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Published on: May 27, 2015
Morphological features of doxorubicin-resistant Walker 256 carcinosarcoma and response of mast cells
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Background:
The mechanisms of drug resistance of cancer have not been yet elucidated in details. Recently, the role of mast cells (MCs) in the development of drug resistance has been brought in the limelight. The aim of the study was to examine the morphological features of doxorubicin (DOX)-resistant Walker 256 carcinosarcoma and to assess the response of MCs and histamine content in these cells in relation to the development of resistance to DOX as well as in DOX-resistant tumors.
Materials And Methods:
The DOX resistance was induced by serial passages of Walker 256 carcinosarcoma in rats in the setting of DOX treatment in vivo. MCs in tumors were detected in the sections by staining with Toluidine Blue O. Histamine content in MCs stained with solution of Water Blue-Orcein was assessed by Astaldi semiquantitative method taking into account different staining intensity.
Results:
Formation of DOX resistance in the course of serial passages of Walker 256 carcinosarcoma was accompanied by the increase in the number of MCs in tumors and histamine content. Nevertheless, in tumors with phenotype of complete DOX resistance the number of histamine-containing MCs decreased to the same level as in tumors of the original strain that are DOX-sensitive.
Conclusion:
MCs are involved in formation of DOX resistance in Walker 256 carcinosarcoma.
Insights
Mast cells (MCs) play a role in doxorubicin (DOX) resistance development in Walker 256 carcinosarcoma. Their numbers and histamine content initially increase with DOX resistance but decrease in fully resistant tumors.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Mechanisms of cancer drug resistance remain incompletely understood.
- Mast cells (MCs) are increasingly recognized for their role in drug resistance.
- Doxorubicin (DOX) resistance in cancer is a significant clinical challenge.
Purpose of the Study:
- To investigate the morphological characteristics of doxorubicin (DOX)-resistant Walker 256 carcinosarcoma.
- To evaluate the response of mast cells (MCs) and their histamine content in relation to DOX resistance.
- To analyze MCs and histamine levels in both developing and established DOX-resistant tumors.
Main Methods:
- DOX resistance was induced in Walker 256 carcinosarcoma via serial in vivo passages with DOX treatment.
- Mast cells (MCs) in tumor sections were identified using Toluidine Blue O staining.
- Histamine content in MCs was quantified using the Astaldi semiquantitative method with Water Blue-Orcein staining.
Main Results:
- Increased numbers of mast cells (MCs) and elevated histamine content were observed during the development of DOX resistance.
- In tumors exhibiting complete DOX resistance, the count of histamine-containing MCs returned to levels similar to DOX-sensitive tumors.
- These findings suggest a dynamic role for MCs in the progression of DOX resistance.
Conclusions:
- Mast cells (MCs) are implicated in the development of doxorubicin (DOX) resistance in Walker 256 carcinosarcoma.
- The observed changes in MCs and histamine content highlight their potential as modulators of drug resistance.
- Further research is warranted to elucidate the precise mechanisms by which MCs influence DOX resistance.
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