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Topic Review
Breast Cancer and Bone Mineral Density
Breast cancer is associated with phosphate toxicity, the toxic effect from dysregulated phosphate metabolism that can stimulate tumorigenesis. Phosphate toxicity and dysregulated phosphate metabolism are also associated with bone mineral abnormalities, including excessive bone mineral loss and deposition.
  • 477
  • 26 Oct 2023
Topic Review
Therapies Targeting Bruton Tyrosine Kinase for CLL
The development of inhibitors of Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) has resulted in a paradigm shift in the treatment of chronic lymphocytic leukaemia (CLL). Observations regarding the importance of B-cell receptor signalling for the survival and proliferation of CLL cells led to the development of the first-in-class BTK inhibitor (BTKi), ibrutinib, for the treatment of CLL. Despite being better tolerated than chemoimmunotherapy, ibrutinib does have side effects, some of which are due to the off-target inhibition of kinases other than BTK. As a result, more specific inhibitors of BTK were developed, such as acalabrutinib and zanubrutinib, which have demonstrated equivalent/enhanced efficacy and improved tolerability in large randomized clinical trials. Despite the increased specificity for BTK, side effects and treatment resistance remain therapeutic challenges. As these drugs all bind covalently to BTK, an alternative approach was to develop noncovalent inhibitors of BTK, including pirtobrutinib and nemtabrutinib. The alternative mechanisms of BTK-binding of these agents has the potential to overcome resistance mutations, something that has been borne out in early clinical trial data.
  • 476
  • 19 May 2023
Topic Review
Unraveling the Wide Spectrum of Melanoma Biomarkers
The use of biomarkers in medicine has become essential in clinical practice in order to help with diagnosis, prognostication and prediction of treatment response. Since Alexander Breslow’s original report on “melanoma and prognostic values of thickness”, providing the first biomarker for melanoma, many promising new biomarkers have followed. These include serum markers, such as lactate dehydrogenase and S100 calcium-binding protein B. However, as our understanding of the DNA mutational profile progresses, new gene targets and proteins have been identified. These include point mutations, such as mutations of the BRAF gene and tumour suppressor gene tP53. At present, only a small number of the available biomarkers are being utilised, but this may soon change as more studies are published. The aim of this article is to provide a comprehensive review of melanoma biomarkers and their utility for current and, potentially, future clinical practice.
  • 475
  • 20 Sep 2023
Topic Review
Role of Midkine in Hepatocellular Carcinoma
Midkine (MDK) is a multifunctional secreted protein that can act as a cytokine or growth factor regulating multiple signaling pathways and being implicated in fundamental cellular processes, such as survival, proliferation, and migration. Although its expression in normal adult tissues is barely detectable, MDK serum levels are found to be elevated in several types of cancer, including hepatocellular carcinoma (HCC). 
  • 475
  • 25 Jan 2024
Topic Review
Fluorescence Molecular Targeting of Colon Cancer
Colorectal cancer (CRC) is a common cause of cancer and cancer-related death. Surgery is the only curative modality. Fluorescence-enhanced visualization of CRC with targeted fluorescent probes that can delineate boundaries and target tumor-specific biomarkers can increase rates of curative resection. Approaches to enhancing visualization of the tumor-to-normal tissue interface are active areas of investigation.
  • 474
  • 26 Apr 2022
Topic Review
Non-Invasive Imaging Modalities for Bladder Cancer in Mice
Bladder cancer (BCa) requires the investigation of alternative therapies. Prior to clinical testing, researchers require the use of animal models to thoroughly investigate their therapeutic efficacy. To appropriately mimic cancer response, the cancer must be developed and treated within the relevant organ. This creates an obstacle with BCa, as cancer presence and progression are difficult to evaluate due to its location. Therefore, non-invasive techniques have been developed that allow for visualization of the cancer from outside the bladder.
  • 473
  • 04 May 2023
Topic Review
From Circulating Tumor Cells to Mirna
Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity.
  • 473
  • 24 Aug 2023
Topic Review
Molecular Mechanisms for Resistance to Poly(ADP-ribose) Polymerase Inhibition
Inhibitors of PARP have been designed so that that they can be useful in the clinic by using their synthetic lethality feature. PARP inhibitors are known as the first synthetic-lethality-inducing agents allowed to be used in the clinic. Although PARP1 inhibitors are primarily used in the clinic to treat cancers with an impaired homologous recombination signaling pathway (especially BRCA1 mutation), they have recently been used as part of an adjunctive therapy in other solid cancers. This was based on the possibility that carriers without a HRD are susceptible to PARPi due to their BRCAness dependency.
  • 472
  • 02 Jan 2024
Topic Review
Circulating Cell-Free DNA in Renal Cell Carcinoma
Tumor biopsy is still the gold standard for diagnosing and prognosis renal cell carcinoma (RCC). However, its invasiveness, costs, and inability to accurately picture tumor heterogeneity represent major limitations to this procedure. Analysis of circulating cell-free DNA (cfDNA) is a non-invasive cost-effective technique that has the potential to ease cancer detection and prognosis. In particular, cfDNA could be a complementary tool to identify and prognosticate RCC while providing contemporary mutational profiling of the tumor.
