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Topic Review
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Topic Review
Enzyme-Mediated Arginine Deprivation Agents for Cancer Therapy
Arginine is a semi-essential amino acid that supports protein synthesis to maintain cellular functions. Arginine also promotes wound healing, cell division, ammonia metabolism, immune system regulation, and hormone biosynthesis—all of which are critical for tumor growth. Several arginine deprivation strategies have been developed and entered clinical trials. The main principle behind these therapies is that arginine auxotrophic tumors rely on external arginine sources for growth because they carry reduced key arginine-synthesizing enzymes such as argininosuccinate synthase 1 (ASS1) in the intracellular arginine cycle. To obtain anticancer effects, modified arginine-degrading enzymes, such as PEGylated recombinant human arginase 1 (rhArg1-PEG) and arginine deiminase (ADI-PEG 20), have been developed and shown to be safe and effective in clinical trials. They have been tried as a monotherapy or in combination with other existing therapies.
316
17 Jul 2023
Topic Review
Etiological Factors of Acute on Chronic Liver Failure
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40–50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution.
440
17 Jul 2023
Topic Review
Myo/Nog Cells in the Lens
Myo/Nog cells, discovered by their expression of the skeletal muscle specific transcription factor MyoD, bone morphogenetic protein inhibitor Noggin, and brain specific angiogenesis inhibitor 1, are integrated into the eye during early stages of embryonic development. While their release of Noggin is critical normal eye morphogenesis, wounding may stimulate Myo/Nog cells to form contractile myofibroblasts that cause secondary cataracts and retinal detachment.
288
17 Jul 2023
Topic Review
Smartphone-Based Visual Inspection with Acetic Acid
Visual inspection with acetic acid (VIA) is recommended by the World Health Organization for primary cervical cancer screening or triage of human papillomavirus-positive women living in low-resource settings. Nonetheless, traditional VIA with the naked-eye is associated with large variabilities in the detection of pre-cancer and with a lack of quality control. Digital-VIA (D-VIA), using high definition cameras, allows magnification and zooming on transformation zones and suspicious cervical regions, as well as simultaneously compare native and post-VIA images in real-time. The available results to date show that the quality of D-VIA images is satisfactory and enables CIN1/CIN2+ diagnosis, and that a smartphone is a promising tool for cervical cancer screening monitoring and for on- and off-site supervision, and training. The use of artificial intelligence algorithms could soon allow automated and accurate cervical lesion detection.
226
17 Jul 2023
Topic Review
Subtypes of Triple Negative Breast Cancer
Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various molecular subtypes. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off-target toxicity are the primary hindrances to chemotherapeutic solutions for cancer.
395
17 Jul 2023
Topic Review
Drugs of the Kallikrein–Kinin System
The kallikrein–kinin system consists of the two kininogen substrates present in the blood plasma, and two serine proteases: the plasma and tissue kallikreins. The action of the latter on kininogens produces small peptides, the kinins, short-lived, but endowed by powerful pharmacologic actions on blood vessels and other tissues. Several classes of drugs alter kinin formation or action at their receptors for a therapeutic benefit.
539
17 Jul 2023
Topic Review
Phenotyping Cocktails Developed
Interethnic and interindividual variability in in vivo cytochrome P450 (CYP450)-dependent metabolism and altered drug absorption via expressed transport channels such as P-glycoprotein (P-gp) contribute to the adverse drug reactions, drug–drug interaction and therapeutic failure seen in clinical practice. A cost-effective phenotyping approach could be advantageous in providing real-time information on in vivo phenotypes to assist clinicians with individualized drug therapy, especially in resource-constrained countries such as South Africa.
280
17 Jul 2023
Topic Review
Tumor-Associated Carbohydrate Antigen-Targeted Immunotherapy
Glycosylation is one of the most pivotal post-translational modifications on all types of biomolecules for the formation of glycoproteins, glycolipids, and glycoRNAs in a tissue-type specific manner. Normal glycans participate in biological events such as development, metabolism, differentiation, and immunity in mammalian cells. In cancers, the altered glycosylation, known as tumor-associated carbohydrate antigens (TACAs), is specifically expressed on cell surface molecules and play important roles in facilitating tumor formation, progression, metastasis, and immunosurveillance evasion by generating the vulnerable tumor microenvironment through the interaction of glycan binding receptors expressed on immune cells. TACAs are potential tumor glyco-biomarkers, glycoimmune checkpoints, and therapeutics.
369
17 Jul 2023
Topic Review
Microbial Dysbiosis and α-Syn
Alpha-synuclein (α-Syn) is a short presynaptic protein with an active role on synaptic vesicle traffic and the neurotransmitter release and reuptake cycle. The α-Syn pathology intertwines with the formation of Lewy Bodies (multiprotein intraneuronal aggregations), which, combined with inflammatory events, define various α-synucleinopathies, such as Parkinson’s Disease (PD). The microbiota—which consists of thousands of bacterial, viral, and fungal species that inhabit different parts of the human body—plays a critical role in human health, not only through its barrier function against pathogens, but also through its regulatory role of the immune system as well as its impact on other important functions, such as the regulation of movement. The human gut microbiota in particular has been the focus of intense research. This microbiota is shaped by lifetime determinants (such as diet, disease history, age, or genetic heritance) and produces a variety of molecules, some of which can enter the bloodstream and affect overall systemic health.
315
17 Jul 2023
Topic Review
Peripheral Arterial Disease and Cardiologist
Peripheral artery disease (PAD) is a manifestation of systemic atherosclerotic disease. PAD patients have a poor prognosis with an increased risk of cardiovascular (CV) events, including myocardial infarction (MI), stroke, limb ischemia and CV death; therefore, it is important to detect and treat PAD early. PAD and coronary artery disease (CAD) share a common pathogenesis and risk factors for development; therefore, cardiologists are in a unique position to screen, diagnosis and treat PAD.
190
17 Jul 2023
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