scholarly journals Interleukin-1β and Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1791 ◽  
Author(s):  
Cédric Rébé ◽  
François Ghiringhelli
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Gene Polymorphisms ◽  
Target Genes ◽  
Cell Types ◽  
Target Cells ◽  
Cancer Cell Proliferation ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Cellular Context

Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.

Haematotoxicology: Scientific Basis and Regulatory Aspects

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 111-113 ◽  
Author(s):  
Laura Gribaldo
Keyword(s):  
Target Genes ◽  
Cell Types ◽  
Scientific Basis ◽  
Cancer Drugs ◽  
Experimental Conditions ◽  
Clinical Drug Development ◽  
Anti Cancer ◽  
Starting Dose ◽  
Life Threatening

Haematopoietic tissues are the targets of numerous xenobiotics. The purpose of in vitro haematotoxicology is the prediction of adverse haematological effects from toxicants on human haematopoietic targets under controlled experimental conditions in the laboratory. Building on its foundations in experimental haematology and the wealth of haematotoxicological data found in experimental oncology, this field of alternatives toxicology has developed rapidly during the past decade. Preclinical and clinical drug development for anti-cancer drugs differs from that for other pharmaceuticals, because of the life-threatening nature of the disease. Treatment with anti-cancer drugs at clinically efficacious doses usually induces serious side-effects. The design of preclinical toxicology studies for anti-cancer drugs is intended to identify a safe clinical starting dose, characterise toxicities that could be encountered in human clinical trials, and determine whether these toxicities are reversible, manageable, and predictable. Although the myeloid colony-forming unit (CFU-GM) progenitor is most frequently evaluated, other defined progenitors and stem cells, as well as cell types found in the bone-marrow stroma, can now be evaluated in vitro. Genetic damage to haematopoietic cells can occur in the absence of any overt haematological signs. The development of tissue-specific screening systems that are able to give information about the toxic effects of chemicals, drugs and environmental hazards on target genes is needed, in order to make preliminary decisions or to set priorities for selection among large groups of chemicals and possible drugs.

scholarly journals Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1666
Author(s):  
Xueke Shi ◽  
Christian D. Young ◽  
Hongmei Zhou ◽  
Xiao-Jing Wang
Keyword(s):  
Growth Factor ◽  
Cancer Progression ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
The Matrix ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders

Transforming growth factor-β (TGF-β) signaling is essential in embryo development and maintaining normal homeostasis. Extensive evidence shows that TGF-β activation acts on several cell types, including epithelial cells, fibroblasts, and immune cells, to form a pro-fibrotic environment, ultimately leading to fibrotic diseases. TGF-β is stored in the matrix in a latent form; once activated, it promotes a fibroblast to myofibroblast transition and regulates extracellular matrix (ECM) formation and remodeling in fibrosis. TGF-β signaling can also promote cancer progression through its effects on the tumor microenvironment. In cancer, TGF-β contributes to the generation of cancer-associated fibroblasts (CAFs) that have different molecular and cellular properties from activated or fibrotic fibroblasts. CAFs promote tumor progression and chronic tumor fibrosis via TGF-β signaling. Fibrosis and CAF-mediated cancer progression share several common traits and are closely related. In this review, we consider how TGF-β promotes fibrosis and CAF-mediated cancer progression. We also discuss recent evidence suggesting TGF-β inhibition as a defense against fibrotic disorders or CAF-mediated cancer progression to highlight the potential implications of TGF-β-targeted therapies for fibrosis and cancer.

scholarly journals Microparticles as Biomarkers of Blood Coagulation in Cancer

2015 ◽  
Vol 7 ◽  
pp. BIC.S30347 ◽  
Author(s):  
Shosaku Nomura ◽  
Maiko Niki ◽  
Tohru Nisizawa ◽  
Takeshi Tamaki ◽  
Michiomi Shimizu
Keyword(s):  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Vascular Complications ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Breast Cancer Patients ◽  
Patient Morbidity ◽  
Increased Risk

Cancer is associated with hypercoagulopathy and increased risk of thrombosis. This negatively influences patient morbidity and mortality. Cancer is also frequently complicated by the development of venous thromboembolism (VTE). Tumor-derived tissue factor (TF)-bearing microparticles (MPs) are associated with VTE events in malignancy. MPs are small membrane vesicles released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases through expression of procoagulative phospholipids. The detection of TF-expressing MPs in cancer patients may be clinically useful. In lung and breast cancer patients, MPs induce metastasis and angiogenesis and may be indicators of vascular complications. Additionally, MPs in patients with various types of cancer possess adhesion proteins and bind target cells to promoting cancer progression or metastasis. Overexpression of TF by cancer cells is closely associated with tumor progression, and shedding of TF-expressing MPs by cancer cells correlates with the genetic status of cancer. Consequently, TF-expressing MPs represent important markers to consider in the prevention of and therapy for VTE complications in cancer patients.

scholarly journals FOXA1 defines cancer cell specificity

2016 ◽  
Vol 2 (3) ◽  
pp. e1501473 ◽  
Author(s):  
Gaihua Zhang ◽  
Yongbing Zhao ◽  
Yi Liu ◽  
Li-Pin Kao ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Target Genes ◽  
Human Cancer ◽  
Cell Types ◽  
Human Cancer Cell Lines ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Pioneer Transcription Factor ◽  
Specific Regulation

A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a “flower-blooming” hypothesis for cell-specific transcriptional regulation based on these observations.

scholarly journals Nano-Therapies for Glioblastoma Treatment

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 242 ◽  
Author(s):  
Alphandéry
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Treg Cells ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Cancer Treatments ◽  
Therapeutic Drugs ◽  
Anti Cancer ◽  
Stimulation Of ◽  
Apoptotic Mechanism

