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Topic Review
Lipid Metabolism and Melanoma Progression
Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. They also highlight the role of adipose tissue in tumor progression as well as the potential antitumor role of drugs targeting critical steps of lipid metabolic pathways in the context of melanoma.
  • 1.8K
  • 13 Nov 2020
Topic Review
Chitosan and Its Derivatives for Anticancer Drug Delivery
Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility.
  • 1.8K
  • 13 Jul 2023
Topic Review
Prostaglandin E2 and cancer
The involvement of inflammation in cancer progression has been the subject of research for many years. Inflammatory milieu and immune response are associated with cancer progression and recurrence. In different types of tumors, growth and metastatic phenotype characterized by the epithelial mesenchymal transition (EMT) process, stemness, and angiogenesis, are increasingly associated with intrinsic or extrinsic inflammation. Among the inflammatory mediators, prostaglandin E2 (PGE2) supports epithelial tumor aggressiveness by several mechanisms, including growth promotion, escape from apoptosis, transactivation of tyrosine kinase growth factor receptors, and induction of angiogenesis. Moreover, PGE2 is an important player in the tumor microenvironment, where it suppresses antitumor immunity and regulates tumor immune evasion, leading to increased tumoral progression.
  • 1.8K
  • 11 Dec 2020
Topic Review
Therapies for Treating HER2-Positive Advanced Breast Cancer
The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, the researchers can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, the researchers now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, the researchers have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. 
  • 1.8K
  • 22 Apr 2022
Topic Review
Cutaneous Melanoma
Cutaneous Melanoma (CM), arising from pigment-producing melanocytes in the skin, is an aggressive cancer with high metastatic potential. While cutaneous melanoma represents only a fraction of all skin cancers (<5%), it accounts for most skin-cancer-related deaths worldwide. Immune checkpoint inhibition has been the first therapeutic approach to significantly benefit patient survival after treatment. Nevertheless, the immunosuppressive tumor microenvironment and the intrinsic and acquired treatment resistance of melanoma remain crucial challenges. Combining local and systemic treatment offers the potential to augment therapeutic response and overcome resistance, although, complex drug combinations can harbor an increased risk of immune-related adverse events.
  • 1.8K
  • 22 Sep 2021
Topic Review
FGFRs in Brain Tumors
Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1–4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related to the development of the most common diseases, including cancer. FGFRs are subjected to multiple somatic aberrations such as chromosomal amplification of FGFR1; mutations and multiple dysregulations of FGFR2; and mutations, translocations, and significant amplifications of FGFR3 and FGFR4 that correlate to oncogenesis process. Therefore, the in-depth study of these receptor systems could help to understand the etiology of both astrocytoma and glioblastoma so as to achieve notable advances in more effective target therapies. Furthermore, the discovery of FGFR inhibitors revealed how these biological compounds improve the neoplastic condition by demonstrating efficacy and safety.
  • 1.8K
  • 29 Dec 2020
Topic Review
Gut Microbiome
The gut microbiome can play important role in maintaining homeostasis in the human body. An imbalance in the gut microbiome can lead to pro-inflammatory immune responses and the initiation of disease processes, including cancer. The research results prove some strains of probiotics by modulating intestinal microbiota and immune response can be used for cancer prevention or/and as adjuvant treatment during anticancer chemotherapy.
  • 1.8K
  • 15 Jan 2021
Topic Review
Neurodegeneration-Associated Protein TAU in Cancer
Neurodegenerative disorders and cancer may appear unrelated illnesses. Yet, epidemiologic studies indicate an inverse correlation between their respective incidences for specific cancers. Possibly explaining these findings, increasing evidence indicates that common molecular pathways are involved, often in opposite manner, in the pathogenesis of both disease families. Genetic mutations in the MAPT gene encoding for TAU protein cause an inherited form of frontotemporal dementia, a neurodegenerative disorder, but also increase the risk of developing cancer. Assigning TAU at the interface between cancer and neurodegenerative disorders, two major aging-linked disease families, offers a possible clue for the epidemiological observation inversely correlating these human illnesses. In addition, the expression level of TAU is recognized as a prognostic marker for cancer, as well as a modifier of cancer resistance to chemotherapy. Because of its microtubule-binding properties, TAU may interfere with the mechanism of action of taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network and impair cell division. Indeed, a low TAU expression is associated to a better response to taxanes. Although TAU main binding partners are microtubules, TAU is able to relocate to subcellular sites devoid of microtubules and is also able to bind to cancer-linked proteins, suggesting a role of TAU in modulating microtubule-independent cellular pathways associated to oncogenesis. This concept is strengthened by experimental evidence linking TAU to P53 signaling, DNA stability and protection, processes that protect against cancer.
