scholarly journals Preclinical trial of Bacteriosens used for the photodynamic therapyof malignant tumors, including prostate cancer

2018 ◽  
Vol 17 (3) ◽  
pp. 55-64 ◽  
Author(s):  
N. B. Morozova ◽  
E. A. Plotnikova ◽  
A. D. Plyutinskaya ◽  
V. O. Stramova ◽  
M. S. Vorontsova ◽  
...  

Introduction.Bacteriochlorins are the most promising photosensitizers absorbing in the near-infrared spectral region. Their use can enhance the efficiency of photodynamic therapy due to the deeper penetration of radiation into the tumor.Objectiveto conduct a preclinical study of the photoinduced antitumor activity and biodistribution of Bacteriosens.Materials and methods.Bacteriosens is a preparation based on meso-tetra(3-pyridyl)bacteriochlorin absorbing at 747 nm. Photoinduced cytotoxicity was investigated in vitro using human tumor cells: A549, Hep 2, BT-474, MCF-7, SK-BR-3, PC3, and EJ and murine tumor cells: S37, C26, and LLC. In vivo studies were performed in mice with large and small tumors (S37, LLC, and C26).Results.In vitro investigation show that bacteriosens during optical irradiation led to the effective suppression of tumor cell growth in culture (the IC50 value varied from 0,08μМ to 1,21 μМ) and had no toxicity without exposure to light. The effective photodynamic therapy regimen using Bacteriosens in mice with inoculated small and large tumors of different genesis resulted in regression of a primary tumor node on 90–100 % of the animals in the absence of tumor recurrence within 90 days after treatment.Conclusion.Bacteriosens is a promising agent for the photodynamic therapy of small and large tumors; it can be successfully used as an alternative, organ-sparing minimally invasive treatment for malignant tumors, including prostate cancer.

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 205-205
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Dalia Martinez-Marin ◽  
Stephanie Filleur

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.


Author(s):  
Beata Osiecka ◽  
Kamil Jurczyszyn ◽  
Krzysztof Symonowicz ◽  
Andrzej Bronowicz ◽  
Paweł Ostasiewicz ◽  
...  

AbstractPhotodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.


2010 ◽  
Vol 8 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Jessica J. Huck ◽  
Mengkun Zhang ◽  
Alice McDonald ◽  
Doug Bowman ◽  
Kara M. Hoar ◽  
...  

2001 ◽  
Vol 204 (2) ◽  
pp. 217-227
Author(s):  
J.A. Albertus ◽  
R.O. Laine

Many aquatic organisms are resistant to environmental pollutants, probably because their inherent multi-drug-resistant protein extrusion pump (pgp) can be co-opted to handle man-made pollutants. This mechanism of multixenobiotic resistance is similar to the mechanism of multidrug resistance exhibited in chemotherapy-resistant human tumor cells. In the present study, a variety of techniques were used to characterize this toxin defense system in killifish (Fundulus heteroclitus) hepatocytes. The cellular localization and activity of the putative drug efflux system were evaluated. In addition, in vitro and in vivo studies were used to examine the range of expression of this putative drug transporter in the presence of environmental and chemotherapeutic toxins. The broad range of pgp expression generally observed in transformed mammalian cells was found in normal cells of our teleost model. Our findings suggest that the expression of the pgp gene in the killifish could be an excellent indicator of toxin levels or stressors in the environment.


2020 ◽  
Vol 57 ◽  
pp. 101715 ◽  
Author(s):  
Iman Akbarzadeh ◽  
Mohammad Tavakkoli Yaraki ◽  
Mahsa Bourbour ◽  
Hassan Noorbazargan ◽  
Aseman Lajevardi ◽  
...  

2017 ◽  
Vol 22 (1) ◽  
pp. 4-14
Author(s):  
H. M Treshalina ◽  
G. B Smirnova ◽  
S. A Tsurkan ◽  
J. R Tcherkassova ◽  
N. A Lesnaya

There was executed the analysis of thematic literature during from 1956 to 2015 devoted to receptors to fetal proteins, including to alpha-fetoprotein (AFP) known in medicine as oncomarker and used by malignant cells for the organization of tumoral homeostasis. As protein carrier, AFP similar to albumin takes of vitally important molecules in a space «hydrophobic pocket» and moves inside a cell, but as the cancer-embryonal antigen (CEA) - determines the existence of a malignant tumor, but not the type of a neoplasm. On the bounding of AFP with teratogen and their internalization and delivery in an embryo there is based the development of ways of «address» delivery of substances into a cell. This is realized by means of receptor mediated endocytosis via specific membranous receptors to AFP (ReCAF) with high selectivity concerning malignant cells of various genesis. Up to 90% of all malignant cells of the human and tumor models for human and mammalians express AFP receptors, including rather recently opened stem tumor cells - the most probable source of metastasing. AFP production and expression of receptors is selectively raised in malignant tumors of patients and human tumor models. The hyperproduction of AFP and hyperexpression of ReCAF are related to the histologic type of tumor model and are characteristic for embrional cell tumors and hepatoblastomas with initially low drug sensitivity or with the resistance. When choosing the model it is necessary to consider that in different types of tumor cells ReCAF have specific features in cultivation which are not pronounced in conditions of an animal organism. More differentiated tumors are characterized by the larger level of the AFP production and a hyperexpression of ReCAF. The use of subcutaneous tumor xenografts signal for AFP localizations with the hyperexpression of receptors, allows to reveal mostly evidentially the effectiveness of the therapeutic system at the preclinical level. Address delivery of therapeutic systems created on the basis of AFP or its fragments is capable of causing the change of their pharmacological properties. The therapeutic prize is possible due to the induction of process of apoptosis via the mitochondrial pathway, but at the same time the fall in the cytotoxic capacity of system is possible.


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