&lt;em&gt;BCG&lt;/em&gt; and &lt;em&gt;IL&lt;/em&gt; − 2 model for bladder cancer treatment with fast and slow dynamics based on &lt;em&gt;SPVF&lt;/em&gt; method—stability analysis

Nave, Ophir; Hareli, Shlomo; Elbaz, Miriam; Iluz, Itzhak Hayim; Bunimovich‐Mendrazitsky, Svetlana

doi:10.3934/mbe.2019267

Cited by 17 publications

(5 citation statements)

References 30 publications

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“…Therefore, in vivo experiments will be required to be conducted in a future study. In addition, bioinformatic analysis such as BCG and IL-2 models for bladder cancer treatment [ 55 ] could also be useful. The results of our study and observation are in concordance with similar studies [ 56 , 57 , 58 ], and this approach presents a rationale to overcome drug resistance from an autophagy perspective.…”

Section: Discussionmentioning

confidence: 99%

Targeting Pro-Survival Autophagy Enhanced GSK-3β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells

et al. 2023

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Advanced bladder cancer (BC) (local invasive and/or metastatic) is not curable even with cytotoxic chemotherapy, immune checkpoint inhibitors, and targeted treatment. Targeting GSK-3β is a promising novel approach in advanced BC. The induction of autophagy is a mechanism of secondary resistance to various anticancer treatments. Our objectives are to investigate the synergistic effects of GSK-3β in combination with autophagy inhibitors to evade GSK-3β drug resistance. Small molecule GSK-3β inhibitors and GSK-3β knockdown using siRNA promote the expression of autophagy-related proteins. We further investigated that GSK-3β inhibition induced the nucleus translocation of transcription factor EB (TFEB). Compared to the GSK-3β inhibition alone, its combination with chloroquine (an autophagy inhibitor) significantly reduced BC cell growth. These results suggest that targeting autophagy potentiates GSK-3β inhibition-induced apoptosis and retarded proliferation in BC cells.

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Section: Discussionmentioning

confidence: 99%

Targeting Pro-Survival Autophagy Enhanced GSK-3β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells

et al. 2023

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“…In our previous works [10,24,42], we provided a local analysis of the stability of the equilibrium states of the model only in simulation ways, because the model consists of 10 equations, which made the analytical analysis of stationary points very difficult. Using the general method of Lyapunov functionals construction [15,16] and the method of linear matrix inequalities (LMIs) [17][18][19][20] gives a possibility for research of the "big" system's stability.…”

Section: Discussionmentioning

confidence: 99%

Stability Analysis of Delayed Tumor-Antigen-ActivatedImmune Response in Combined BCG and IL-2Immunotherapy of Bladder Cancer

Bunimovich‐Mendrazitsky¹,

Shaikhet²

2020

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We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The main goal of this research is to predict the outcome of BCG + IL-2 treatment combinations. We examined whether the delay effect caused by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells after BCG and IL-2 immunotherapy influences success in bladder cancer treatment. To do this, we introduce a system of differential equations where the variables are the main participants in the immune response after BCG installations to fight cancer: the number of tumor cells, BCG cells, immune cells, and cytokines involved in the tumor-immune response. The relevant parameters describing the dynamics of the system are taken from a variety of biological, clinical literature and estimated using the mathematical models. We examine the local stability analysis of non-negative equilibrium states of the model. In theory, treatment could improve system stability, and we analyze the stability of all equilibria using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs). Our results prove that the period for the proliferation of tumor antigen-specific effector cells does not influence to the success of the non-responsive patients after an intensified combined BCG + IL-2 treatment.

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“…The dosage of the vaccine is a constant dose (Nave et al, 2019). In the first step of the study, rats from group 1 and group 2 were injected intramuscularly and intraperitoneally, respectively, with 0.5 mL 1  10 6 CFU/mL of formalin-killed M. haemolytica-exopolysaccharide adjuvant.…”

Section: Vaccination Experimental Designmentioning

confidence: 99%

Attempts to Stimulate Immunology Responses by Intramuscular and Intraperitoneal Delivery of EPS-Adjuvanted Mannheimiosis Vaccine

Mansour¹,

Razzak²,

Sheikh³

et al. 2022

American Journal of Animal and Veterinary Sciences

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This study was conducted on 48 male Sprague Dawley rats to determine the immunological responses of experimental adjuvanted vaccines of Mannheimia haemolytica A2 (M. haemolytica A2) injection and to observe their protection level upon live M. haemolytica A2 challenge. Fortyeight clinically healthy Sprague Dawley rats were divided into four groups; Groups 1 and 2 were vaccinated intramuscularly and intraperitoneally, respectively, with an Exo-Polysaccharide (EPS)-adjuvanted vaccine prepared from formalin-killed M. haemolytica serotypes A2, Group 3 with formalin killed M. haemolytica seed. At the same time, Group 4 received intraperitoneally Phosphate Buffer Saline (PBS) as a control. After the first vaccination dose, Groups 1,2, and 3 showed a gradual increase in IgM, IgG, and IgA levels significantly (p<0.05). However, their level started to decline six weeks post-vaccination, indicating that the booster dose was needed. Upon the delivery of the second booster dose, antibodies titer showed a persistent increase significantly (p<0.05), especially the serum IgG level. All groups were challenged with live virulent Mannheimia haemolytica A2 after the level of antibodies declined twice after the second booster was delivered. No rat deaths were found in the Combined EPS -M. haemolytica adjuvant vaccine after 14 days following the challenge (0%). In unvaccinated rats, higher mortality and morbidity were noted (100%) and less was reported in rats receiving M. haemolytica A2 Vaccine seed (8%). Histologically at two weeks, post-challenge revealed negligible lung lesions in groups 1 and 2 and mild lesions in group 3. Lung lesions were recorded in all unvaccinated control rats. Furthermore, M. haemolytica A2 re-isolated successfully from lung samples in groups 3 and 4. In conclusion, Rats receiving adjuvant-M. haemolytica vaccine confers reasonably high preventive efficacy compared to M. haemolytica A2 by itself. Further studies should be conducted on measuring the antibody titer in different vivo, such as goats or sheep.

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<em>BCG</em> and <em>IL</em> − 2 model for bladder cancer treatment with fast and slow dynamics based on <em>SPVF</em> method—stability analysis

Cited by 17 publications

References 30 publications

Targeting Pro-Survival Autophagy Enhanced GSK-3β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells

Targeting Pro-Survival Autophagy Enhanced GSK-3β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells

Stability Analysis of Delayed Tumor-Antigen-ActivatedImmune Response in Combined BCG and IL-2Immunotherapy of Bladder Cancer

Attempts to Stimulate Immunology Responses by Intramuscular and Intraperitoneal Delivery of EPS-Adjuvanted Mannheimiosis Vaccine

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