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Cuproptosis and Tumor

Cuproptosis and Tumor PDF Author: Lin-Lin Bu
Publisher: Frontiers Media SA
ISBN: 2832540899
Category : Science
Languages : en
Pages : 188

Book Description
Cuproptosis is a new type of cell death induced by copper that differs from other types of programmed cell death. Copper ions were discovered to bind to lipoacyl proteins during the tricarboxylic acid (TCA) cycle, resulting in abnormal lipoacyl protein oligomerization. Moreover, copper ions can also reduce the level of iron-sulfur cluster proteins, thereby causing the toxic stress response in proteins and ultimately leading to cell death. So far, cuproptosis‘s role in tumors, as well as the underlying mechanisms, are still unclear and require further investigation. Recent research suggests that inducing programmed death of abnormal cells could be one of the future methods for disease treatment and prevention. It can slow the progression of the disease and, eventually, cure it by causing tumor cell cuproptosis. Currently, the drug delivery system has received a lot of attention. It is also a novel idea to treat tumors by developing a drug delivery system to induce abnormal cell cuproptosis, which will effectively reduce treatment complications and improve patients’ life quality.

Cuproptosis and Tumor

Cuproptosis and Tumor PDF Author: Lin-Lin Bu
Publisher: Frontiers Media SA
ISBN: 2832540899
Category : Science
Languages : en
Pages : 188

Book Description
Cuproptosis is a new type of cell death induced by copper that differs from other types of programmed cell death. Copper ions were discovered to bind to lipoacyl proteins during the tricarboxylic acid (TCA) cycle, resulting in abnormal lipoacyl protein oligomerization. Moreover, copper ions can also reduce the level of iron-sulfur cluster proteins, thereby causing the toxic stress response in proteins and ultimately leading to cell death. So far, cuproptosis‘s role in tumors, as well as the underlying mechanisms, are still unclear and require further investigation. Recent research suggests that inducing programmed death of abnormal cells could be one of the future methods for disease treatment and prevention. It can slow the progression of the disease and, eventually, cure it by causing tumor cell cuproptosis. Currently, the drug delivery system has received a lot of attention. It is also a novel idea to treat tumors by developing a drug delivery system to induce abnormal cell cuproptosis, which will effectively reduce treatment complications and improve patients’ life quality.

Roles of pan-cell death of tumor cells in regulating tumor immune microenvironment

Roles of pan-cell death of tumor cells in regulating tumor immune microenvironment PDF Author: Jianzhong Ai
Publisher: Frontiers Media SA
ISBN: 2832541763
Category : Medical
Languages : en
Pages : 227

Book Description


Programmed Cell Death in Cancer Progression and Therapy

Programmed Cell Death in Cancer Progression and Therapy PDF Author: Roya Khosravi-Far
Publisher: Springer Science & Business Media
ISBN: 140206554X
Category : Medical
Languages : en
Pages : 362

Book Description
Programmed cell death (PCD) plays pivotal roles in tumor progression, cancer therapeutics and resistance of tumor cells to therapy. This book examines the mechanisms involved in mediating and regulating PCD in cancer. It also provides a detailed indication of the utility of PCD in cancer therapy. The book features chapters on the current and future of RNA interference in therapeutics and Pathways involved in Stem Cell Survival and Death.

Identification of Copper Metabolism as a KRAS-specific Vulnerability in Colorectal Cancer

Identification of Copper Metabolism as a KRAS-specific Vulnerability in Colorectal Cancer PDF Author: Neethi Nandagopal
Publisher:
ISBN:
Category :
Languages : en
Pages :

