Prevention and synergistic control of Ph+ ALL by a DNA vaccine and 6-mercaptopurine

Köchling, Joachim; Rott, Yvonne; Arndt, Stefanie; Marschke, Christina; Schmidt, Manuel; Wittig, Burghardt; Kalies, Kathrin; Westermann, Jürgen; Henze, Günter

doi:10.1016/j.vaccine.2012.07.037

Cited by 8 publications

(7 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, treatment with the DNA vaccine and berry extract resulted in a decreased leukaemia progression and a significantly longer leukaemia-free and overall survival compared with mice treated with the DNA vaccine alone, and 90% of mice survived. Although berry extract in contrast to 6-MP did not induce caspases in BM185 cells in vitro, the treatment efficacy of DNA vaccination and berry extract was comparable with the efficacy of DNA vaccination and 6-MP in vivo as reported previously (12). Because berry extract alone has been shown to be not effective and because the DNA vaccination was the most effective strategy to treat minimal residual disease, we suggest that the synergism of berry extract with the DNA vaccine is based on an enhanced antileukaemia immune response.…”

Section: Discussionsupporting

confidence: 85%

“…The mechanisms by which the immune system responds to foreign antigens due to infection or malignant degeneration depend on complex interactions between the innate and adaptive immunity (49). We demonstrated previously that DNA vaccination induces innate and adaptive immune reactions by activation of CD4 + T cells, CD8 + T cells and NK cells, all of which contribute to the antileukaemia immune response (12).…”

Section: Discussionmentioning

confidence: 99%

“…As immune suppression is associated with an increased risk of relapse , immune therapy may lead to long‐lasting remission. We have shown previously that specifically designed DNA vaccines not only prevent leukaemia in immunised mice but also induce elimination of pre‐existing leukaemia cells and that the vaccine acts synergistically with 6‐MP . In general, the current maintenance therapy with 6‐MP and methotrexate is effective and well tolerated by most patients.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Köchling¹,

Schmidt

Rott

et al. 2013

European J of Haematology

Self Cite

View full text Add to dashboard Cite

Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph(+) ALL) still remains poor. Because most adults eventually relapse without allogeneic stem cell transplantation, which is not available for all patients, novel strategies are required for relapse prevention. As the integrity of the immune system is essential for the control of remaining leukaemia cells, we compared the efficacy of anthocyanins, imatinib and a DNA-based vaccine as non-immunosuppressant components with 6-mercaptopurine (6-MP) to control minimal residual disease in vitro and in vivo using different leukaemia cell lines and syngeneic mice. Proliferation of Ph(+) ALL was significantly better inhibited by anthocyanin-rich berry extract or imatinib compared with 6-MP. Although anthocyanins induced apoptosis in some leukaemia cell lines, the level of caspase-3, caspase-8 and caspase-9 was significantly lower compared with imatinib and 6-MP. When used as single components, anthocyanins and imatinib mesylate failed to eradicate pre-existing Ph(+) ALL in syngeneic mice, while 6-MP led to 10% and DNA vaccination to 56% survival. Intriguingly, only the combination of DNA vaccination with berry extract but not with the isolated anthocyanin, cyanidin-3-rutinoside or imatinib further increased leukaemia-free and overall survival, and 90% of lethally challenged mice survived. We suggest that induction and enhancement of a leukaemia-specific immunity by DNA vaccination and anthocyanin-rich berry extract can also decrease the relapse rate in patients with Ph(+) ALL. Furthermore, this approach may serve as strategy for maintenance therapy of other malignancies.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Köchling¹,

