The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia

Shizuka, Sato; Yamamoto, Eiko; Niimi, Keiko; Ino, Kazuhiko; Nishino, Kimihiro; Suzuki, Shiro; Kotani, Tomomi; Kajiyama, Hiroaki; Kikkawa, Fumitaka

doi:10.1007/s10147-019-01540-9

Cited by 24 publications

(23 citation statements)

References 22 publications

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“…We found that four of the hub genes (TOP2A, AURKA, NEK2, and RACGAP1) can serve as tumor therapeutic targets for drugs approved by FDA. Specifically, a set of TOP2A inhibitors were determined as potential chemoprotective drugs in various types of cancer, such as doxorubicin in solid tumors, leukemias and lymphomas [ 43 ], Idarubicin in HCC [ 44 ], acute myelogenous leukemia, advanced breast cancer, multiple myelom, non-Hodgkin's lymphoma, and other malignancies [ 45 ], and etoposide in several malignant tumors [ 46 – 50 ] and metastatic tumors (such as brain metastasis of breast cancer) [ 51 , 52 ]. Next, we identified candidate herbs and their effective components that may have an inhibitory impact on tumor progression via three hub genes (TOP2A, NUF2, and CCNB2).…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

Zhang

Tang

Guo

et al. 2021

Aging

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Section: Discussionmentioning

confidence: 99%

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

Zhang

Tang

Guo

et al. 2021

Aging

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“…It is probable that the mechanisms discussed above explain why ActD is the first line of treatment for different types of choriocarcinomas [ 14 ] and why it is useful in the therapy of rhabdomyosarcoma, Wilms tumor, Ewing’s sarcoma [ 12 , 13 ], and in the neoadjuvant therapy of hepatoblastoma [ 10 , 11 ]. The potential for effective clinical applications of this well-known drug reiterates the importance of research into its mechanism of action and the importance of identifying the genes that could provide resistance to it.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ActD has been shown to improve survival in preclinical models of recurrent glioblastoma [ 9 ]. Thus, the drug has been useful in the treatment of rare and highly aggressive cancers such as HB [ 10 , 11 ], embryonal sarcoma of the liver, Wilms tumor, rhabdomyosarcoma, Ewing’s disease, and choriocarcinoma [ 12 , 13 , 14 ]. Recent studies have revealed that ActD is cytotoxic to LCSCs without affecting immortalized normal hepatocytes [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Actinomycin D Arrests Cell Cycle of Hepatocellular Carcinoma Cell Lines and Induces p53-Dependent Cell Death: A Study of the Molecular Mechanism Involved in the Protective Effect of IRS-4

et al. 2021

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Actinomycin D (ActD) is an FDA-approved NCI oncology drug that specifically targets and downregulates stem cell transcription factors, which leads to a depletion of stem cells within the tumor bulk. Recently, our research group demonstrated the importance of IRS-4 in the development of liver cancer. In this study, we evaluated the protective effects of IRS-4 against ActD. For this study, three hepatocellular carcinoma cell lines (HepG2, Huh7, and Chang cells) were used to study the mechanism of actinomycin D. Most assays were carried out in the Hep G2 cell line, due to the high expression of stem cell biomarkers. We found that ActD caused HepG2 cell necroptosis characterized by DNA fragmentation, decreased mitochondrial membrane potential, cytochrome c depletion, and decreased the levels of reduced glutathione. However, we did not observe a clear increase in apoptosis markers such as annexin V presence, caspase 3 activation, or PARP fragmentation. ActD produced an activation of MAP kinases (ERK, p38, and JNK) and AKT. ActD-induced activation of AKT and MAP kinases produced an activation of the Rb-E2F cascade together with a blockage of cell cycle transitions, due to c-jun depletion. ActD led to the inhibition of pCdK1 and pH3 along with DNA fragmentation resulting in cell cycle arrest and the subsequent activation of p53-dependent cell death in the HepG2 cell line. Only JNK and AKT inhibitors were protective against the effects of ActD. N-Acetyl-L-cysteine also had a protective effect as it restored GSH levels. A likely mechanism for this is IRS-4 stimulating GCL-GSH and inhibiting the Brk-CHK1-p53 pathway. The assessment of the IRS-4 in cancer biopsies could be of interest to carry out a personalized treatment with ActD.

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“…However, in some females, HM remains prevalent and advances to a malignant nature that requires chemo-based treatment. [ 8 , 9 ]…”

Section: Introductionmentioning

confidence: 99%

Clinical assessment of prophylactic chemotherapy in treating with hydatidiform mole

Xu¹,

Zheng²,

Lu³

et al. 2021

Medicine

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Background: Hydatidiform mole (HM) is more common as molar pregnancy. It is a disease classified under the category of gestational trophoblastic diseases, which could metastasize after originating in the placenta. A majority of females suffering from molar pregnancies are curable by evacuating retained products of conception and the patient's fertility is preserved. In some cases, the growth perseveres and leads to gestational trophoblastic neoplasia, which is an extremely malicious condition that needs chemo-based treatment. There is a possibility to lessen the risk of gestational trophoblastic disease in females with HM through the administration of prophylactic chemo. Yet, there is controversy regarding prophylactic chemotherapy administered pre-or-post removal of HM to curtail the malignant sequelae. Therefore, we will conduct this research to assess both the efficacy as well as security of using prophylactic chemotherapy to treat HM. Methods: In the preliminary review, the authors will search for randomized controlled trials involving prophylactic chemotherapy to treat HM. The literature search is carried out in the following electronic databases from their inception to May 2021: Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database are the three Chinese language databases. Web of Science, PubMed, Cochrane Library, and EMBASE are the four English language databases. The authors will also perform a manual search through the bibliographies in related literature to find extra articles and ongoing studies. Two independent authors will assess the literature according to an inclusion criteria, use a specialized data collection table to extract data, and use the Cochrane ‘Risk of bias’ tool for evaluating any possible bias risk in the selected articles. Data synthesis and statistical operations are completed with the RevMan software (v. 5.3). Results: The present systematic analysis provides a rationalized synthesis of existing evidence related to the use of prophylactic chemotherapy in the treatment of HM. Conclusion: Our findings will summarize the current evidences for prophylactic chemotherapy in the treatment of HM. Ethics and dissemination: An ethics approval is nonrequired because pre published results will be used. Registration number: DOI 10.17605/OSF.IO/6QV52 ( https://osf.io/6qv52/ )

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The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia

Cited by 24 publications

References 22 publications

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

Actinomycin D Arrests Cell Cycle of Hepatocellular Carcinoma Cell Lines and Induces p53-Dependent Cell Death: A Study of the Molecular Mechanism Involved in the Protective Effect of IRS-4

Clinical assessment of prophylactic chemotherapy in treating with hydatidiform mole

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