  • 1.8K
  • 26 Nov 2020
Topic Review
Histone Monoubiquitination in Chromatin Remodelling
Chromatin remodelling is a major mechanism by which cells control fundamental processes including gene expression, the DNA damage response (DDR) and ensuring the genomic plasticity required by stem cells to enable differentiation. The post-translational modification of histone H2B resulting in addition of a single ubiquitin, in humans at lysine 120 (K120; H2Bub1) and in yeast at K123, has key roles in transcriptional elongation associated with the RNA polymerase II-associated factor 1 complex (PAF1C) and in the DDR. H2Bub1 itself has been described as having tumour suppressive roles and a number of cancer-related proteins and/or complexes are recognised as part of the H2Bub1 interactome. These include the RING finger E3 ubiquitin ligases RNF20, RNF40 and BRCA1, the guardian of the genome p53, the PAF1C member CDC73, subunits of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and histone methyltransferase complexes DOT1L and COMPASS, as well as multiple deubiquitinases including USP22 and USP44. While globally depleted in many primary human malignancies, including breast, lung and colorectal cancer, H2Bub1 is selectively enriched at the coding region of certain highly expressed genes, including at p53 target genes in response to DNA damage, functioning to exercise transcriptional control of these loci.
  • 1.8K
  • 16 Dec 2020
Topic Review
Deubiquitinating Enzyme Inhibition in Cancer
Since the discovery of the ubiquitin proteasome system (UPS), the roles of ubiquitinating and deubiquitinating enzymes (DUBs) have been widely elucidated. The ubiquitination of proteins regulates many aspects of cellular functions such as protein degradation and localization, and also modifies protein-protein interactions. DUBs cleave the attached ubiquitin moieties from substrates and thereby reverse the process of ubiquitination. The dysregulation of these two paramount pathways has been implicated in numerous diseases, including cancer. Attempts are being made to identify inhibitors of ubiquitin E3 ligases and DUBs that potentially have clinical implications in cancer, making them an important target in the pharmaceutical industry. Therefore, studies in medicine are currently focused on the pharmacological disruption of DUB activity as a rationale to specifically target cancer-causing protein aberrations. Here, we briefly discuss the pathophysiological and physiological roles of DUBs in key cancer-related pathways. We also discuss the clinical applications of promising DUB inhibitors that may contribute to the development of DUBs as key therapeutic targets in the future.
  • 1.8K
  • 09 Oct 2020
Topic Review
BCL-2 Proteins in Pathogenesis
The ability to inhibit mitochondrial apoptosis is a hallmark of B-cell non-Hodgkin lymphomas (B-NHL). Activation of mitochondrial apoptosis is tightly controlled by members of B-cell leukemia/lymphoma-2 (BCL-2) family proteins via protein-protein interactions. Altering the balance between anti-apoptotic and pro-apoptotic BCL-2 proteins leads to apoptosis evasion and extended survival of malignant cells. The pro-survival BCL-2 proteins: B-cell leukemia/lymphoma-2 (BCL-2/BCL2), myeloid cell leukemia-1 (MCL-1/MCL1) and B-cell lymphoma-extra large (BCL-XL/BCL2L1) are frequently (over)expressed in B-NHL, which plays a crucial role in lymphoma pathogenesis, disease progression, and drug resistance. 
  • 1.8K
  • 23 Jun 2021
Topic Review
Wild-type IDH Enzymes
Isocitrate dehydrogenases (IDHs) are enzymes that catalyze the oxidative decarboxylation of isocitrate, producing α-ketoglutarate (αKG) and CO2. The discovery of IDH mutations in several malignancies has led to a better characterization of IDHs involvement in tumorigenesis and the approval of drugs targeting IDH1/2 mutants in cancers. Nevertheless, less is known about the impact of IDH mutants in rare pathologies or the relevance of non-mutated IDH enzymes in cancers. Here, we provide a brief overview of the impact of IDHs enzymes as potential therapeutic targets.  
  • 1.8K
  • 30 Oct 2020
Topic Review
Natural Compounds in Glioblastoma Therapy
Glioblastoma (GBM) is a tumor of the brain or spinal cord with poor clinical prognosis. Current interventions, such as chemotherapy and surgical tumor resection, are constrained by tumor invasion and cancer drug resistance. Dietary natural substances are therefore evaluated for their potential as agents in GBM treatment. Various substances found in fruits, vegetables, and other natural products restrict tumor growth and induce GBM cell death. These preclinical effects are promising but remain constrained by natural substances’ varying pharmacological properties. While many of the reviewed substances are available as over-the-counter supplements, their anti-GBM efficacy should be corroborated by clinical trials moving forward. 
