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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.

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.

Investigating the Evolutionary Dynamics of Drug Resistance in Colorectal Cancer

Investigating the Evolutionary Dynamics of Drug Resistance in Colorectal Cancer Book
Author : Freddie J. H. Whiting
Publisher : Unknown
Release : 2021
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Investigating the Evolutionary Dynamics of Drug Resistance in Colorectal Cancer book written by Freddie J. H. Whiting, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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.

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.

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.

Chemo resistance in Gastrointestinal Cancers

Chemo resistance in Gastrointestinal Cancers Book
Author : Xia Li,Dong-Hua Yang,Prathibha Ranganathan
Publisher : Frontiers Media SA
Release : 2022-03-30
ISBN : 288974776X
Language : En, Es, Fr & De

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Book Description :

Download Chemo resistance in Gastrointestinal Cancers book written by Xia Li,Dong-Hua Yang,Prathibha Ranganathan, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Drug Resistance in Oncology

Drug Resistance in Oncology Book
Author : S. Bernal
Publisher : CRC Press
Release : 1997-08-21
ISBN : 9781420002096
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.

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.

Colon Cancer Diagnosis and Therapy Vol 3

Colon Cancer Diagnosis and Therapy Vol  3 Book
Author : Dhananjay Shukla,Naveen Kumar Vishvakarma,Ganji Purnachandra Nagaraju
Publisher : Springer Nature
Release : 2022
ISBN : 3030727025
Language : En, Es, Fr & De

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Book Description :

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 third 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.

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.

Colon Cancer Diagnosis and Therapy

Colon Cancer Diagnosis and Therapy Book
Author : Naveen Kumar Vishvakarma,Ganji Purnachandra Nagaraju,Dhananjay Shukla
Publisher : Springer Nature
Release : 2021-06-04
ISBN : 3030646688
Language : En, Es, Fr & De

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Book Description :

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.

Colon Cancer Diagnosis and Therapy

Colon Cancer Diagnosis and Therapy Book
Author : Ganji Purnachandra Nagaraju,Dhananjay Shukla,Naveen Kumar Vishvakarma
Publisher : Springer Nature
Release : 2021
ISBN : 3030633691
Language : En, Es, Fr & De

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Book Description :

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 first 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 also 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 immunotherapeutic, nanomedicine, biomarkers, and dietary factors for the effective management of colon cancer.

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