Schmidt

Rott

et al. 2013

European J of Haematology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite the variety of structural characteristics, most HDACs inhibitors, including hydroxamates, can be considered to have a common pharmacophore, which mainly contains three parts: a zinc ion binding group (ZBG) and a cap group which makes contacts with the amino acid residues on the rim of the enzymatic active site, joined by a linker domain with proper length. 18,19) Many purine compounds have been described as anticancer derivatives, such as early 6-mercaptopurine have been extensively used in clinical as an anti-tumor drug through inhibiting the synthesis of nucleic acid in tumor cells, 20,21) and then Nelarabine, Fludarabine, Cladribine, Clofarabine were discovered as anti-tumor drugs. [22][23][24][25] Substituted at 2, 6, 8 and 9 positions have been the focus of structural modifications of the purine ring.…”

mentioning

confidence: 99%

Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors

Yang

Mai

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, the most promising compound was 7m'. Western blot analysis indicated the compounds 7f', 7l', 7m', 7o' could increase histone H3 acetylation levels in HCT116 and K562 cell lines, and 7m' increased the level of acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid (SAHA). Molecular docking study revealed that the conformation of 7m' in the active site of HDAC2 was similar to positive drug SAHA, which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.

show abstract

“…MP essential at very low doses become toxic at high doses: chromium, manganese, iron, cobalt, copper and zinc. [11] Metals toxic anyway (MT) include: beryllium, aluminum, antimony, thallium, tin, uranium, tungsten, nickel, arsenic, cadmium, mercury, lead, uranium, gadolinium. [12] Sources Man-made include: electrical installations (Hg, As, Tl), vehicles (Cd), diesel engines (Ni), metallurgical industries and foundries (Pb, As, Cu, Al, Co, Zn, Fe), agriculture (Cu, As , Al, Zn), of waste disposal systems (Hg, Cd, Pb, as) paints (Hg, Cd, Pb), insecticides, rodenticides, fungicides (Hg, as, Cd, Ti), cookware (Al, Cu), wood protection products (As, Cu), disinfectants (Cu, Hg, Ag), vaccines (Hg, Al), dental materials (Hg, Al, Au, Ag, Ni), contrast medium for the resonance nuclear magnetic (Gd).…”

mentioning

confidence: 99%

Toxic metals and autism

Tarro

Renato²,

Franco³

2017

Theory Clin. Pract. Pediatr.

View full text Add to dashboard Cite

Toxic metals (MT) are the major pollution to the land (37.3% in Europe), which are produced mainly by industrial activities, entering a far part of our life cycle, through the skin, breathing, ingestion of foods and water. Especially children in the first three years of life are biologically more vulnerable. The spreading epidemic of Autism and developmental disorders, that has been recorded in industrialized countries during the last 20 years is a sensitive thermometer of the pollution. Tests were carried out on 20 MT in a group of 73 subjects diagnosed with autism, the mean age of 8 years old. All 73 patients were over threshold for at least one metal. Seven metals (mercury, lead, antimony, tin, arsenic, thallium, cesium) had values over 50% (thirty-seven patients). The 26% (nineteen patients) exceeded the threshold for ten or more metals. Gadolinium 1521.21 exceeds threshold times. Mercury (x 379.95), tin (x 118), lead (x 108): presenting the coefficients more elevated. The average values exceed the threshold a lot: Mercury (x 28.14), Lead (x 10.56), Tin (x 9.98). With age increases the threshold exceeded for a lower number of metals. The analysis shows that gender has no significant difference, possibly results from the reduced number of females (18%). A future comparison research remains. We will explore the detoxification capacity difference between two genders affected by autism.

show abstract

Prevention and synergistic control of Ph+ ALL by a DNA vaccine and 6-mercaptopurine

Cited by 8 publications

References 47 publications

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors

Toxic metals and autism

Contact Info

Product

Resources

About

Prevention and synergistic control of Ph+ ALL by a DNA vaccine and 6-mercaptopurine

Cited by 8 publications

References 47 publications

Can anthocyanins improve maintenance therapy of Ph+ acute lymphoblastic leukaemia?

Can anthocyanins improve maintenance therapy of Ph+ acute lymphoblastic leukaemia?

Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors

Toxic metals and autism

Contact Info

Product

Resources

About

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?