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Frontiers in Immunology 2022Ovarian cancer (OC) is one of the most common malignancies that causes death in women and is a heterogeneous disease with complex molecular and genetic changes. Because... (Review)
Review
Ovarian cancer (OC) is one of the most common malignancies that causes death in women and is a heterogeneous disease with complex molecular and genetic changes. Because of the relatively high recurrence rate of OC, it is crucial to understand the associated mechanisms of drug resistance and to discover potential target for rational targeted therapy. Cell death is a genetically determined process. Active and orderly cell death is prevalent during the development of living organisms and plays a critical role in regulating life homeostasis. Ferroptosis, a novel type of cell death discovered in recent years, is distinct from apoptosis and necrosis and is mainly caused by the imbalance between the production and degradation of intracellular lipid reactive oxygen species triggered by increased iron content. Necroptosis is a regulated non-cysteine protease-dependent programmed cell necrosis, morphologically exhibiting the same features as necrosis and occurring a unique mechanism of programmed cell death different from the apoptotic signaling pathway. Pyroptosis is a form of programmed cell death that is characterized by the formation of membrane pores and subsequent cell lysis as well as release of pro-inflammatory cell contents mediated by the abscisin family. Studies have shown that ferroptosis, necroptosis, and pyroptosis are involved in the development and progression of a variety of diseases, including tumors. In this review, we summarized the recent advances in ferroptosis, necroptosis, and pyroptosis in the occurrence, development, and therapeutic potential of OC.
Topics: Carcinoma, Ovarian Epithelial; Female; Ferroptosis; Humans; Necroptosis; Necrosis; Ovarian Neoplasms; Pyroptosis
PubMed: 35958626
DOI: 10.3389/fimmu.2022.920059 -
Molecular Cancer Feb 2015Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the... (Review)
Review
Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, the development of an inflammatory tumor microenvironment, and defects in programmed cell death. Programmed cell death, such as apoptosis, autophagy, and necroptosis, plays crucial roles in metastatic processes. Malignant tumor cells must overcome these various forms of cell death to metastasize. This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis, autophagy, and necroptosis involved in the regulation of cancer metastasis.
Topics: Animals; Apoptosis; Autophagy; Humans; Necrosis; Neoplasms
PubMed: 25743109
DOI: 10.1186/s12943-015-0321-5 -
Circulation Dec 2023Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common...
BACKGROUND
Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, is associated with an increased prevalence and extent of coronary artery disease. However, the mechanism through which PCOS affects cardiac health in women remains unclear.
METHODS
Prenatal anti-Müllerian hormone treatment or peripubertal letrozole infusion was used to establish mouse models of PCOS. RNA sequencing was performed to determine global transcriptomic changes in the hearts of PCOS mice. Flow cytometry and immunofluorescence staining were performed to detect myocardial macrophage accumulation in multiple PCOS models. Parabiosis models, cell-tracking experiments, and in vivo gene silencing approaches were used to explore the mechanisms underlying increased macrophage infiltration in PCOS mouse hearts. Permanent coronary ligation was performed to establish myocardial infarction (MI). Histologic analysis and small-animal imaging modalities (eg, magnetic resonance imaging and echocardiography) were performed to evaluate the effects of PCOS on injury after MI. Women with PCOS and control participants (n=200) were recruited to confirm findings observed in animal models.
RESULTS
Transcriptomic profiling and immunostaining revealed that hearts from PCOS mice were characterized by increased macrophage accumulation. Parabiosis studies revealed that monocyte-derived macrophages were significantly increased in the hearts of PCOS mice because of enhanced circulating Ly6C monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic Ly6C monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Plasma norepinephrine (a sympathetic neurotransmitter) levels and spleen size were consistently increased in women with PCOS when compared with those in control participants, and norepinephrine levels were significantly correlated with circulating CD14CD16 monocyte counts. Compared with animals without PCOS, PCOS animals showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional silencing in PCOS mice significantly suppressed cardiac inflammation and improved cardiac injury after MI.
CONCLUSIONS
Our data documented previously unrecognized mechanisms through which PCOS could affect cardiovascular health in women. PCOS may promote myocardial macrophage accumulation and post-MI cardiac remodeling because of augmented splenic myelopoiesis.
Topics: Pregnancy; Female; Humans; Mice; Animals; Polycystic Ovary Syndrome; Ventricular Remodeling; Myocardial Infarction; Heart Injuries; Inflammation; Norepinephrine
PubMed: 37937441
DOI: 10.1161/CIRCULATIONAHA.123.065827 -
British Journal of Cancer Jun 2023Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our...
BACKGROUND
Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.
METHODS
Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.
RESULTS
Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68-6.17, P < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.
CONCLUSIONS
Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.
Topics: Humans; Prognosis; Colorectal Neoplasms; Necrosis
PubMed: 37031328
DOI: 10.1038/s41416-023-02258-2 -
Journal of Cellular and Molecular... Apr 2017Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation.... (Review)
Review
Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system X inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e.g. sorafenib, artemisinin and its derivatives) can induce ferroptosis. Various factors, such as the mevalonate (MVA) and sulphur-transfer pathways, play pivotal roles in the regulation of ferroptosis. Ferroptosis plays an unneglectable role in regulating the growth and proliferation of some types of tumour cells, such as lymphocytoma, ductal cell cancer of the pancreas, renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Here, we will first introduce the discovery of and research pertaining to ferroptosis; then summarize the induction mechanisms and regulatory pathways of ferroptosis; and finally, further elucidate the roles of ferroptosis in human tumourous diseases.
