scholarly journals BIOPREPARATION FOR IN SITU ANTITUMOR VACCINATION

ASJ. ◽  
2021 ◽  
Vol 2 (45) ◽  
pp. 4-7
Author(s):  
A. Zinchenko ◽  
L. Birichevskaya ◽  
A, Shchokolova ◽  
P. Krasochko ◽  
A. Barashkov

The present study is focused on the first attempt to use an enzymatically produced biological preparation of cyclic diguanosine monophosphate (cyclic di-GMP) for the therapy of animal cancer. Feline breast carcinoma was chosen as the test model. The preparation was administered intratumorally to induce the immunogenic death of a part of the cancer cells and thus carry out the so-called in situ antitumor vaccination. Preliminary results indicate good therapeutic prospects of studied biopreparation for animal cancer treatment. In conclusion, the expedience of further trials of cyclic di-GMP preparation for in situ antitumor vaccination was stated. The need to supplement this mono-preparation with another immunostimulating adjuvant characterized by a mechanism of action distinct from that exhibited by cyclic di-GMP was emphasized. DNA preparation comprising the so-called immunostimulating CpG motifs was provided as an example of such compound. 

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3632-3632
Author(s):  
Aurélie Rousseau ◽  
Patrick Van Dreden ◽  
Elisabeth Mbemba ◽  
Mohamed Hatmi ◽  
Amir Kharterchi ◽  
...  

Abstract Introduction The optimization of the antithrombotic treatment with LMWH (enoxaparin), direct and indirect anti-Xa ( Apixaban, fondaparinux), in patients with adenocarcinoma of the pancreas, or human breast carcinoma is a challenging issue. The understanding of their mechanism of action in cancer-induced hypercoagulability might provide evidence for treatment optimization. To this aim, we studied the influence of pancreas adenocarcinoma cells (BXPC3), or human breast carcinoma cells (MCF7) on the antithrombotic activity of enoxaparin, fondaparinux and apixaban. Materials and Methods Cells were cultured and adhered in 96-well plates (50cells/µl). Thrombin generation (TG) of normal platelet poor plasma spiked with clinically relevant concentrations of enoxaparin, fondaparinux and apixaban which was added in wells carrying cancer cells was assessed with the Calibrated Automated Thrombogram assay. In the control experiment TG was triggered using PPP-Reagent 5 pM TF. The lag-time of thrombin generation, the maximum concentration of thrombin (Peak), and the mean rate index (MRI) of the propagation phase of thrombin generation were analysed [MRI=Peak/(ttPeak-lag-time)]. The IC50 of the studied compounds were calculated by extrapolation from the concentration-response curve, and compared. Results All studied antithrombotic agents inhibited in a concentration dependent manner the thrombin generation. The three studied agents significantly inhibited TG at plasma concentrations usually achieved at doses for thromboprophylaxis. However the presence of cancer cells and their type was determinant for the antithrombotic potency of the studied drugs. Comparison on the basis of IC50 showed that the presence of either BXPC3 or MCF7 cells did not significantly modify the antithrombotic potency of enoxaparin as compared to the control experiment. In contrast the inhibitory effect of fondaparinux and apixaban on thrombin generation was partially reversed when TG was triggered by BXPC3 since the IC50 were significantly increased as compared to the control experiment. The presence of MCF7 cells did not significantly modify the antithrombotic activity of apixaban and fondaparinux. Conclusions The LMWH enoxaparin and the specific FXa inhibitors apixaban and fondaparinux demonstrate potent inhibitory capacity on thrombin generation triggered by cancer cells. The type of cancer cells is determinant for the antithrombotic efficiency of the specific factor Xa inhibitors independently of their mechanism of action (i.e. antithrombin dependent or independent inhibition of FXa). In contrast the type of cancer cells does not significantly influence the potency of enoxaparin. This is probably due to the presence of the trace amounts of anti-IIa activity. The present study stresses out that the impact of the type of cancer cells on the antithrombotic activity of the specific Xa inhibitors should not be neglected. These data have to be taken into consideration for the design of dose-finding studies of the direct orally active FXa inhibitors in patients with different histological types of cancer. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Xia Ling ◽  
Letao Huang ◽  
Youzhen Li ◽  
Qing Wan ◽  
Zhiming Wang ◽  
...  

Chemotherapeutics with systemic administration usually suffer from low treatment efficacy and off-target toxicity. In contrary, the photoactivatable cancer theranostics can achieve image-guided precise control of therapeutic dose and location. However, the conventional photoactivatable chemotherapeutics usually require decoration of chemotherapeutics with additional photo-responsive groups through tedious synthetic procedures, which can lead to undesirable toxic byproducts and seriously restrict their applications. Herein, we propose a new strategy for photoactivatable caner theranostics based on photooxidative dehydrogenation reaction, which is only associating with water as the byproduct. To demonstrate the power of this strategy, we utilized the natural dihydrobenzo[c]phenanthridine alkaloids of DHCHE and DHSAN as photoactivatable theranostics to achieve selective imaging and killing of cancer cells by in situ transformation into nucleus-targeted CHE and SAN under light irradiation. Notably, CHE is featured with aggregation-induced emission (AIE) characteristics, which can be used for precise control of the photoactivatable therapeutic dose. This photoactivatable strategy based on dihydroalkaloids is thus promising for precise cancer treatment in clinic.<br>


2020 ◽  
Author(s):  
Xia Ling ◽  
Letao Huang ◽  
Youzhen Li ◽  
Qing Wan ◽  
Zhiming Wang ◽  
...  

Chemotherapeutics with systemic administration usually suffer from low treatment efficacy and off-target toxicity. In contrary, the photoactivatable cancer theranostics can achieve image-guided precise control of therapeutic dose and location. However, the conventional photoactivatable chemotherapeutics usually require decoration of chemotherapeutics with additional photo-responsive groups through tedious synthetic procedures, which can lead to undesirable toxic byproducts and seriously restrict their applications. Herein, we propose a new strategy for photoactivatable caner theranostics based on photooxidative dehydrogenation reaction, which is only associating with water as the byproduct. To demonstrate the power of this strategy, we utilized the natural dihydrobenzo[c]phenanthridine alkaloids of DHCHE and DHSAN as photoactivatable theranostics to achieve selective imaging and killing of cancer cells by in situ transformation into nucleus-targeted CHE and SAN under light irradiation. Notably, CHE is featured with aggregation-induced emission (AIE) characteristics, which can be used for precise control of the photoactivatable therapeutic dose. This photoactivatable strategy based on dihydroalkaloids is thus promising for precise cancer treatment in clinic.<br>


2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.


2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.


Nanoscale ◽  
2021 ◽  
Author(s):  
Jianqin Yan ◽  
Zhuangzhuang Zhang ◽  
xiaohui Zhan ◽  
Keqi Chen ◽  
Yuji Pu ◽  
...  

mproving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was...


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