Book Description
KRAS is amongst the most frequently mutated genes driving human cancers, including ~ 45% of colorectal cancers (CRC). Despite intense efforts to curb its oncogenic potential, mutant KRAS is frequently associated with drug resistance and is extremely challenging to target therapeutically. Cell-surface proteins are often spatially dysregulated in cancers and are attractive therapeutic targets due to their easy accessibility. We performed RNA sequencing of mutant KRAS-expressing intestinal epithelial cells and observed that cells undergoing transformation exhibited dramatic changes in cell surface-coding genes. Therefore, our goal was to identify novel druggable targets expressed at the cell surface of mutant KRAS-transformed cells. Using a cutting-edge cell surface proteomics approach, we identified several differentially expressed proteins at the surface of KRAS-mutant cells compared to wild-type counterparts. We then performed a cell surface based CRISPR/Cas9 screen, which revealed that loss of the copper exporter Atp7a differentially affected the fitness of intestinal epithelial cells, depending on their KRAS status. Interestingly, we found that ATP7A was upregulated in KRAS-mutant cells compared to wild-type counterparts. ATP7A has a dual role in cells; while it is essential for maturation of copper (Cu)-dependent enzymes, ATP7A protects cells from excess Cu-induced toxicity (cuproptosis). In humans, ATP7A mutations result in disorders characterized by systemic deficiencies in Cu transport and levels. In animals and in tissue culture models, including intestinal epithelial cells, intracellular Cu levels are directly correlated with the post-transcriptional abundance of ATP7A. In line with this, we observed that KRAS-mutant CRC cells and tissues had relatively more intracellular Cu, and ATP7A-overexpression protected KRAS-mutant cells from cuproptosis, compared to wild-type counterparts. We also observed that in vivo growth of KRAS-mutant xenografts was reduced when mice were fed a Cu-deficient diet. Cu is utilized by several enzymes that regulate critical cellular functions including mitochondrial respiration, cell motility and proliferation. We show that KRAS-mutant cells were more sensitive to the Cu chelating drug ammonium tetrathiomolybdate (TTM), compared to wild-type cells. Moreover, TTM-treated KRAS-mutant cells displayed reduced activities of Cu-dependent MEK1/2 and mitochondrial electron transport chain enzyme, cytochrome c oxidase (CCO). We were surprised to find that the high-affinity CTR1 importer is downregulated in KRAS-mutant cells, and so we hypothesized that KRAS cells must uptake Cu through alternate means. In accordance with this, we found that macropinocytosis acts as a non-canonical Cu-supply route in KRAS-mutant cells. In vivo, treating cells with the macropinocytosis inhibitor EIPA, inhibited the expression of ATP7A and decreased bioavailable Cu in KRAS xenografts. In conclusion, our results show that KRAS-mutant cells increase Cu and ATP7A levels, likely to support tumorigenesis by elevating cuproenzymatic activity and parallelly dealing with cuproptosis. This study is relevant to cancer as tumor tissues and patients contain higher Cu levels than normal controls. Recent studies have highlighted a potential for repurposing the clinically available copper chelator TTM, which is used to treat Cu disorders. Our results demonstrate that copper bioavailability could be exploited to treat KRAS-mutated CRC with such inhibitors. Future work includes identification of combinatorial strategies that may be synthetic lethal to copper chelation.

Application of Bioinformatics in Cancers

Application of Bioinformatics in Cancers PDF Author: Chad Brenner
Publisher: MDPI
ISBN: 3039217887
Category : Medical
Languages : en
Pages : 418

Book Description
This collection of 25 research papers comprised of 22 original articles and 3 reviews is brought together from international leaders in bioinformatics and biostatistics. The collection highlights recent computational advances that improve the ability to analyze highly complex data sets to identify factors critical to cancer biology. Novel deep learning algorithms represent an emerging and highly valuable approach for collecting, characterizing and predicting clinical outcomes data. The collection highlights several of these approaches that are likely to become the foundation of research and clinical practice in the future. In fact, many of these technologies reveal new insights about basic cancer mechanisms by integrating data sets and structures that were previously immiscible. Accordingly, the series presented here bring forward a wide range of artificial intelligence approaches and statistical methods that can be applied to imaging and genomics data sets to identify previously unrecognized features that are critical for cancer. Our hope is that these articles will serve as a foundation for future research as the field of cancer biology transitions to integrating electronic health record, imaging, genomics and other complex datasets in order to develop new strategies that improve the overall health of individual patients.

Advances in mathematical and computational oncology, volume III

Advances in mathematical and computational oncology, volume III PDF Author: George Bebis
Publisher: Frontiers Media SA
ISBN: 2832536646
Category : Medical
Languages : en
Pages : 374

Book Description


The Roles of Ion-Induced Cell Death in Cancer Treatment

The Roles of Ion-Induced Cell Death in Cancer Treatment PDF Author: Zhijie Xu
Publisher: Frontiers Media SA
ISBN: 2832519156
Category : Science
Languages : en
Pages : 315

Book Description


Functional screening for cancer drug discovery: From experimental approaches to data integration

Functional screening for cancer drug discovery: From experimental approaches to data integration PDF Author: Wenyu Wang
Publisher: Frontiers Media SA
ISBN: 2832534449
Category : Science
Languages : en
Pages : 136

Book Description


Metabolic Regulation under Oxidative Stress in Cancer

Metabolic Regulation under Oxidative Stress in Cancer PDF Author: Ali Vaziri-Gohar
Publisher: Frontiers Media SA
ISBN: 2832535690
Category : Medical
Languages : en
Pages : 165

Book Description


Precision Medicine in Gastrointestinal Cancers

Precision Medicine in Gastrointestinal Cancers PDF Author: Afsaneh Barzi
Publisher: Frontiers Media SA
ISBN: 283253290X
Category : Medical
Languages : en
Pages : 293

Book Description
Precision medicine is the main emphasis in healthcare after recognizing the importance to integrate the clinical data with the molecular data of a specific disease. The term was first introduced in 2015 in which the Precision Medicine Initiative was initiated with the final aim to provide targeted therapy with high efficacy and less toxicity. Precision medicine plays an increasingly important in gastrointestinal cancers. Gastrointestinal cancers are divided into the upper (esophagus, stomach) and lower part (hepatobiliary and colon) of the gastrointestinal system. We would like to explore the latest era of integrative therapeutic target in gastrointestinal cancers taking into consideration of various aetiologies including genetic and exposome (dietary factors, microbial, hormonal, environmental insults) and their interactions with the host microenvironment.