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Topic Review
Lipids for Renal Cell Carcinoma Therapy
Kidney cancer is among the top ten most common cancers to date. Within the kidney, renal cell carcinoma (RCC) is the most common solid lesion occurring. Mutations in the von Hippel–Lindau gene (Vhl) have attracted a lot of interest since this gene regulates the hypoxia inducible transcription factors HIF-1α and HIF-2α, which in turn drive the transcription of many genes that are important for renal cancer growth and progression, including genes involved in lipid metabolism and signaling.
  • 393
  • 08 Mar 2023
Topic Review
Drug Delivery Systems for Age-Related Macular Degeneration
The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD.
  • 393
  • 15 Aug 2023
Topic Review
Volumetric Absorptive Microsampling
Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10–50 µL) within a few seconds (2–4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS).
  • 393
  • 28 Aug 2023
Topic Review
Cell-Penetrating Peptides Applications
Since their identification over twenty-five years ago, the plethora of cell-penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid in length peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger than themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor-specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell-activated forms. These methods are currently being used to image integrin-expressing tumors, breast cancer cells, human histiocytic lymphoma and protease-secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, antitumor antibodies and nanoparticles can be functionally attached to these peptides, leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue.
  • 392
  • 29 Jun 2021
Topic Review
3-Iodothyronamine and 3-Iodothyroacetic Acid
3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1) are thyroid-hormone-related compounds endowed with pharmacological activity through mechanisms that remain elusive. Some evidence suggests that they may have redox features.
  • 392
  • 21 Mar 2022
Topic Review
Single-Cell Analysis of Metallodrugs
Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest.
  • 391
  • 09 Sep 2021
Topic Review
Mechanistically Coupled PK (MCPK) Model of Dabrafenib Metabolism
Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and consequential relapse. A clinical drug-dose determination study shows increased pERK levels upon daily administration of more than 300 mg dabrafenib. To clarify whether such elevated drug concentrations could be reached by long-term drug accumulation, the pharmacokinetics (MCPK) of dabrafenib and its metabolites were mechanistically coupled. The MCPK model is qualitatively based on in vitro and quantitatively on clinical data to describe occupancy-dependent CYP3A4 enzyme induction, accumulation, and drug–drug interaction mechanisms. The prediction suggests an eight-fold increase in the steady-state concentration of potent desmethyl-dabrafenib and its inactive precursor carboxy-dabrafenib within four weeks upon 150 mg b.d. dabrafenib. While it is generally assumed that a higher dose is not critical, it was found experimentally that a high physiological dabrafenib concentration fails to induce cell death in embedded 451LU melanoma spheroids.
  • 390
  • 29 Jan 2022
Topic Review
Natural Products from Reniera Sponges
Reniera is one subgenus of Haliclona sponges and has a soft texture and brownish-maroon epidermis, and its body looks like a compressed tree with simple digitate branches and spicules of various sizes and harbors a special arrangement of the flagellated chambers in the incurrent and excurrent canal systems.
  • 389
  • 02 Jul 2021
Topic Review
Agrimonolide from Agrimonia pilosa Ledeb.
Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood–brain barrier. Interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent.
  • 388
  • 15 Feb 2023
Topic Review
Nanoparticles in the Intestinal Epithelial Cell Membrane
Intestinal epithelial cells are the most abundant epithelial cells in the intestine, accounting for 90–95% of intestinal cells. They are columnar cells with hair-like projections called microvilli on the apical membrane, which greatly increase the surface area available for absorption. The transintestinal cell pathway refers to the process in which nanoparticles pass through apical and basolateral membranes via intercellular transport and then discharge from the basement membrane to the extracellular space. The entire process can be divided into three stages: the uptake of nanoparticles in the apical membrane of intestinal epithelial cells, the transport of endosomes in the cytoplasm and the exocytosis of nanoparticles in the basement membrane.
  • 390
  • 05 Jul 2023
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