Analysis of different therapeutic schemes combining cyclophosphamide and doublestranded DNA preparation for eradication of Krebs-2 primary ascites in mice

Potter, Amiee; Долгова, В.; Минкевич, М.; Николин, П.; Попова, А. С.; Ефремов, Р.; Байбородин, И.; Rogachev, Artem D.; Проскурина, С.; Козел, В.; Таранов, С.; Омигов, В. В.; Верещагин, И.; Petrov, Borislav; Останин, А. А.; Черных, Р.; Колчанов, А.; Bogachev, Sergey S.

doi:10.18699/vj15.117

Cited by 3 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increased percentage of this type of cells over the background of a drastic decrease in the number of committed tumor cells (the bulk of tumor cells) testified for exactly the such events flow. This finding denoted the most important time point in the therapy, when all remaining tumor cells, both committed and stem-like, are synchronized in G2/M phases [29][30][31][32][33].…”

Section: Brief History and Main Stages Of The "Karanahan" Developmentmentioning

confidence: 74%

Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model

Ruzanova

Proskurina

Efremov

et al. 2022

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Background and Aims: A new technology based on the chronometric administration of cyclophosphamide and complex composite double-stranded DNA-based compound, which is scheduled in strict dependence on interstrand crosslinks repair timing, and named “Karanahan”, has been developed. Being applied, this technology results in the eradication of tumor-initiating stem cells and full-scale apoptosis of committed tumor cells. In the present study, the efficacy of this novel approach has been estimated in the model of Lewis carcinoma.Methods: To determine the basic indicative parameters for the approach, the duration of DNA repair in tumor cells, as well as their distribution along the cell cycle, have been assessed. Injections were done into one or both tumors in femoral region of the engrafted mice in accordance with the developed regimen. Four series of experiments were carried out at different periods of time. The content of poorly differentiated CD34+/TAMRA+ cells in the bone marrow and peripheral blood has been determined. Immunostaining followed by the flow cytometry was used to analyze the subpopulations of immune cells.Results: The high antitumor efficacy of the new technology against the developed experimental Lewis carcinoma was shown. It was found that the therapy efficacy depended on the number of tumor growth sites, seasonal and annual peculiarities. In some experiments, a long-term remission has been reached in 70% of animals with a single tumor and in 60% with two tumors. In mice with two developed grafts, mobilization capabilities of both poorly differentiated hematopoietic cells of the host and tumor stem-like cells decrease significantly. Being applied, this new technology was shown to activate a specific immune response. There is an increase in the number of NK cell populations in the blood, tumor, and spleen, killer T cells and T helper cells in the tumor and spleen, CD11b+Ly-6C+ and CD11b+Ly-6G+ cells in the tumor. A population of mature dendritic cells is found in the tumor.Conclusion: The performed experiments indicate the efficacy of the Karanahan approach against incurable Lewis carcinoma. Thus, the discussed therapy is a new approach for treating experimental neoplasms, which has a potential as a personalized anti-tumor therapeutic approach in humans.

show abstract

Section: Brief History and Main Stages Of The "Karanahan" Developmentmentioning

confidence: 74%

Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model

Ruzanova

Proskurina

Efremov

et al. 2022

Pathol. Oncol. Res.

View full text Add to dashboard Cite

show abstract

“…In the mouse models we have used, the process of DNA repair in the investigated tumor cell lines did not overlap with that in normal hematopoietic cells that allowed using the Karanahan approach with no limitations 26 . If such an overlap is detected in clinical settings, the symptom complex of “death window” is to be resolved by the reinfusion of preserved bone marrow hematopoietic cells taken before the start of therapy 28 , 49 . Another possible approach is the use of antibiotics (or any other affordable ways) for suppressing opportunistic infections during the time span required for the restoration of functional immune response 45 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of the new therapeutic approach in curing malignant neoplasms on the model of human glioblastoma

et al. 2021

View full text Add to dashboard Cite

“…In clinical specimens of human mammary gland cancer, TAMRA+ cells made up ~10 to ~30% of the CD44+/CD24-CSCs (unpublished data). (30,31,(48)(49)(50)(51). In our early studies, we focused on the synergistic effect of CP and dsDNA against CD34+/TAMRA+ hematopoietic cells from the bone marrow and CD34+/TAMRA+ stem cells of Krebs-2 in vivo.…”

Section: Tamra+ Cells Represent a Variety Of Poorly Differentiated Ce...mentioning

confidence: 99%

“…crosslinking cytostatic CP at a dose of 100 mg/kg of animal weight and with complex composite dsDNA preparation at a dose of 0.5 mg/mouse. bulk of tumor cells (49). Additionally, we monitored the content of CD34+ cells (95% of which are TAMRA-positive) in ascites along the treatment.…”

Section: Figure 2 Determination Of Time Parameters For "Karanahan" (C...mentioning

confidence: 99%

Experimental Comparison of the In Vivo Efficacy of Two Novel Anticancer Therapies

et al. 2021

View full text Add to dashboard Cite

Background/Aim: We compared the therapeutic efficacy of two recently developed experimental anticancer technologies: 1) in situ vaccination based on local immunotherapy with CpG oligonucleotides and anti-OX40 antibodies to activate antitumor immune response and 2) "Karanahan" technology [from the Sanskrit kāraṇa ('source') + han ('to kill')] based on the combined injection of cyclophosphamide and double-stranded DNA to eradicate cancer stem cells. Materials and Methods: The anticancer approaches were compared on three types of mouse malignant tumors with different grades of immunogenicity: weakly immunogenic carcinoma Krebs-2, moderately immunogenic Lewis carcinoma, and highly immunogenic A20 В-cellular lymphoma. Results: Our results indicated that in situ vaccination was the most effective against the highly immunogenic tumor А20. In addition, "Karanahan" demonstrated high efficiency in all types of tumors, regardless of their immunogenicity or size. Conclusion: "Karanahan" therapy showed higher efficacy relative to in situ vaccination with CpG oligonucleotides and anti-OX40 antibodies.

show abstract

Analysis of different therapeutic schemes combining cyclophosphamide and doublestranded DNA preparation for eradication of Krebs-2 primary ascites in mice

Cited by 3 publications

References 15 publications

Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model

Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model

Efficacy of the new therapeutic approach in curing malignant neoplasms on the model of human glioblastoma

Experimental Comparison of the In Vivo Efficacy of Two Novel Anticancer Therapies

Contact Info

Product

Resources

About