  • 470
  • 08 Oct 2022
Topic Review
Androgen Receptor’s Role in Triple Negative Breast CancerBC
Triple negative breast cancer (TNBC) comprises 10–20% of diagnosed breast cancers. TNBCs are devoid of common biomarkers such as an estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Research is being conducted to determine the androgen receptor’s (AR) role in TNBC and determine its ability to be utilized as an effective drug target in the absence of the commonly targeted receptors. 
  • 468
  • 22 Jan 2024
Topic Review
Hallmarks of the Tumour Microenvironment of Gliomas
Gliomas are aggressive, primary central nervous system tumours arising from glial cells. Glioblastomas are the most malignant. They are known for their poor prognosis or median overall survival. The advent of immunotherapy with its various modalities—immune checkpoint inhibitors, cancer vaccines, oncolytic viruses and chimeric antigen receptor T cells and NK cells—has shown promise. 
  • 467
  • 14 Sep 2023
Topic Review
Signaling Lymphocyte Activation Molecule Receptors in Oncology
In the field of oncology, the Signaling Lymphocyte Activation Molecule (SLAM) family is emerging as pivotal in modulating immune responses within tumor environments. The SLAM family comprises nine receptors, mainly found on immune cell surfaces. These receptors play complex roles in the interaction between cancer and the host immune system. Research suggests SLAM’s role in both enhancing and dampening tumor-immune responses, influencing the progression and treatment outcomes of various cancers.
  • 467
  • 12 Oct 2023
Topic Review
Clinical Management of pT1 Colorectal Cancer
Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis.
  • 466
  • 26 Sep 2023
Topic Review
Radiosurgery for Brain Metastases
Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving local tumor control, reducing toxicity, and minimizing the need for whole-brain radiation therapy (WBRT). Nevertheless, radiation treatment may induce brain changes, visible in neuroimaging, that are often difficult to distinguish from progressive disease.
  • 465
  • 31 Oct 2023
Topic Review
Therapeutic Potential of Vaccinium Berries in Breast Cancer
Breast cancer (BC) is the largest contributor to cancer deaths in women worldwide. Various parts of plants, including fruits, are known for their therapeutic properties and are used in traditional medicine. Fruit species exhibit anticancer activities due to the presence of bioactive natural compounds such as flavonoids and carotenoids. The Vaccinium spp. are fleshy berry-like drupes and are rich in bioactive compounds, with flavonols, flavanols, chalcones, and phenolic acids as the major groups of compounds. While there is clear evidence linking Vaccinium berries with a decreased risk of BC both in in vivo and in vitro experiments, the exact mechanisms involved in the protective effects of Vaccinium spp. rich extracts on BC cells are not fully understood. 
  • 464
  • 15 Jan 2024
Topic Review
Adoptive T Cell Immunotherapy for Osteosarcoma
Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. 
  • 463
  • 28 Aug 2023
Topic Review
Cytochrome P450 Enzymes in Ovarian Cancers
There have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease’s development. 
  • 463
  • 10 Nov 2023
Topic Review
WD Repeat Domain 5 Inhibitors for Cancer Therapy
WDR5 is a conserved nuclear protein that scaffolds the assembly of epigenetic regulatory complexes and moonlights in functions ranging from recruiting MYC oncoproteins to chromatin to facilitating the integrity of mitosis. It is also a high-value target for anti-cancer therapies, with small molecule WDR5 inhibitors and degraders undergoing extensive preclinical assessment. WDR5 inhibitors were originally conceived as epigenetic modulators, proposed to inhibit cancer cells by reversing oncogenic patterns of histone H3 lysine 4 methylation—a notion that persists to this day.
  • 463
  • 15 Jan 2024
Topic Review
Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery
Due to their specificity, monoclonal antibodies have significantly impacted cancer patients’ care, becoming one of the fastest-growing classes of new drugs approved for the treatment of solid tumors. Targeted fluorescence-guided surgery is a novel technology to better visualize tumor residuals intraoperatively. It consists of a fluorescent molecular probe, that, once injected, lights up the neoplastic cells during the surgical resection. In this regard, the development of an off-the-shelf large-scale production of clinically approved, fluorescently labeled monoclonal antibodies for targeted fluorescence-guided surgery is becoming an urgent need for oncological surgeons working in this field.
  • 463
  • 15 Mar 2024
Topic Review
Involvement of SUV4-20H2 in Cancer
Histone lysine methyltransferase SUV4-20H2, a member of the suppressor of variegation 4–20 homolog (SUV4-20) family, has a critical impact on the regulation of chromatin structure and gene expression. This methyltransferase establishes the trimethylation of histone H4 lysine 20 (H4K20me3), a repressive histone mark that affects several cellular processes. Deregulated SUV4-20H2 activity has been associated with altered chromatin dynamics, leading to the misregulation of key genes involved in cell cycle control, apoptosis and DNA repair. Emerging research evidence indicates that SUV4-20H2 acts as a potential epigenetic modifier, contributing to the development and progression of several malignancies, including breast, colon and lung cancer, as well as renal, hepatocellular and pancreatic cancer.
  • 461
  • 08 Mar 2024
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