• Journal of Microbiology and Biotechnology
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• v.23 no.9
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• pp.1339-1346
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• 2013

Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (${\gamma}$-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of ${\gamma}$-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, ${\gamma}$-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor ${\alpha}$. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and ${\gamma}$-PGA markedly suppressed tumor growth and metastasis. Notably, ${\gamma}$-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that ${\gamma}$-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.31-36
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• 2006

The aim of this study was to elucidate the mechanism of anemia associated with Dangguibohyel-tang (DBT) in rats. Using cyclophosphamide-induced (30mg/kg BW) anemic rats, changes in weight gain, the levels of red blood cell (RBC), hematocrit (Hct), platelet and hemoglobin (Hgb), serum vitamin B12, ALT(GPT) levels and erythropoietin (EPO) gene expression were monitored, and compared with DBT (1,000mg/kg BW, 14d)-treated and EPO (1,000IU/kg BW, 14d, s.c.)-treated rats. Food efficiency ratio (FER) were 31.6%, in normal group, 28.1% in cyclophosphamide-induced control group, 31.7% in DBT-treated group and 25.1%, in EPO-treated group after 14 days. The levels of red blood cell (RBC), hematocrit (Hct), platelet and hemoglobin (Hgb) of DBT-treated group were significantly higher than those of control. And DBT extract administered group showed dominant effects on the recovery of Hgb level. Serum vitamin B12 and ALT(GPT) levels were significantly increased at DBT-treated groups. EPO gene expression was decreased 91,9% in control group, 79.6% in DBT-treated group and 53.9% in EPO-treated group, respectively. These results suggest that administration of DBT could prevent human patient from chemotherapy derived anemia by improving hematological value and EPO status.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.48-55
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• 2019

Current studies have been reported that fruits such as berries may contain both antioxidant and antitumor polyphenols that may be important in this regard. We investigated the immunostimulatory effect of fermented blueberry (Vaccinium corymbosum L.) on cyclophosphamide-induced immunosuppression in animal model. Rats were administered blueberry yeast fermented powder (BYFP) at doses 30, 100, and 300 mg/kg for 4 weeks after cyclophosphamide (Cy) treatment, respectively. The immunomodulatory effect of BYFP were measured both in vitro and in vivo, and the changes of blood components were also analyzed. We found that BYFP recovered immunosuppression-mediated decreased liver, spleen, and thymus weights as well as up regulation of white blood cell, lymphocyte, and neutrophil in blood. Moreover, BYFP up-regulated IL-2, TNF-${\alpha}$, and IFN-${\gamma}$ pro-inflammatory cytokine production compared to immune suppressed control group, respectively. According to histological studies, BYFP regenerated significantly on Cy-mediated injured spleen at the high doses (BYFP 300) comparison with Cy-treated groups (immunosuppression). Collectively, these findings suggest that BYFP may have the potential as a dietary immunostimulatory agent.

• Journal of Life Science
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• v.25 no.10
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• pp.1156-1163
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• 2015

The present study investigated the immunomodulatory properties of four different medicinal plants in a cyclophosphamide-treated Balb/c mouse model. One of the four plants, Ulmus macrocarpa, showed partial resistance against immune suppression induced by cyclophosphamide. The bark of U. macrocarpa, commonly known as the Chinese elm, has been used as a pharmaceutical material in Korean traditional medicine to treat bacterial inflammation and induce wound healing. In this study, water extract of U. macrocarpa, named DEU-7, was used for its immunomodulating functional activity. DEU-7 increased the weight of the spleen and the number of splenocytes but did not significantly affect the liver, kidney, and thymus in vivo. A splenocyte viability assay confirmed that DEU-7 influenced ex vivo splenocyte survival. DEU-7 also increased the levels of cytokines, such as IL-2 and IL-4, and immunoglobulins, such as IgM, IgG, and IgA. These results indicated that DEU-7 is involved in the activation of T and B lymphocytes. In addition, DEU-7 was able to maintain the production of cytokines, such as TNF-α, IL-12, and IFN-γ, in the condition of cyclophosphamide-induced immune suppression, suggesting that DEU-7 activated innate immune cells, even under immune suppression. We concluded that DEU-7 aids immunological homeostasis, thereby preventing immune suppression, and aids both innate and adaptive immune response by maintaining the levels of various cytokines and immunoglobulins. Consequently, it is worth investigating the potential of DEU-7 as a supplemental source for immune-enhancing agents.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.60-61
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• 2003

