.

ITRAQ-based Quantitative Proteomic Analysis of Mammalian Cell Lines

ITRAQ-based Quantitative Proteomic Analysis of Mammalian Cell Lines
A Book

by Vida Talebian

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 100
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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High-throughput proteomics approaches have been successfully employed in the inclusive and unbiased characterization of cellular proteome. In this thesis, we are aiming to comprehensively compare changes in proteome expression in mammalian cell lines under two different conditions. The first is an analysis of mAb producing CHO cells with a focus on comparing the productivity of inducible cells, and the second investigates human colorectal cancer cells with a focus on chemo-resistant cells. To this end, the quantitative proteomics technique iTRAQ was performed on the samples. The production of monoclonal antibodies as therapeutic medicines has gained increasing attention and applications in the last decades. Improving production levels is an important issue that can economically impact the industry. Chinese hamster ovary (CHO) cells are the most commonly used mammalian cell lines for the production of therapeutic mAbs and have been genetically modified for this purpose. Monitoring the effects of genetic modification systems on the cells is very important to maintain the quality and consistency of the cellular products. The possible changes or stresses forced on the cells after these modifications can be observed by analyzing the cells' proteome and can enable the development of optimized expression systems. Also, the biological characteristics of high-producing CHO cells could be obtained by proteomic comparison of these cells. We quantified the expression levels of 1,616 unique proteins from an iTRAQ MS analysis and identified 81 proteins with p-values lower than 0.05 where the highest fold-change belong to the mAb sequence. Overall, proteins did not show any large changes based on the fold-change and it is likely that the induction system with cumate gene switch did not cause large metabolic changes or stress responses in the CHO cells. With these results we can suggest that the system has generated a stable cell line with a higher capacity for mAb production without inducing any major stress responses in the cells, and the cell line could have the potential for high mAb production using a stronger promoter system. The second topic of interest in this thesis is therapy resistance colorectal cancer, which is either caused by a selection or induction of drug resistance in a subset of colorectal cancer cells. Drug resistance is the first reason for treatment failure or metastasis, therefore understanding the biological features of resistant cells can be helpful. To this end, the cancer cell line, HT-29, and a SN-38 drug-resistant HT-29 cell line were explored by iTRAQ quantitative proteomic analysis. SN-38 is the active metabolite of the chemotherapy drug, irinotecan, a common mediation for treating colon cancer. The expression levels of 1,665 proteins were quantified and 21 proteins had significant changes with more than 1 log-fold-change. PAGE4 is the most up-regulated protein in the resistant HT-29 cells; it shows to have a role in cell viability and survival. Among the down-regulated proteins, cytokeratin (KRT20) had a significant low expression in resistant HT-29 cells that can show the change in cell migration because it is known for circulating CRC cells. Biosynthesis of antibiotics is identified as the most enriched KEGG pathway within the up-regulated genes; also, ribosome pathway is observed as the most enriched pathway among the down-regulated gene list. Overall, a large number of the differentially regulated genes were known in the stem cancer cells, EMT processes and metastasis. The main functions among the differentially regulated proteins is related to cell adhesion and migration, cell proliferation, and the ribosome.

Colon Cancer Diagnosis and Therapy

Colon Cancer Diagnosis and Therapy
Volume 2

by Naveen Kumar Vishvakarma

  • Publisher : Springer Nature
  • Release : 2021
  • Pages : 459
  • ISBN : 3030646688
  • Language : En, Es, Fr & De
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Colorectal cancer (CRC) is a major global health challenge as the third leading cause for cancer related mortalities worldwide. Despite advances in therapeutic strategies, the five-year survival rate for CRC patients has remained the same over time due to the fact that patients are often diagnosed in advanced metastatic stages. Drug resistance is another common reason for poor prognosis. Researchers are now developing advanced therapeutic strategies such as immunotherapy, targeted therapy, and combination nanotechnology for drug delivery. In addition, the identification of new biomarkers will potentiate early stage diagnosis. This book is the second of three volumes on recent developments in colorectal diagnosis and therapy. Each volume can be read on its own, or together. Each volume focuses on different novel therapeutic advances, biomarkers, and identifies therapeutic targets for treatment. Written by leading international experts in the field, coverage addresses the role of diet habits and lifestyle in reducing gastrointestinal disorders and incidence of CRC. Chapters discuss current and future diagnostic and therapeutic options for colorectal cancer patients, focusing on immunotherapeutics, nanomedicine, biomarkers, and dietary factors for the effective management of colon cancer.

Mechanisms of Drug Resistance in Neoplastic Cells

Mechanisms of Drug Resistance in Neoplastic Cells
Bristol-Myers Cancer Symposia

by Paul V. Woolley,Kenneth D. Tew

  • Publisher : Elsevier
  • Release : 2017-01-31
  • Pages : 416
  • ISBN : 1483220753
  • Language : En, Es, Fr & De
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Bristol-Myers Cancer Symposia, Volume 9: Mechanisms of Drug Resistance in Neoplastic Cells provides information on both basic scientific and clinical studies on the causes and implications of tumor cell resistance to common antineoplastic agents. The book describes the colon cancer as a model for resistance to antineoplastic drugs; mathematical modeling of drug resistance; and the mechanism of induced gene amplification in mammalian cells. The text also discusses the cellular concomitants of multidrug resistance; resistance to alkylating agents; and the phosphoprotein and protein kinase C changes in human multidrug-resistant cancer cells. Novel drugs that affect glutathione metabolism; the regulation of genes encoding drug-metabolizing enzymes in normal and preneoplastic tissues; and the relevance of glutathione S-transferases to anticancer drug resistance are also considered. The book further tackles the cellular resistance to cyclophosphamide; the preclinical and clinical experiences with drug combinations designed to inhibit DNA repair in resistant human tumor cells; and the modification of the cytotoxicity of DNA-directed chemotherapeutic agents by polyamine depletion. The text also demonstrates multidrug resistance and the circumvention of resistance. Oncologists, molecular biologists, biochemists, geneticists, and pharmacologists will find the book invaluable.

Characterization of Human Colorectal Cancer Stem Cells and Their Role in Chemoresistance

Characterization of Human Colorectal Cancer Stem Cells and Their Role in Chemoresistance
A Book

by Stacey J. Butler

  • Publisher : Unknown Publisher
  • Release : 2015
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Sensitization of Cancer Cells for Chemo/Immuno/Radio-therapy

Sensitization of Cancer Cells for Chemo/Immuno/Radio-therapy
A Book

by Benjamin Bonavida

  • Publisher : Springer Science & Business Media
  • Release : 2008-07-31
  • Pages : 420
  • ISBN : 9781597454742
  • Language : En, Es, Fr & De
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This book reviews novel approaches developed to reverse tumor cell resistance to chemo/immuno/radio-therapy and the use of various sensitizing agents in combination with various cytotoxics. It also introduces several current approaches developed by established investigators that are aimed at overcoming resistance. This is the first volume to compile studies on tumor cell sensitization. It will prove useful for students, scientists, clinicians and pharmaceutical companies.