Traditional anti-cancer treatments are inefficient against glioblastoma, which remains one of the deadliest and most aggressive cancers. Nano-drugs could help to improve this situation by enabling: (i) an increase of anti-glioblastoma multiforme (GBM) activity of chemo/gene therapeutic drugs, notably by an improved diffusion of these drugs through the blood brain barrier (BBB), (ii) the sensibilization of radio-resistant GBM tumor cells to radiotherapy, (iii) the removal by surgery of infiltrating GBM tumor cells, (iv) the restoration of an apoptotic mechanism of GBM cellular death, (v) the destruction of angiogenic blood vessels, (vi) the stimulation of anti-tumor immune cells, e.g., T cells, NK cells, and the neutralization of pro-tumoral immune cells, e.g., Treg cells, (vii) the local production of heat or radical oxygen species (ROS), and (viii) the controlled release/activation of anti-GBM drugs following the application of a stimulus. This review covers these different aspects.

scholarly journals Systems-level properties of EGFR/Ras/ERK signalling amplify local signals to generate gene expression plasticity

2018 ◽  
Author(s):  
Alexander E. Davies ◽  
Taryn E. Gillies ◽  
Stefan Siebert ◽  
Michael Pargett ◽  
Savannah J. Tobin ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Cancer Cell Proliferation ◽  
Cell Plasticity ◽  
Paracrine Signalling ◽  
Heterogeneous Expression ◽  
Genetic Tumour ◽  
Proliferation And Metastasis ◽  
Erk Activity

AbstractThe EGFR/Ras/ERK signalling pathway is a driver of cancer cell proliferation and metastasis in tumours that exhibit high cell-to-cell heterogeneity. While the signalling activity of this pathway is frequently amplified in tumours, it is not understood how the kinetic aspects of its activation in tumours differ from normal cellular signalling. Using live-cell reporters of ERK signalling in the breast cancer progression series HMT-3522, we found that ERK activity in invasive cells is similar in amplitude to isogenic non-malignant cells but is highly dynamic and more disordered, leading to more heterogeneous expression of ERK target genes. Our analysis reveals that this diversification arises from systems-level functions of the pathway, including intracellular amplification of amphiregulin-mediated paracrine signalling and differential kinetic filtering by genes including Fra-1, c-Myc, and Egr1. Our findings establish a mechanism for the generation of non-genetic tumour cell plasticity arising from the specific quantitative properties of a signal transduction pathway.

scholarly journals Contrast effects of autophagy in the treatment of bladder cancer

2020 ◽  
pp. 153537022095933
Author(s):  
Ece Konac ◽  
Yener Kurman ◽  
Sümer Baltaci
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Therapy Resistance ◽  
Dual Role ◽  
Cancer Treatments ◽  
Chemotherapy Drugs ◽  
Anti Cancer

Bladder cancer is a disease that negatively affects patients’ quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy. Impact statement Autophagy acts as an intracellular recycling system. Infection and mitochondrial damage, maintaining cellular homeostasis, orchestrating nutrient stress, hypoxia, and oxidative stress are some of the physiological roles associated with autophagy. Autophagy has also context-dependent roles in cancer. Autophagy has a significant impact on tumor initiation and promotion, with both tumor-suppressive and tumor-promoting roles. Unfortunately, conventional systemic chemotherapy for cancer therapy has been reported to have primary limitations such as chemo-resistance of targeted cells. The cytoprotective role of autophagy has been postulated as one of the causes of this resistance. Hence, combination therapy using autophagy inhibitors has recently started to emerge as a noteworthy strategy in the treatment of cancer. Therefore, targeting the autophagy pathways may be a potential therapeutic strategy for addressing cancer progression or therapy resistance in the near future. This review will provide a novel insight to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion.

scholarly journals Role of the Exosome in Ovarian Cancer Progression and Its Potential as a Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1147 ◽  
Author(s):  
Koji Nakamura ◽  
Kenjiro Sawada ◽  
Masaki Kobayashi ◽  
Mayuko Miyamoto ◽  
Aasa Shimizu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Peritoneal Dissemination ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Target Cells ◽  
Distinct Form ◽  
Cargo Delivery ◽  
Different Cell Types

Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30–150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and lipids. Furthermore, therapeutic applications of exosomes as drug cargo delivery are attracting research interest because exosomes are stabilized in circulation. This review highlights the functions of exosomes in each process of the peritoneal dissemination of ovarian cancer and discusses their potential for cancer therapeutics.

scholarly journals Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4763 ◽  
Author(s):  
Atefe Abak ◽  
Alireza Abhari ◽  
Sevda Rahimzadeh
Keyword(s):  
Cancer Progression ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Donor Cell ◽  
Cell Types ◽  
Bilayer Membrane ◽  
Phospholipid Bilayer ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Phospholipid Bilayer Membrane

Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.

scholarly journals Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Serena Bonomi ◽  
Stefania Gallo ◽  
Morena Catillo ◽  
Daniela Pignataro ◽  
Giuseppe Biamonti ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cancer Progression ◽  
Cancer Treatments ◽  
Splicing Regulators ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Anti Cancer ◽  
Alternatively Spliced ◽  
Splicing Isoforms

Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer might provide a better understanding of the malignant transformation and identify novel pathways that are uniquely relevant to tumorigenesis. Understanding the molecular underpinnings of cancer-associated alternative splicing isoforms will not only help to explain many fundamental hallmarks of cancer, but will also offer unprecedented opportunities to improve the efficacy of anti-cancer treatments.

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