Vivekanand Gupta

Sex dimorphism in antitumor response of chemotherapeutic drug cisplatin in a murine host-bearing a T-cell lymphoma.

Previously we have demonstrated that in-vivo growth of a murine T-cell lymphoma of spontaneous origin designated as Daltons lymphoma (DL) shows sex dimorphism (J Rep Immunol 2005; 65:17–32). It remained unclear, however, if DL growth in female and male tumor-bearing hosts also shows a sex-dependent differential susceptibility to the antitumor action of cancer chemotherapeutic drugs. In this study we have demonstrated that in-vivo administration of anticancer drugs: cisplatin or doxorubicin to the DL-bearing host results in a sex-dependent different antitumor activity of the drugs, causing a sex dimorphism in the antitumor response of the drugs with respect to tumor growth inhibition. The antitumor effect of both drugs was found to be better in male tumor-bearing hosts compared with female tumor-bearing hosts. The study also shows that DL cells obtained from male and female tumor-bearing hosts display a differential growth response to following treatment with cisplatin in vitro. Cell growth regulatory proteins: interleukin-2, interferon-&ggr;, tumor growth factor-&bgr;, p53, caspase-activated DNase, vascular endothelial growth factor, and interleukin-2 receptor were found to be involved in the observed sex-specific response of DL cells to the antitumor action of cisplatin. Moreover, gonadal hormones: androgen, estrogen, and their specific antagonists flutamide and tamoxifen were found to directly modulate the cytotoxicity of cisplatin against DL cells in vitro. This study, therefore, suggests for the first time that the efficacy of cancer chemotherapeutic may vary in a sex-specific manner in a host-bearing a T-cell lymphoma.

ORIGINAL ARTICLE: Gender Dimorphism of Macrophage Response to GMCSF and IL‐4 for Differentiation into Dendritic Cells

Problem  We previously demonstrated the existence of gender dimorphism in a murine tumor model with respect to the growth of a spontaneous T‐cell lymphoma designated as Dalton’s lymphoma and several aspects of host‐tumor interaction. We also demonstrated the involvement of macrophages in manifestation of gender‐dependent differential tumor growth [ J Reprod Immunol 2005; 65:17, Cancer Invest 2006; 24:1, J Biomed Sci 2007 (in press), J Reprod Immunol 2007; 74:90 ]. Although monocytes/macrophages of tumor‐bearing hosts have been used to differentiate into macrophage‐derived dendritic cells for various applications in the immunotherapy of cancer, it remains unclear if macrophages show a gender‐dependent differential response to the signals of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) for differentiation to cells with dendritic cell morphology (MO‐DC) and if these MO‐DC have a gender‐dependent differential therapeutic efficacy in inhibiting tumor growth.

Effect of intrauterine exposure of murine fetus to cyclophosphamide on development of thymus.

The objective of this study was to demonstrate thymic alterations produced by cyclophosphamide intervention during intrauterine life of murine fetus. Cyclophosphamide (CP) was administered to pregnant mice on day 11 of gestation in a single dose of 10 mg/kg body weight. Fetuses were dissected out on day 19 and studied for various effects on thymus. Thymus of fetuses exposed to cyclophosphamide showed thymic atrophy with retardation of thymic size and a remarkable shrinkage in lobular morphology. Histological studies showed a massive depletion of thymic cortex. Study of thymocytes revealed an increase in apoptotic cell count and percent DNA fragmentation along with a decrease in proliferation. Thymocytes obtained from fetuses of CP-treated mice showed a higher expression of caspase-activated DNase (CAD) indicating that the CP-dependent induction of apoptosis in thymocytes involved caspase pathway. The results of the present study may help in understanding the mechanism of the teratogenic effect of cyclophosphamide on thymus.

Effect of Neem (Azadirachta indica) oil on the progressive growth of a spontaneous T cell lymphoma

SUMMARY The present study was undertaken to investigate the effect of in vivo administration of neem oilintra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphomaof spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice wereadministered various doses of neem oil mixed in groundnut oil, which was used as a dilutingvehicle or for administration to control DL-bearing mice. Administration of neem oil resulted inan acceleration of tumor growth along with a reduction in the survival time of the tumor-bearinghost. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes,bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oilinstead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression alongwith a collapse of the host’s anti-tumor machinery. These observations will thus have long lastingclinical significance, suggesting caution in use of neem oil for treatment of cancer.Key words: Neem oil; Tumor growth; Tumor-associated macrophages

ORIGINAL ARTICLE: Gender Dimorphism of Macrophage Response to GMCSF and IL-4 for Differentiation into Dendritic Cells: GENDER DIMORPHISM OF MACROPHAGE RESPONSE

Problem  We previously demonstrated the existence of gender dimorphism in a murine tumor model with respect to the growth of a spontaneous T‐cell lymphoma designated as Dalton’s lymphoma and several aspects of host‐tumor interaction. We also demonstrated the involvement of macrophages in manifestation of gender‐dependent differential tumor growth [ J Reprod Immunol 2005; 65:17, Cancer Invest 2006; 24:1, J Biomed Sci 2007 (in press), J Reprod Immunol 2007; 74:90 ]. Although monocytes/macrophages of tumor‐bearing hosts have been used to differentiate into macrophage‐derived dendritic cells for various applications in the immunotherapy of cancer, it remains unclear if macrophages show a gender‐dependent differential response to the signals of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) for differentiation to cells with dendritic cell morphology (MO‐DC) and if these MO‐DC have a gender‐dependent differential therapeutic efficacy in inhibiting tumor growth.