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Topic Review
Advances in Histone Demethylase KDM3A
Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors.
  • 1.6K
  • 19 Oct 2020
Topic Review
ROS in the Tumor Microenvironment
Reactive oxygen species (ROS) are important signaling molecules in cancer. The level of ROS will determine physiological effects. While high levels of ROS can cause damage to tissues and cell death, low levels of ROS can have a proliferative effect. ROS are produced by tumor cells but also cellular components that make up the tumor microenvironment (TME).
  • 1.6K
  • 19 Aug 2021
Topic Review
Cysteine Aminotransferase
The hydrogen sulfide (H2S)-generating enzymatic system composed of cysteine aminotransferase (CAT, EC 2.6.1.3, also known as aspartate aminotransferase, AST, or glutamate transaminase, GOT), and 3-mercaptopyruvate sulfurtransferase (MST, EC 2.8.1.2), is known to be implicated in the catabolism of cysteine [1].
  • 1.6K
  • 27 Oct 2020
Topic Review
Targeting Gut Microbial Biofilms
Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
  • 1.6K
  • 22 Oct 2020
Topic Review
Mechanisms of Mitotane Action in Adrenocortical Cancer
Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. 
  • 1.6K
  • 24 Dec 2021
Topic Review
Chemotherapy Resistance
Multidrug resistance is a major factor contributing to the failure of cancer therapy and poor patient outcomes. While apoptosis (apoptotic cell death) is the desired outcome of anti-cancer therapy, chemotherapy and radiation often induce a number of mechanisms that can mediate resistance. p53 is an essential tumor suppressor and stress response protein, modulating multiple cellular responses to therapy. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to the development of drug resistance, by compromising wild type anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a conventionally cytoprotective mechanism, is often a “first responder” to chemotherapy (or radiation), by promoting the removal of damaged organelles and preventing excessive accumulation of damaged proteins; thus, autophagy, via its cytoprotectivefunction, may allow tumor cells to evade apoptotic cell death. However, substantial pre-clinical data and inconsistent clinical efficacy of autophagy inhibitors in combination with cancer chemotherapy indicates that autophagy can exhibit multiple functions and does not act solely as a cytoprotective response. Further inquiry relating to the influence of p53 status on autophagic function and its contributions to multidrug resistance will provide valuable insights towards patient response to therapy and the possibility of developing novel therapeutics for chemosensitization in the face of multidrug resistance. 
  • 1.6K
  • 16 Dec 2020
Topic Review
Superficial Spindle Cell Mesenchymal Tumors
Superficial spindle cell mesenchymal tumors form a diverse group of lesions with benign and malignant entities that are often very similar clinically and/or histologically. In children, the patient’s age; the lesion site; the presentation as a mass, nodule, or plaque; and the location in the dermis or subcutis are important features that will guide the dermatologist and the pathologist.
  • 1.6K
  • 02 Oct 2021
Topic Review
The Fra-1/AP-1 Oncoprotein
Among components of the AP-1 complex, the FOS-family transcription factor Fra-1, encoded by FOSL1, has emerged as a prominent therapeutic target. Fra-1 is overexpressed in most solid tumors, in response to the BRAF-MAPK, Wnt-beta-catenin, Hippo-YAP, IL-6-Stat3, and other major oncogenic pathways. In vitro functional analyses, validated in onco-mouse models and corroborated by prognostic correlations, show that Fra-1-containing dimers control tumor growth and disease progression. Fra-1 participates in key mechanisms of cancer cell invasion, Epithelial-to-Mesenchymal Transition, and metastatic spreading, by driving the expression of EMT-inducing transcription factors, cytokines, and microRNAs.
  • 1.6K
  • 06 May 2023
Topic Review
5-ALA Metabolic Pathway
5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 
  • 1.6K
  • 22 Jun 2022
Topic Review
Group 2 Innate Lymphoid Cells
Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors.
  • 1.6K
  • 29 Apr 2021
Topic Review
Polymeric Micelles for Anticancer Hydrophobic Drugs
Cancer has become one of the deadliest diseases in our society. Surgery accompanied by subsequent chemotherapy is the treatment most used to prolong or save the patient’s life. Still, it carries secondary risks such as infections and thrombosis and causes cytotoxic effects in healthy tissues. Using nanocarriers such as smart polymer micelles is a promising alternative to avoid or minimize these problems. These nanostructured systems will be able to encapsulate hydrophilic and hydrophobic drugs through modified copolymers with various functional groups such as carboxyls, amines, hydroxyls, etc.
  • 1.6K
  • 13 Jan 2023
Topic Review
Oncolytic Virotherapy
Some non-pathogenic viruses that do not cause serious illness in humans can efficiently target and kill cancer cells and may be considered candidates for cancer treatment with virotherapy. However, many cancer cells are protected from viruses. An important goal of personalized cancer treatment is to identify viruses that can kill a certain type of cancer cells. To this end, researchers investigate expression patterns of cell entry receptors, which viruses use to bind to and enter host cells.
  • 1.6K
  • 22 Dec 2020
Topic Review
Oral Bacteria and OSCC
Oral squamous cell carcinoma (OSCC) is an invasive epithelial neoplasm that is influenced by various risk factors, with a low survival rate and an increasing death rate. In the past few years, with the verification of the close relationship between different types of cancers and the microbiome, research has focused on the compositional changes of oral bacteria and their role in OSCC. Generally, oral bacteria can participate in OSCC development by promoting cell proliferation and angiogenesis, influencing normal apoptosis, facilitating invasion and metastasis, and assisting cancer stem cells. The study findings on the association between oral bacteria and OSCC may provide new insight into methods for early diagnosis and treatment development. 
