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Drug Resistance In Colorectal Cancer

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Drug Resistance in Colorectal Cancer Molecular Mechanisms and Therapeutic Strategies

Drug Resistance in Colorectal Cancer  Molecular Mechanisms and Therapeutic Strategies Book
Author : Chi Hin Cho,Tao Hu
Publisher : Academic Press
Release : 2020-05-24
ISBN : 0128199385
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : M. Ortega Duran
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Investigation of Mechanisms of Drug Resistance in Colorectal Cancer book written by M. Ortega Duran, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Identification of Novel MiRNAs Contributing to Drug Resistance in Colorectal Cancer

Identification of Novel MiRNAs Contributing to Drug Resistance in Colorectal Cancer Book
Author : Yang Zang
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Dennis George
Publisher : Unknown
Release : 2016
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Heather Dekker
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

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 Book
Author : Lijue Chen
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy

Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy Book
Author : Benjamin Bonavida
Publisher : Springer Science & Business Media
Release : 2013-07-04
ISBN : 1461470706
Language : En, Es, Fr & De

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Book Description :

​​​​​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.

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 Book
Author : Mojgan Mirakhrli
Publisher : Unknown
Release : 2011
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Polymorphism and Expression of Drug Resistance Genes in Colorectal Cancer Patients Given Adjuvant Folfox 4 Chemotheraphy book written by Mojgan Mirakhrli, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

The Role of E cadherin in Colon Cancer Drug Resistance

The Role of E cadherin in Colon Cancer Drug Resistance Book
Author : Lynn Murray
Publisher : Unknown
Release : 2010
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download The Role of E cadherin in Colon Cancer Drug Resistance book written by Lynn Murray, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Mechanisms of Drug Resistance in Neoplastic Cells

Mechanisms of Drug Resistance in Neoplastic Cells Book
Author : Paul V. Woolley,Kenneth D. Tew
Publisher : Elsevier
Release : 2017-01-31
ISBN : 1483220753
Language : En, Es, Fr & De

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Book Description :

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.

Drug Resistance in Oncology

Drug Resistance in Oncology Book
Author : S. Bernal
Publisher : CRC Press
Release : 1997-08-21
ISBN : 9780824792954
Language : En, Es, Fr & De

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Book Description :

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.

Notch 3 Affects Chemoresistance in Colorectal Cancer Via DNA Base Excision Repair Enzymes

Notch 3 Affects Chemoresistance in Colorectal Cancer Via DNA Base Excision Repair Enzymes Book
Author : Azeem Khan
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Approximately 1.2 million cases of colorectal cancer (CRC) arise each year, and 40-50% of CRC patients will reach metastasis. The Notch pathway is known to be dysregulated in CRC, and its relationship with DNA repair mechanisms, which contribute to drug resistance, is currently being established. Previously, we observed a decrease in DNA base excision repair (BER) enzymes and drug resistance upon Notch 1 targeting. We have also observed that Notch 1 signaling is associated with promoting cancer stemness and epithelial to mesenchymal transition in CRC via upregulation of the Notch 3 receptor. Thus, we hypothesized that targeting Notch 3 will increase drug sensitivity in CRC via signaling effects on proteins associated with the DNA BER mechanism. Methods: In order to assess our hypothesis, the colon cancer cell line HCT 116 was transduced with a small hairpin messenger RNA construct that effectively knocked down the Notch 3 receptor, creating the Sh-N3 cell line. Culturing and Western blot analyses were conducted using standard methodology. Drug resistance was analyzed by treating cells with cisplatin or cytarabine, potent DNA damaging agents, and cytotoxicity was assessed. Microscopy was used to confirm effects of the DNA damaging agents. Proteins from the Notch 3 receptor targeted cell line treated with the DNA damaging agents were also studied. Results: Notch 3 targeted (Sh-N3) cells resulted in 1.5-fold lower plating efficiency compared to their counterpart controls (p

Drug Resistance Mechanisms to Gamma secretase Inhibitors in Human Colon Cancer Cells

Drug Resistance Mechanisms to Gamma secretase Inhibitors in Human Colon Cancer Cells Book
Author : Cindy R. Timme
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

We show that GSIs may block apoptosis and induce cytoprotective autophagy simultaneously, resulting in increased drug resistance and cellular survival. Whether these two cellular survival processes occurs in patients needs to be examined before GSIs can be utilized in a clinical setting. If so, these two hurdles must be overcome.

Anticancer Research

Anticancer Research Book
Author : Anonim
Publisher : Unknown
Release : 2008
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Anticancer Research book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Colorectal Cancer

Colorectal Cancer Book
Author : Jindong Chen
Publisher : BoD – Books on Demand
Release : 2018-05-16
ISBN : 1789231000
Language : En, Es, Fr & De

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Book Description :

With international experts sharing their experience and knowledge on these different aspects in the management of colorectal cancer, this book has this opportunity to offer all physicians treating colorectal cancer, as well as researchers, updated information concerning the biology, diagnosis, screening, and treatment of colorectal carcinoma. This book provides a detailed evaluation of diagnostic modalities, in-depth analysis of screening for colorectal cancer, recent advances in treatment, and principles and trends in the management of colorectal cancer. This updated knowledge will be an interesting and informative read for any clinician involved in the management of patients with colorectal cancer. In addition, readers such as related physicians, researchers, and colorectal cancer patients are potential beneficiaries of this book.