Effects of repeated treatment with butylated hydroxyanisole (BRA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BRA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and subcutaneously challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined.(omitted)

• Journal of Society of Preventive Korean Medicine
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• v.10 no.1
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• pp.13-32
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• 2006

In order to indentify the effect of Astragali Radix(A.R) on cyclophosphamide(C.Y) induced leukopenia, A.R. extracts(EAR) were treated to mice orally, and blood sampling was done by periods. For the in vivo experiments, mice were divided into 4 groups, which treated EAR before, or after C.Y injection, or both, or none. Rapid normalization in the peripheral blood count of WBC, neutrophils, lymphocytes, RBC, and platelets observed in every EAR treated group regardless of the treatment periods of EAR. These studies suggest that, A.R. premedication can be effective in protection of bone marrow suppression during anticancer therapy.

• Korean Journal of Pharmacognosy
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• v.31 no.3
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• pp.325-334
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• 2000

Rhizoma Rehmanniae Preparata is a Chinese herbal tonic. The hemopoietic effects of Rhizoma Rehmanniae Preparata(4-time steamed Jihwang, 4-time steamed double dose Jihwang, 8-time steamed Jihwang, 8-time steamed double dose Jihwang) were examined using in vitro rat(SD) model. Cyclophosphamide(150 mg/kg) was injected into experimental groups and control group to induce bone marrow suppression. Oral administration of Rhizoma Rehmanniae Preparata suppressed hormone levels of $T_4\;and\;T_3$. Reticulocyte count was increased by the bone marrow suppression.

• Korean Journal of Veterinary Research
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• v.38 no.1
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• pp.119-128
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• 1998

This study was performed to investigate the pathogenesis of hepatic granuloma and hepatic fibrosis induced in mice infected with Capillaria(C) hepatica and treated cyclophosphamide. The results were as grossly well-defined yellowish white spots and small nodules at the surface of the liver were scattered. Histopathologically, there were numerous granulomas composed of eggs and fragments of C hepatica surrounded by heavy infiltration of inflammatory cells. Severe fibrosis was observed around granulomas. Pathological lesions of group infected with C. hepatica and then injected with cyclophosphamide were most severe than those of other groups. Therefore this study suggested that hepatic fibrosis induced by C hepatica in mice would be useful for animal model of hepatic fibrosis in human.

• Archives of Pharmacal Research
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• v.22 no.6
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• pp.533-541
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• 1999

Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.

• Korean Journal of Clinical Laboratory Science
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• v.46 no.2
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• pp.75-78
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• 2014

Green tea and tea polyphenols have been studied extensively as cancer chemopreventive agents in recent years. Epigallocatechin-3-gallate (EGCG) is widely recognized as a powerful antioxidant and a free radical scavenger. The purpose of this study was to evaluate the protective effects of green tea catechins (GTC) on the Bleomycin- and Cyclophosphamide-induced cytotoxicity. Cell viability was measured by MTT assay. In the protective effect of GTC, the cell viability was significantly increased by the treatment of GTC. Furthermore, GTC showed the higher protective effect than EGCG and vitamin E. These results suggest that GTC has the protective effect which is related to the prevention of cancer. Our studies show that the continuous presence of EGCG can reduce radical-induced DNA damage in Chinese hamster lung fibroblast cells (CHL cells).