  • 1.6K
  • 02 Nov 2020
Topic Review
Sphingolipids in Mitophagy and Cancer
Sphingolipids are membrane-associated lipids that are involved in signal transduction pathways regulating cell death, growth, and migration. In cancer cells, sphingolipids regulate pathways relevant to cancer therapy, such as invasion, metastasis, apoptosis, and lethal mitophagy. Notable sphingolipids include ceramide, a sphingolipid that induces death and lethal mitophagy, and sphingosine-1 phosphate, a sphingolipid that induces survival and chemotherapeutic resistance. These sphingolipids participate in regulating the process of mitophagy, where cells encapsulate damaged mitochondria in double-membrane vesicles (called autophagosomes) for degradation. Lethal mitophagy is an anti-tumorigenic mechanism mediated by ceramide, where cells degrade many mitochondria until the cancer cell dies in an apoptosis-independent manner.
  • 1.6K
  • 06 Jun 2021
Topic Review
L19-TNF
Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. There is  a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. 
  • 1.6K
  • 29 Mar 2022
Topic Review
Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds
More than a physical structure providing support to tissues, the extracellular matrix (ECM) is a complex and dynamic network of macromolecules that modulates the behavior of both cancer cells and associated stromal cells of the tumor microenvironment (TME). Over the last few years, several efforts have been made to develop new models that accurately mimic the interconnections within the TME and specifically the biomechanical and biomolecular complexity of the tumor ECM. Particularly in colorectal cancer, the ECM is highly remodeled and disorganized and constitutes a key component that affects cancer hallmarks, such as cell differentiation, proliferation, angiogenesis, invasion and metastasis. Therefore, several scaffolds produced from natural and/or synthetic polymers and ceramics have been used in 3D biomimetic strategies for colorectal cancer research. Nevertheless, decellularized ECM from colorectal tumors is a unique model that offers the maintenance of native ECM architecture and molecular composition.
  • 1.6K
  • 18 Jan 2022
Topic Review
Alkaloids and Their General Applications
Alkaloids are organic chemical compounds with a cyclic ring structure containing one or more basic nitrogen atoms. They are widely distributed in nature and are found as naturally occurring secondary metabolites in both plants and animals.
  • 1.6K
  • 11 Aug 2023
Topic Review
Microfluidic Device in Anti-Cancer Drug Screening
Having its root lying in microelectronics, microfluidics seems to hold great potential to explore people's limited knowledge in the field of oncology. It offers numerous advantages such as a low sample volume, minimal cost, parallelization, and portability and has been advanced in the field of molecular biology and chemical synthesis. The platform has been proved to be valuable in cancer research, especially for diagnostics and prognosis purposes and has been successfully employed in recent years. Organ-on-a-chip, a biomimetic microfluidic platform, simulating the complexity of a human organ, has emerged as a breakthrough in cancer research as it provides a dynamic platform to simulate tumor growth and progression in a chip.
  • 1.6K
  • 15 Jul 2022
Topic Review
Neutrophil
Neutrophils represent about 50–70% of all white blood cells in the human circulation and are widely recognized as the first line of defense in infectious disease. However, neutrophils also have a clear modulatory role in human diseases such as cancer, respiratory disease, and autoimmunity. Infections and/or any inflammatory signals trigger a rapid influx of neutrophils from the peripheral blood to the inflammatory site, where they can utilize a broad variety of effector functions to.  Neutrophils are well known phagocytic cells, engulfing microorganisms or in case of bigger targets, such as cancer cells, taking “bites” of the membrane in a process called ‘trogocytosis’. Moreover, neutrophils are armed with granules that are loaded with proteases and inflammatory mediators  that are released upon activation. In addition, during a so called ‘oxidative burst’ neutrophils release high levels of  reactive oxygen species (ROS), which can trigger cell death of the target cell. Finally, neutrophils can entrap foreign materials in so called ‘neutrophil extracellular traps’ (NETs), which are mainly composed of neutrophil DNA and Granular contents. The effector functions of neutrophils can be triggered by antibodies that activate  neutrophils by binding to Fc-receptors (FcRs), leading to antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Although neutrophils are mainly involved in innate immunity, neutrophils contribute to adaptive immune responses. 
  • 1.6K
  • 05 Jan 2021
Topic Review
Vitamin D arrests cell cycling
Vitamin D is a steroid hormone crucial for bone mineral metabolism. In addition, vitamin D has pleiotropic actions in the body, including anti-cancer actions. These anti-cancer properties observed within in vitro studies frequently report the reduction of cell proliferation by direct alteration of cell cycle regulators which induce cell cycle arrest. The most recurrent reported mode of cell cycle arrest by vitamin D is at the G1/G0 phase of the cell cycle. This arrest is mediated by p21 and p27 upregulation, which results in suppression of cyclin D and E activity which leads to G1/G0 arrest. In addition, vitamin D treatments within in vitro cell lines have observed a reduced C-MYC expression and increased retinoblastoma protein levels that also result in G1/G0 arrest.
  • 1.6K
  • 16 Dec 2020
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