China
Africa
Explore chapters and articles related to this topic
Miltefosine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Andrew Stewardson, Douglas Johnson
Given its poor tolerability at oral dosages required for cancer chemotherapy, miltefosine has been principally used as topical treatment for skin metastases of breast cancer and cutaneous lymphoma. A review concluded that in breast cancer patients, the application of 6% miltefosine solution applied topically to superficial fungating breast lesions (smaller than 1 cm) may slow disease progression in those who have received prior radiotherapy, surgery, hormonal therapy, or chemotherapy (Adderley and Holt, 2014). Clinical prospects for alkylphosphocholines in cancer management are discussed elsewhere (van Blitterswijk and Verheij; 2008; Pachioni Jde et al., 2013).
Enhancing the in vitro and in vivo activity of itraconazole against breast cancer using miltefosine-modified lipid nanocapsules
Published in Drug Delivery, 2021
Nabila A. El-Sheridy, Riham M. El-Moslemany, Alyaa A. Ramadan, Maged W. Helmy, Labiba K. El-Khordagui
To validate the in vitro and in vivo results obtained, the level of three tumor biomarkers, Gli1, caspase-3, and VEGF was assessed quantitatively in the tumor tissue. Gli1 protein is the final transcriptional effector of the Hh signaling pathway, recognized as an indicator of tumor progression and metastasis (Wang et al., 2017a; Xie et al., 2019). As shown in Figure 7(A), tumors of untreated mice had the largest content of Gli1 which was significantly (≈76%, p < .05) reduced by Dox. A significant reduction in Gli 1 expression was also induced by ITC-sol (≈51.7%, p < .05). ITC is a potent inhibitor of the Hh pathway via a complex signaling cascade culminating into suppression of the Gli family of transcription factors leading to multiple anticancer effects including apoptosis and tumor growth inhibition (Li et al., 2019; Wei et al., 2020). Although LNC did not significantly enhance the ITC effect, the decrease in Gli1 (≈58%) by M-ITC-LNC was significantly different from that of ITC-sol, pointing to an MFS enhancing effect. A structurally related alkylphosphocholine, perifosine, was reported to suppress Hh signaling by inhibiting Gli 1 activation and decreasing its target protein patched 1 expression (Xin et al., 2014).
Novel treatment strategies and drugs in development for cryptosporidiosis
Published in Expert Review of Anti-infective Therapy, 2018
Miguel A Chavez, A Clinton White
Oleylphosphocholine (OlPC) is structurally related to the antiparasitic drug miltefosine (both are alkylphosphocholines). OlPC is suspected to act similarly to miltefosine interfering with parasitic lipid biosynthesis and cellular membrane integrity while inducing apoptosis of the parasite [47]. In a study that terminated prematurely, Miltefosine showed poor efficacy and severe adverse events among Zambian adults with HIV-related cryptosporidiosis [48]. OlPC, on the other hand, is already in development for leishmaniasis and has shown good tolerability in mouse models [49]. Sonzogni-Desautels et al. [50] tested this compound in vivo and in vitro against Cryptosporidium spp. They found that OlPC inhibited C. parvum infection of HCT-8 cells and was able to cure lethal infection of C. parvum in mice. There was no evidence of relapse at 30 days. OlPC showed better toxicity profile on HCT-8 cells compared to miltefosine.
Heme metabolism as a therapeutic target against protozoan parasites
Published in Journal of Drug Targeting, 2019
Guilherme Curty Lechuga, Mirian C. S. Pereira, Saulo C. Bourguignon
Miltefosine, an alkylphosphocholine anti-cancer drug, acts against Leishmania by increasing ROS which leads to apoptosis-like cell death, and also acts as host immunomodulatory factor [140]. Patients with VL had increased levels of HO-1, as well as, Nrf-2 nuclear translocation, serum bilirubin, glutathione peroxidase and superoxide dismutase (SOD) activity. It appears that miltefosine acts regulating HO-1/Nrf-2-mediated oxidative responses in VL decreasing the levels of these substances and inducing ROS [141]. These data show that HO-1 represents an important mechanism for Leishmania protection and proliferation. Thus, it turns out a potential therapeutic target and a biomarker for VL.