Juvenile xanthogranuloma (JXG) is generally a benign, self-limited histiocytic disorder of the skin. We report two cases of multisystem JXG presenting with clinical features more commonly seen in Langerhans cell histiocytosis (LCH), including diabetes insipidus and lytic bony lesions. Histologically, the skin lesions demonstrated a histiocytic dermal infiltrate that stained for CD-68, but S-100 and CD1a stains were negative. Treatment according to LCH-based chemotherapy regimens resulted in prompt resolution of symptoms. A literature review of multisystem JXG cases treated with chemotherapy suggests that symptomatic patients can successfully be treated with LCH-based regimens that include both corticosteroids and vinca alkaloids.
Ifosfamide (IFO), which is used in the treatment of pediatric solid tumors, causes high rates of nephrotoxicity. N-acetylcysteine (NAC), an antidote for acetaminophen overdose, has been shown to prevent IFO-induced renal cell death and nephrotoxicity in both LLCPK-1 cells and a rat model. To facilitate the use of NAC in preventing IFO-induced nephrotoxicity in children, the authors compared the systemic exposure to NAC in children treated for acetaminophen overdose to the systemic exposure of the therapeutically effective rat model. The mean systemic exposure in the rat model was 18.72 mM·h (range, 9.92-30.02 mM·h), compared to the mean systemic exposure found in treated children (14.48 mM·h; range, 6.22-32.96 mM·h). They also report 2 pediatric cases in which NAC-attenuated acute renal failure associated with IFO when given concurrently with their chemotherapy treatment. Systemic exposure to NAC measured in 1 of these cases was comparable to that in the children treated for acetaminophen overdose. These results corroborate NAC's potential to protect against IFO-induced nephrotoxicity in children when used in its clinically approved dose schedule and supports a clinical trial in children.
In the last 2 decades, important advances in the treatment of Wilms' tumor have been made. The remarkable improvement in survival in these patients has been the product of new surgical techniques, classification of the tumors into prognostic stages upon initial presentation and the tailoring of chemotherapy and radiation therapy thus permitted. A brief historical perspective is presented with a review of the current treatment and ongoing studies.
Background:Nephrotoxicity is one of the known side effects of methotrexate (MTX) therapy despite the use of conventional protective measures. Our objectives were to evaluate the effects of N-acetylcysteine (NAC) on MTX-induced toxicity in renal tubular cells and to evaluate whether adjunctive use of NAC interferes with MTX antitumor activity in the B-cell lymphoma.Methods:Kidney Epithelial (Madin-Darby canine kidney [MDCK]) cells were exposed to MTX (10 μM or 100 μM) alone and with NAC (0.2 mM or 0.4 mM). Reactive oxygen species (ROS) generation at 1, 2, 4, and 24 h was measured by flow cytometer. Quantification of total glutathione (GSH) was performed by using GSH assay kit. To measure the impact of NAC on the antitumor activity of MTX, B lymphoma cells were exposed to MTX alone and with NAC. A percentage of apoptosis was measured using fluorescein isothiocyanate in both cell lines. Quantitative data was presented as a means ± standard deviation, and P values were analyzed using the Student's t-test.Results:Apoptosis in MDCK cells were observed after 24 h of incubation with both 10 μM and 100 μM MTX. Maximum ROS generation was observed at 4 h and corresponded to GSH production. Treatment with 0.2 and 0.4 mM of NAC led to decrease percentages of apoptotic MDCK cells. NAC did not change either proliferation or apoptosis of B-cell lymphoma.Conclusion:Using NAC for kidney protection may not interfere with the antitumor activity of MTX. Further in vivo studies are warranted to confirm noninterference between MTX and NAC and assess synergistic antitumor effects.
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