Monoclonal antibodies (mAbs) are critical components in the therapeutic landscape, but their dosing strategies often evolve post-approval as new data emerge. This review evaluates post-marketing label changes in dosing information for FDA-approved mAbs from January 2015 to September 2024, with a focus on both initial and extended indications. We systematically analyzed dosing modifications, categorizing them into six predefined groups: Dose increases or decreases, inclusion of new patient populations by body weight or age, shifts from body weight-based dosing to fixed regimens, and adjustments in infusion rates.
View Article and Find Full Text PDFUrinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021.
View Article and Find Full Text PDFIntroduction: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC).
Materials And Methods: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS).
Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted.
Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses.
In multipolar nigral dopamine (DA) neurons, the highly excitable proximal dendritic compartments (PDCs) and two Na -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. However, the causal link between them is unknown. Here we report that the proximal dendritic localization of NALCN underlies pacemaking and burst firing in DA neurons.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2022
Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca-dependent manner. The source of Ca and the molecular mechanism by which Ca is provided for this process are not known. The intracellular Ca permeable channel transient receptor potential mucolipin 3 (TRPML3) localizes in the autophagosome and interacts with the mammalian autophagy-related protein 8 (ATG8) homolog GATE16.
View Article and Find Full Text PDFBacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment.
View Article and Find Full Text PDFPurpose: Endothelin-1 (ET-1) is a potent vasoconstrictor which seems to be involved in the pathogenesis of diabetic retinopathy (DR). However, studies on intraocular ET-1 in DR have been limited. Thus, we investigated aqueous ET-1 levels in patients with DR.
View Article and Find Full Text PDFBackground: Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer.
Methods: Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23 kg/m), "overweight" (23-27.
Background: Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time.
View Article and Find Full Text PDFMidbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown.
View Article and Find Full Text PDFPurpose: To investigate aqueous humor concentrations of endothelin-1 (ET-1) in patients with central retinal vein occlusion (CRVO) compared with patients with branch retinal vein occlusion (BRVO) and a normal control group.
Methods: A total 80 subjects were included in this prospective study, including 15 patients with CRVO, 20 patients with BRVO, and 45 patients who underwent cataract surgery and had no concomitant ocular disease. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month.
High expression of glucose transporter family members, which augment glucose uptake and glycolytic flux, has been shown to play a pivotal role in the proliferation and survival of tumor cells, contributing to the energy supply, biosynthesis and homeostasis of cancer cells. Among the many members, solute carrier family 2 member 1 (SLC2A1) encodes a glucose transporter, GLUT1, that is critical in the metabolism of glucose, which is an energy source for cell growth that contributes to cancer progression and development. The aim of this study was to analyze the survival and genetic changes/immune profiles in patients with gastric cancer with high SLC2A1 expression and to provide treatment for improving prognosis.
View Article and Find Full Text PDFTo date, many population pharmacokinetic models of antibiotics have been developed using blood sampling data after the fourth or fifth dose, which represents steady-state levels. However, if a model developed using blood sampled after the first dose is equivalent to that using blood sampled after the fourth dose, it would be advantageous to utilize the former. The aim of this study was to investigate the effect of blood sampling after the first and/or fourth drug administration on the accuracy and precision of parameter estimates.
View Article and Find Full Text PDFBackground: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of . The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance.
Methods: A total of 46 strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy.
Background And Purpose: NALCN is a Na leak, GPCR-activated channel that regulates the resting membrane potential and neuronal excitability. Despite numerous possible roles for NALCN in both normal physiology and disease processes, lack of specific blockers hampers further investigation.
Experimental Approach: The effect of N-benzhydryl quinuclidine compounds on NALCN channels was demonstrated using whole-cell patch-clamp recordings in HEK293T cells overexpressing NALCN and acutely isolated nigral dopaminergic neurons that express NALCN endogenously.
Tomato spotted wilt virus (TSWV), transmitted by small insects known as thrips, is one of the major threats to tomato productivity across the globe. In addition to tomato, this virus infects more than 1000 other plants belonging to 85 families and is a cause of serious concern. Very little, however, is known about the molecular mechanism of TSWV induced signaling in plants.
View Article and Find Full Text PDFAims: Several studies have reported that critically ill patients who require amikacin for the treatment of severe infection require therapeutic drug monitoring (TDM) to prevent acute kidney injury. Moreover, studies so far have mainly focused on patients with critical illnesses; therefore, the probability of occurrence of nephrotoxicity in noncritically ill patients is less known and tends to be overestimated. Recently, with the emergence of multidrug resistant bacteria, the need for aminoglycosides has resurfaced.
View Article and Find Full Text PDFWHAT IS KNOWN AND OBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established.
View Article and Find Full Text PDFObjective: The first aim of this study was to compare the predictability of efficacy by Monte Carlo simulation between a true one-compartment model and a true two-compartment model for doripenem. The second aim was to explore how we can identify the usefulness of a one-compartment model when the pharmacokinetic/pharmacodynamic (PK/PD) indices between three misspecified one-compartment models and a true two-compartment model are compared.
Materials And Methods: The reported two-compartment model parameters of two doripenem studies and a vancomycin study were used to generate 200 virtual concentration-time profiles for each study.
Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors.
View Article and Find Full Text PDFBackground: Ginseng is one of the well-known medicinal plants, exhibiting diverse medicinal effects. Its roots possess anticancer and antiaging properties and are being used in the medical systems of East Asian countries. It is grown in low-light and low-temperature conditions, and its growth is strongly inhibited at temperatures above 25°C.
View Article and Find Full Text PDFMCOLN3/TRPML3 is a Ca-permeable cation channel that is expressed in multiple subcellular compartments with dynamic localization. Our previous studies suggest that upon macroautophagy/autophagy induction MCOLN3/TRPML3 is recruited and provides Ca for the fusion process in autophagosome biogenesis. However, how intracellular trafficking and the Ca channel function of MCOLN3/TRPML3 are related to autophagy are not known.
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