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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No studies are published on the use of dactinomycin use during pregnancy, but it is an FDA category C drug. Four normal infants (one set of twins) were born following Dactinomycin treatment in the second and/or third trimesters of pregnancy (Gililland and Weinstein, 1983); no exposures occurred during embryogenesis. Dactinomycin exposure was associated with an increased frequency of malformations in rodents born to mothers given doses several times the usual human dose (Manufacturer information). However, details of the congenital anomalies were not made available and the manufacturer’s product information is unpublished.
Endocrine tumors in pregnancy
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Prophylactic chemotherapy with methotrexate or dactinomycin at the time of pregnancy evacuation is not recommended or shown to decrease progression to GTN in low-risk patients.5 Prophylactic chemotherapy should only be considered in high-risk patients and in patients for whom adequate hCG monitoring cannot be performed.1
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The side effects of dactinomycin are similar to those of doxorubicin except that cardiotoxicity is less prominent. Tumor resistance to dactinomycin is common, possibly due to reduced uptake and/or active transport of the drug out of tumor cells.
Nucleophosmin 1: from its pathogenic role to a tantalizing therapeutic target in acute myeloid leukemia
Published in Hematology, 2022
Yuye Shi, Yuhao Xue, Chunling Wang, Liang Yu
Actinomycin D induces nucleolar oxidation, while NPM1 is S-glutathionylated at Cys275 under stress, further leading to its dissociation from rDNA/rRNA and translocation to the nucleoplasm, thus interfering with ribosomal biogenesis. TP53 mutations or 17p deletion do not frequently co-occur with NPM1 mutations in AML, thus, p53-mediated nucleolar stress still exists, and there is still a low-level expression of NPM1wt in the nucleoli of NPM1mut-cells. It is speculated that the nucleoli of NPM1mut-AML cells may be sensitive to medicines that trigger nucleolar stress (such as actinomycin D). Falini et al. reported that a newly diagnosed 60-year-old AML patient with NPM1mut and FLT3wt who could not undergo intensive chemotherapy due to heart disease responded to Actinomycin D. Later, Guillaume et al. reported that 3/17 (18%) of relapsed/refractory (R/R) adult AML carrying NPM1 mutation achieved CR after 1 course of actinomycin [9,63]. In another phase II single-centre clinical trial, 10 adult patients with R/R NPM1 mutated AML were treated with actinomycin. All patients responded to the treatment, with 44% achieving CR/CRi, with good treatment tolerance. Compared with NPM1wt cells, low-dose actinomycin displayed a more effective stress response in NPM1mut-cells, suggesting that NPM1 mutated AML was more sensitive to nucleolar stress. Therefore, actinomycin is a potential treatment option for R/R NPM1 mutated AML and warrants further investigation [64].
Circ_0000527 Drives Retinoblastoma Progression by Regulating miR-1236-3p/SMAD2 Pathway
Published in Current Eye Research, 2022
Ting Liang, Ming Fan, Zhaojun Meng, Bo Sun, Shuyong Mi, Xiangchun Gao
The expression of circ_0000527 in RB tissues and normal tissues was firstly investigated by qRT-PCR assay. The results showed that circ_0000527 was overexpressed in RB tissues compared to normal tissues (Figure 1a). Circ_0000527 level was increased in RB tissues with advanced TNM stages, positive optic nerve invasion and positive choroidal invasion (Figure 1b-d). Moreover, circ_0000527 was highly expressed in SO-Rb50 and Y79 cells compared to ARPE-19 cells (Figure 1e). Afterward, the feature of circ_0000527 was explored by RNase R assay and actinomycin D assay. As indicated by RNase R assay, FAM158A was digested by RNase R treatment, while circ_0000527 was resistant to RNase R (Figure 1f,g). Actinomycin D assay showed that the level of circ_0000527 was not affected and the level of FAM158A was markedly reduced in SO-Rb50 and Y79 cells treated with actinomycin D (Figure 1h,i). These results indicated that circ_0000527 was stable and might play a role in RB carcinogenesis.
Methotrexate induced peritonitis: diagnosis per exclusionem
Published in Journal of Obstetrics and Gynaecology, 2021
Raphaël Rienstra, Eva A.S. Koster, Catharina C.A.H. Janssen
Treatment with methotrexate is the first choice of treatment of persistent trophoblastic disease in the Netherlands. It is preferred to actinomycine-D because it is better tolerated by patients and shows better HCG disappearance rates (WOG 2017). We present a case of peritonitis induced by methotrexate therapy for trophoblastic disease which is often a diagnosis per exclusionem. It is accompanied by severe symptoms and therefore severe pathology has to be excluded. In this case report we describe the diagnostic work-up of abdominal pain during methotrexate therapy. Although persistent trophoblastic disease is rare (120 new cases a year in The Netherlands) it is important to understand the side effects of methotrexate. Especially since nowadays it is used more often as treatment for ectopic pregnancies.