  • 1.8K
  • 23 Jun 2021
Topic Review
Gold Nanoparticles
Nanomaterials are popularly used in drug delivery, disease diagnosis and therapy. Among a number of functionalized nanomaterials such as carbon nanotubes, peptide nanostructures, liposomes and polymers, gold nanoparticles (Au NPs) make excellent drug and anticancer agent carriers in biomedical and cancer therapy application. Recent advances of synthetic technique improved the surface coating of Au NPs with accurate control of particle size, shape and surface chemistry. These make the gold nanomaterials a much easier and safer cancer agent and drug to be applied to the patient’s tumor. Although many studies on Au NPs have been published, more results are in the pipeline due to the rapid development of nanotechnology. The purpose of this review is to assess how the novel nanomaterials fabricated by Au NPs can impact biomedical applications such as drug delivery and cancer therapy. Moreover, this review explores the viability, property and cytotoxicity of various Au NPs.
  • 1.8K
  • 27 Oct 2020
Topic Review
BCR-ABL1 p210 Monitoring
The diagnostic and clinical success of standardization of BCR-ABL1 p210 monitoring in chronic myeloid leukemia patients could be seen as a good example for further standardization of molecular monitoring in other gene rearrangements. This article aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction.
  • 1.8K
  • 17 Nov 2020
Topic Review
HER2-Positive Breast Cancer
Up to one-third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mTOR pathways and metabolic adaptation. Combination therapies that simultaneously target HER2 and mTOR improve clinical outcomes compared with HER2 inhibition alone. Drugs that mimic glucose deprivation in HER2-positive breast cancer patients have not been evaluated; however, preclinical studies have shown that the growth of HER2-positive breast tumors is reduced in response to combining the glycolytic inhibitor 2-DG with mTOR inhibitors.
  • 1.8K
  • 02 Jul 2021
Topic Review
Autotaxin (ATX) in Breast Cancer
       This entry deals with the role of the secreted enzyme, autotaxin (ATX), in the progression of breast cancer. ATX produces lysophosphatidate (LPA), which signals through six G-protein coupled receptors, promoting tumor growth, metastasis, immune evasion and survival from chemotherapy and radiotherapy. Many cancer cells produce ATX, but breast cancer cells express little ATX. Instead, in breast cancer, ATX is produced by tumor-associated stroma. Breast tumors are also surrounded by adipose tissue, which is a major bodily source of ATX. In mice, a high-fat human type diet increases ATX production in adipocytes. ATX production in obesity is also increased because of low-level inflammation in the expanded adipose tissue. This increased ATX secretion and consequent LPA signaling is associated with decreased adiponectin production, which results in adverse metabolic profiles and glucose homeostasis. Increased ATX production by inflamed adipose tissue could contribute to the association between obesity and breast cancer. This would result from the cross talk between breast tumors and adjacent adipose tissue. Breast tumors produce inflammatory mediators that stimulate ATX transcription in adipocytes adjacent to the tumors. This drives a feedforward inflammatory cycle since increased LPA signaling increases the production of more inflammatory cytokines/chemokines and cyclooxygenase-2 resulting in more ATX secretion. This cycle is typical of a wound healing response, which in the case of cancers become maladaptive. Thus, inhibiting ATX activity derived from adipocytes and/or tumor stromal cells has implications as an adjuvant for breast cancer treatments by attenuating the inflammatory cycle. Targeting ATX activity and LPA signaling could potentially increase the efficacy of chemotherapy and radiotherapy independently of the breast cancer type because most ATX is not derived from breast cancer cells. Blocking ATX activity and LPA signaling could also decrease morbidity from radiation-induced fibrosis.
  • 1.8K
  • 30 Oct 2020
Topic Review
Angiogenesis
Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status.
  • 1.8K
  • 16 Jun 2021
Topic Review
Plant-Derived Nutraceuticals
The term nutraceutical combines the words nutrition and pharmaceutical and indicates those nutrient principles that are found within foods. These have beneficial health effects. Nutraceutical substances derive mainly from plants, food, and microbial sources. 
  • 1.8K
  • 12 Oct 2022
Topic Review
Glioblastoma
Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme.
  • 1.8K
  • 21 Apr 2021
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