Purpose: SUM-IAP has been developed with the aim to optimize therapeutic response and minimize toxic reactions of oxazaphosphorine cytostatics. In therapy tests in mice, the primary tumor was successfully eradicated, but animals died due to formation of lethal metastases. We supposed that high activities of SUM-IAP detoxifying enzymes caused metastasis formation in the liver. Therefore, therapy tests with SUM-IAP in combination with cisplatin and N-methylformamide (NMF), which were not detoxified in the liver, were carried out.
Method: Antitumor activity was assayed in female CD2F1 mice with advanced subcutaneously growing P388 mice leukemia cells.
Result: The results of the therapy tests with SUM-IAP plus cisplatin were as expected: No formation of metastases and long-time survival of more than 100 days were observed; however, the toxicity was increased as measured by decrease in body weight and the number in leukocytes. The results of the tests in combination with NMF were surprising: Applying only half the dose of SUM-IAP used in the experiments with cisplatin, no metastases were found and long-time survivors did not show signs of additional toxicity.
Conclusion: NMF strongly enhances the antitumor activity of the oxazaphosphorine cytostatic SUM-IAP in mice with subcutaneously growing P388 mice leukemia cells by an unknown mechanism of action.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00432-016-2132-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Simultaneous Induction of Immunogenic Pyroptosis and PD-L1 Downregulation by One Single Photosensitizer for Synergistic Cancer Photoimmunotherapy.
J Med Chem
January 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P. R. China.
Pyroptosis, an excellent form of immunogenic cell death that can effectively activate antitumor immune responses, is attracting considerable interest as a promising approach for cancer immunotherapy. Immunogenic pyroptosis can recruit and stimulate dendritic cells to provoke further activation and tumor infiltration of T cells by releasing danger-associated molecular patterns, thus improving the tumor response to PD-1/PD-L1 checkpoint blockade immunotherapy. Here, we report the discovery of a bifunctional photosensitizer Nile Violet that can simultaneously trigger caspase-3/GSDME-mediated immunogenic pyroptosis and PD-L1 downregulation for cancer photoimmunotherapy.
View Article and Find Full Text PDFDiscovery of Novel Hydrazide-Based HDAC3 Inhibitors as Epigenetic Immunomodulators for Cancer Immunotherapy.
J Med Chem
January 2025
Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Based on our previous work, a series of imidazole-based small molecules were designed and synthesized as HDAC3 inhibitors. Among them, compound showed selective HDAC3 inhibition activity with an IC of 53 nM (SI = 75 for HDAC3 over HDAC1). Further studies revealed that could dose-dependently induce the expression of PD-L1 in MC38 cells by activating the PD-L1 transcription.
View Article and Find Full Text PDFMechanisms of Antitumor Activity of Low Doses of Radiation Associated with Activation of Cells' Defense System.
Dokl Biochem Biophys
January 2025
State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, 123098, Moscow, Russia.
Background: The effects of ionizing radiation (IR) involve a highly orchestrated series of events in cells, including DNA damage and repair, cell death, and changes in the level of proliferation associated with the stage of the cell cycle. A large number of existing studies in literature have examined the activity of genes and their regulators in mammalian cells in response to high doses of ionizing radiation. Although there are many studies, the research in effect of low doses of ionizing radiation remains limited.
View Article and Find Full Text PDFExploring novel immunotherapy in advanced esophageal squamous cell carcinoma: Is targeting TIGIT an answer?
Esophagus
January 2025
Department of Medical Oncology, National Taiwan University Cancer Center, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignancy in Asia. Recent advancements in immune checkpoint inhibitors (ICIs) have markedly transformed the systemic therapy landscape for ESCC. Anti-PD-1-based combination with chemotherapy or with ipilimumab, an anti-CTLA-4 antibody, have been established as the new standard first-line treatments for patients with advanced ESCC.
View Article and Find Full Text PDFNanoenzyme-based sensors for the detection of anti-tumor drugs.
Mikrochim Acta
January 2025
Public Health School, Mudanjiang Medical University, Mudanjiang, China.
Natural enzymes are a class of biological catalysts that can catalyze a specific substrate. Although natural enzymes have catalytic activity, they are susceptible to the influence of external environment such as temperature, and storage requirements are more stringent. Since the first discovery of magnetic FeO nanoparticles with peroxidase-like activity in 2007, the research on nanoenzymes has entered a rapid development stage.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!