scholarly journals Therapeutic efficacy and artemisinin resistance in northern Myanmar: evidence from in vivo and molecular marker studies

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Moe Kyaw Myint ◽  
Charlotte Rasmussen ◽  
Aung Thi ◽  
Dorina Bustos ◽  
Pascal Ringwald ◽  
...  
2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Youssouf Diarra ◽  
Oumar Koné ◽  
Lansana Sangaré ◽  
Lassina Doumbia ◽  
Dade Bouye Ben Haidara ◽  
...  

Abstract Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2000–200,000 asexual parasites/μL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42. were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. Results A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI 78.5–88.4%) in the AL arm and 93.1% (95% CI 89.7–96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0–95.9%) in the AL arm and 97.1% (93.6–100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. Conclusions The findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Wang ◽  
Ke-Chun Wu ◽  
Bing-Xiang Zhao ◽  
Xin Zhao ◽  
Xin Wang ◽  
...  

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution,in vivoantitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P<.01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Tien-Hung Huang ◽  
Cheuk-Kwan Sun ◽  
Yi-Ling Chen ◽  
Pei-Hsun Sung ◽  
Chi-Hsiang Chu ◽  
...  

Background. This study was aimed at testing the association between the therapeutic efficacy of CD34+ cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). Methods. Angiographic grades (0: <5%; 1: 5–35%; 2: 35–75%; 3: >75%) which presented the improvement of vessel density pre- and post-CD34+ treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34+ cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n=12) and high-score group (angiographic grade 2 or 3, n=18). The percentages of circulating EPCs with KDR+/CD34+/CD45−, CD133+/CD34+/CD45−, and CD34+ were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. Results and Conclusions. The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p=0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p=0.027). The area under the ROC curve (AUC) was 0.8519 (p=0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34+ cell treatment.


Cancer ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 1862-1868 ◽  
Author(s):  
Andrew J. Vickers ◽  
Kwang Jang ◽  
Daniel Sargent ◽  
Hans Lilja ◽  
Michael W. Kattan

2007 ◽  
Vol 67 (8) ◽  
pp. 3818-3826 ◽  
Author(s):  
Sanjeev Banerjee ◽  
Maha Hussain ◽  
Zhiwei Wang ◽  
Allen Saliganan ◽  
Mingxin Che ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mylène Tajan ◽  
Marc Hennequart ◽  
Eric C. Cheung ◽  
Fabio Zani ◽  
Andreas K. Hock ◽  
...  

AbstractMany tumour cells show dependence on exogenous serine and dietary serine and glycine starvation can inhibit the growth of these cancers and extend survival in mice. However, numerous mechanisms promote resistance to this therapeutic approach, including enhanced expression of the de novo serine synthesis pathway (SSP) enzymes or activation of oncogenes that drive enhanced serine synthesis. Here we show that inhibition of PHGDH, the first step in the SSP, cooperates with serine and glycine depletion to inhibit one-carbon metabolism and cancer growth. In vitro, inhibition of PHGDH combined with serine starvation leads to a defect in global protein synthesis, which blocks the activation of an ATF-4 response and more broadly impacts the protective stress response to amino acid depletion. In vivo, the combination of diet and inhibitor shows therapeutic efficacy against tumours that are resistant to diet or drug alone, with evidence of reduced one-carbon availability. However, the defect in ATF4-response seen in vitro following complete depletion of available serine is not seen in mice, where dietary serine and glycine depletion and treatment with the PHGDH inhibitor lower but do not eliminate serine. Our results indicate that inhibition of PHGDH will augment the therapeutic efficacy of a serine depleted diet.


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