Topics: Animals; Apoptosis; Humans; Iron; Metabolic Networks and Pathways; Models, Biological; Necrosis; Neoplasms
PubMed: 27860262
DOI: 10.1111/jcmm.13008 -
Oxidative Medicine and Cellular... 2021Radiation-induced brain necrosis (RBN) is a serious complication of intracranial as well as skull base tumors after radiotherapy. In the past, due to the lack of... (Review)
Review
Radiation-induced brain necrosis (RBN) is a serious complication of intracranial as well as skull base tumors after radiotherapy. In the past, due to the lack of effective treatment, radiation brain necrosis was considered to be progressive and irreversible. With better understanding in histopathology and neuroimaging, the occurrence and development of RBN have been gradually clarified, and new treatment methods are constantly emerging. In recent years, some scholars have tried to treat RBN with bevacizumab, nerve growth factor, and gangliosides and have achieved similar results. Some cases of brain necrosis can be repairable and reversible. We aimed to summarize the incidence, pathogenesis, and treatment of RBN.
Topics: Brain Neoplasms; Humans; Necrosis; Radiation Injuries
PubMed: 34976300
DOI: 10.1155/2021/4793517 -
Revista Espanola de Enfermedades... Jun 2020Pancreatic fluid collections frequently occur in the context of moderate and severe acute pancreatitis, and may also appear as a complication of chronic pancreatitis,... (Review)
Review
Pancreatic fluid collections frequently occur in the context of moderate and severe acute pancreatitis, and may also appear as a complication of chronic pancreatitis, pancreatic surgery or trauma. It is essential to adhere to the Atlanta classification nomenclature that subclassifies them into four categories (acute peripancreatic fluid collections, acute necrotic collections, pseudocysts, and walled-off necrosis) since it has an impact on prognosis and management. Pseudocysts and walled-off pancreatic necrosis are encapsulated pancreatic fluid collections characterized by a surrounding inflammatory wall, which typically develops three to four weeks after the onset of acute pancreatitis. Most pancreatic fluid collections resolve spontaneously and do not require intervention. However, when they become symptomatic or complicated drainage is indicated, and endoscopic ultrasound-guided drainage has become first-line treatment of encapsulated collections. Drainage of pseudocysts is relatively straightforward due to their liquid content. However, in walled-off necrosis the presence of solid necrotic debris can make treatment more challenging and therefore multidisciplinary management in experienced centers is recommended, being a step-up approach the current standard of care. In this review, we aim to address the management of pancreatic fluid collections with an especial focus on endoscopic drainage.
Topics: Acute Disease; Drainage; Humans; Pancreatic Pseudocyst; Pancreatitis, Acute Necrotizing
PubMed: 32450706
DOI: 10.17235/reed.2020.6814/2019 -
Cell Death & Disease Nov 2022The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent... (Review)
Review
The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.
Topics: Humans; Ferroptosis; Necrosis; Neoplasms; Iron; Immune Tolerance; Tumor Microenvironment
PubMed: 36335094
DOI: 10.1038/s41419-022-05384-6 -
Cancer Imaging : the Official... Sep 2013Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care.... (Review)
Review
Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy.
Topics: Angiogenesis Inhibitors; Cell Hypoxia; Fluorodeoxyglucose F18; Genetic Markers; Humans; Necrosis; Neoplasms; Radioisotopes
PubMed: 24061161
DOI: 10.1102/1470-7330.2013.9039 -
International Journal of Molecular... Feb 2019In the integrative theory, chronic irritations induce tumors with genetic alterations and rapid proliferative ability. Tumor cells reprogram the metabolism and employ... (Review)
Review
In the integrative theory, chronic irritations induce tumors with genetic alterations and rapid proliferative ability. Tumor cells reprogram the metabolism and employ aerobic glycolysis to sustain rapid growth. The host provides both the nutrients and exhaust system to support tumor growth via the tumor microenvironment. Under certain conditions, such as aging, diabetes, obesity and a high‑fat diet, the exhaust system is impaired, triggering a metabolic imbalance between the tumor and host. This is similar to a problematic car with an advanced motor with an out‑of‑date exhaust system. The metabolic imbalance causes a metabolic catastrophe, making tumor cells reside in a dismal environment and forcing them to invade, metastasize and undergo necrosis. Tumor necrosis, particularly in metastases, leads to non‑specific systemic inflammation, which is the major cause of cancer‑related mortality. On the whole, the integrative theory views cancer in an integrative manner and proposes that both genetic alterations and tumor‑host interaction as regards metabolism and immunology determine the destiny of the tumor and host. Although cancer is a genetic disease, tumor biology is basically the nature of the host.
Topics: Aging; Cell Communication; Diabetes Complications; Diet, High-Fat; Humans; Metabolic Networks and Pathways; Models, Theoretical; Necrosis; Neoplasm Metastasis; Neoplasms; Obesity; Tumor Microenvironment
PubMed: 30483756
DOI: 10.3892/ijmm.2018.4004