Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach

Law, S.K. Alex; Maiti, Debasish; Palit, Aparna; Majumder, Durjoy; Basu, Kaustuv; Chaudhuri, Swapna; Chaudhuri, Surabhi

doi:10.1016/s0165-2478(00)00317-5

Cited by 25 publications

(25 citation statements)

References 15 publications

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“…Leukemia control mice are produced by challenging in intraperitoneally injected with ENU at 80 mg/Kg body weight at -3 weeks old condition twice in one week interval [15,16].…”

Section: Treatment and Maintenance Of Animalsmentioning

confidence: 99%

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

Singha¹,

Bhattacharjee²,

Maiti³

2015

Int Jour of Biomed Res

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Objectives: Murine macrophages were playing a key role against microbes and foreign particles as well as help in solid tumorigenesis in the host body. In this experiment we were trying to evaluate the protein tyrosine kinase (PTK) activity in macrophages from experimentally induced leukemic animal model. Methods: Balb/C mice were divided into four groups, two groups were challenged with N-N' ethyl nitrosourea (ENU) and two groups remained without ENU challenged condition. After confirmation of leukemia induction, one normal and one ENU challenged groups were received rmIL-3 and rmGM-CSF in combination for 4 consecutive days. Disease was confirmed by histological studies of peripheral blood and bone marrow smear. PTK activity assay were done using universal tyrosine kinase assay kit. Results: Protein tyrosine kinase (PTK) activity of macrophages was increased in leukemic animal significantly which were reduced after combination of IL-3 and GM-CSF treatment. IFN-γ level in blood serum was increased in leukemic mice and reinstates after treatment. Conclusion: Results suggest that, in leukemia reduced macrophage number can be increased by IL-3 and GM-CSF administration in combination but PTK activity is not involved to increase the number of macrophages. PTK activity may be involved in macrophage activation process in leukemic animal.

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“…Leukemia control mice are produced by challenging in intraperitoneally injected with ENU at 80 mg/Kg body weight at -3 weeks old condition twice in one week interval [15,16].…”

Section: Treatment and Maintenance Of Animalsmentioning

confidence: 99%

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

Singha¹,

Bhattacharjee²,

Maiti³

2015

Int Jour of Biomed Res

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“…Similarly bone marrow from normal, leukemic and BRM treated animals was isolated and maintained as single cell suspension in an aseptic condition. The cells were subjected to centrifugation at 1000 rpm for 20 min on a bi-layered percoll density gradient namely 1.077 at the bottom and 1.050 at the top (Law et al, 2001). Cells obtained from top (i.e low density compartment or LDC) and bottom (i.e high density compartment or HDC) layers were collected separately and washed thrice in PBS followed by culturing in RPMI media.…”

Section: Blood Hemogrammentioning

confidence: 99%

“…Bone marrow derived LDC and HDC cells of all groups were taken from 48-hour cultures (4 wells pooled together) and were subjected to flowcytometric analysis for the presence of stem cells (Law et al, 2001). Percentage of CD34 + population in LDC and HDC cells were scanned using FITC conjugated antibody against CD34 + (BD Biosciences, USA).…”

Section: Flow Cytometrymentioning

confidence: 99%

“…The functional efficacy of the cells isolated as above has been carried on in each group as follows, cytotoxicity assay: Cytotoxic efficacy by fluorochrome (HO-33342) release assay (Law et al, 2001). This consists of lysing the HO-33342 labelled target tumor cells (Dalton's lymphoma) by effector bone marrow cells (LDC and HDC) at a ratio of 10:1 (T: E) and measuring the fluorochrome released in the supernatant following 18 hr of incubation at 37 0 C and 5% CO 2 atmosphere.…”

Section: Studies On Cell Mediated Immune Parametersmentioning

confidence: 99%

“…In-vivo functional assays from normal and leukemic hematopoiesis have been studied to identify the cytokines; chemokines and adhesion molecules which regulate the development of normal and leukemic stem cells (Meydan et al, 1996;Nagasawa et al, 1996).The immune physiology of stem and stroma in normal and leukemic condition however remain largely unexplored although the defence within the bone marrow cavity is found to remain intact. Several reports using growth factors and BRMs are now taking over for stem cell manipulation and subsequent application for immunotherapy (Law et al, 2001).The functional capability of such cells would however, be considered to be an important factor before cytotherapeutic approaches are made in this aspect. The present work attempted to explore the intimate structure function correlationship between the stem and the stromal cells at the ultrastructural level of in-vitro system, in-vivo leukemic experimental model, and that following application of non-specific BRMs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biological Response Modifiers Influence Structure Function Relationship of Hematopoietic Stem and Stromal Cells in a Mouse Model of Leukemia

Basu

Mukherjee²,

Law³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Biological response modifiers (BRMs) can alter interactions between the immune system and cancer cells to boost, direct, or restore the body's ability to fight disease. Mice with ethylnitrosourea-(ENU) induced leukemia were here used to monitor the therapeutic efficacy of lipopolysaccaride (LPS), Bacillus Calmette Guerin (BCG) and sheep erythrocytes (SRBC). Flow cytometry based CD34+ positivity analysis, clonogenicity, proliferation and ultrastructure studies using scanning electron microscopy (SEM) of stem cells in ENU induced animals with and without BRMs treatment were performed. BRMs improved the stem-stromal relationship structurally and functionally and might have potential for use as an adjunct in human stem cell therapy.

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A review of the mutagenic potential of N‐ethyl‐N‐nitrosourea (ENU) to induce hematological malignancies

Nath

Maiti

2022

J Biochem & Molecular Tox

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This review is intended to summarize the existing literature on the mutagenicity of N-ethyl-N-nitrosourea (ENU) in inducing hematological malignancies, including acute myeloid leukemia (AML) in mice. Blood or hematological malignancies are the most common malignant disorders seen in people of all age groups. Driven by a number of genetic alterations, leukemia rule out the normal proliferation and differentiation of hematopoietic stem cells (HSCs) and their progenitors in the bone marrow (BM) and severely affects blood functions. Out of all hematological malignancies, AML is the most aggressive type, with a high incidence and mortality rate. AML is found as either de novo or secondary therapeutic AML (t-AML). t-AML is a serious adverse consequence of alkylator chemotherapy to the cancer patient and alone constitutes about 10%−20% of all reported AML cases. Cancer patients who received alkylator chemotherapy are at an elevated risk of developing t-AML. ENU has a long history of use as a potent carcinogen that induces blood malignancies in mice and rats that are pathologically similar to human AML and t-AML. ENU, once entered into the body, circulates all over the body tissues and reaches BM. It creates an overall state of suppression within the BM by damaging the marrow cells, alkylating the DNA, and forming DNA adducts within the early and late hematopoietic stem and progenitor cells. The BM holds a weak DNA repair mechanism due to low alkyltransferase, and poly [ADP-ribose] polymerase (PARP) enzyme content often fails to obliterate those adducts, acting as a catalyst to bring genetic abnormalities, including point gene mutations as well as chromosomal alterations, for example, translocation and inversion. Taking advantage of ENU-induced immune-suppressed state and weak immune surveillance, these mutations remain viable and slowly give rise to transformed HSCs. This review also highlights the carcinogenic nature of ENU and the complex relation between the ENU's overall toxicity in the induction of hematological malignancies.

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Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach

Cited by 25 publications

References 15 publications

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

Biological Response Modifiers Influence Structure Function Relationship of Hematopoietic Stem and Stromal Cells in a Mouse Model of Leukemia

A review of the mutagenic potential of N‐ethyl‐N‐nitrosourea (ENU) to induce hematological malignancies

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