Immune response of mice exposed to cis-diamminedichloroplatinum

Bagasra, Omar; Currao, L; DeSouza, Luis R.; Oosterhuis, J. Wolter; Damjanov, Ivan

doi:10.1007/bf00199723

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…Cisplatin is known to increase a number of immune-related activities. Mice treated with cisplatin mount an enhanced splenic plaque-forming cell response to sheep erythrocytes and pneumococcal polysaccharide in vitro [2] and an enhanced responsiveness to tumor cells in vivo [14,26] as well as in vitro [26]. In addition to its effect on immune activity, cisplatin has also been shown to stimulate spontaneous human monocyte-mediated cytotoxicity directly [14].…”

Section: Discussionmentioning

confidence: 96%

“…Regardless of the type of effector cells that mediate lysis, the results presented demonstrate that naturally occurring cytotoxic cells of the host have the potential to increase the rate or level of killing of tumor cells in the presence of cisplatin. These cells along with other host responses, which are known to be increased in the presence of cisplatin [2,14,26], may contribute to the overall anticancer effect of cisplatin.…”

Section: Discussionmentioning

confidence: 97%

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The anticancer drug, cisplatin, increases the naturally occurring cell-mediated lysis of tumor cells

Collins

Kao

1989

Cancer Immunol Immunother

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It has been proposed that a component of the antitumor potential of the chemotherapeutic agent, cisplatin, resides in the host's ability to respond to cisplatin-treated tumor cells. Here we report that tumor cells that are normally resistant to lysis mediated by naturally occurring cytotoxic cells showed an increased sensitivity to lysis mediated by murine spleen cells or human peripheral blood monocytes and lymphocytes when cisplatin was added at the beginning of the lytic assay. This was shown for the lysis of both murine and human tumor cells. The pretreatment of tumor cells, but not effector cells with cisplatin caused an increase in lysis in the presence of murine spleen cells or human peripheral blood leukocytes, indicating that the effect of cisplatin is to reduce resistance to lysis by these effector cells. The lysis of tumor cells by naturally occurring cytotoxic cells was blocked by antibodies specific for tumor necrosis factor. In addition, the ability of cisplatin to increase lysis was seen with cells that are sensitive to natural cytotoxic cells, but not with cells that are sensitive to natural killer cells. These results suggest that the effector cells that mediate the lysis of these tumor cells in the presence of cisplatin are likely to be natural cytotoxic cells. The ability of cisplatin to increase the lysis of tumor cells by naturally occurring cytotoxic cells indicates that these cells may be a host defense mechanism that contributes to the anticancer potential of cisplatin.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

The anticancer drug, cisplatin, increases the naturally occurring cell-mediated lysis of tumor cells

Collins

Kao

1989

Cancer Immunol Immunother

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“…High (12 mg/kg) and low (2 mg/ kg) doses of cisplatin were used in a previous study, 17 but the high dose (12 mg/kg) proved to be fatal in some mice. Therefore we used a nonfatal dose (10 mg/kg cisplatin) for the HB group.…”

Section: Discussionmentioning

confidence: 98%

Induction of natural killer suppressive factor in murine peritoneal cavity by intraperitoneal bolus administration of high-dose cisplatin

Ishikawa

Shimoda

Shiraishi

et al. 2000

International Journal of Clinical Oncology

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Background. Intraperitoneal (i.p.) chemotherapy is frequently utilized in patients with advanced gastric cancer or peritoneal dissemination. We investigated whether i.p. administration of cisplatin at high or low doses would impair host local immunity with respect to the induction of natural killer (NK) cell suppressive factor in the murine peritoneal cavity. Methods. Cisplatin was administered at a total dose of 10 mg/kg according to two schedules: high-dose bolus injection (HB; 10 mg/kg) and low-dose consecutive injections (LC; 2 mg/kg daily for 5 days). The supernatant obtained from the peritoneal lavage fluid was added during normal splenocyte-mediated NK cytotoxicity assay. The phenotypes of peritoneal exudate cells were analyzed using anti-F4/80 monoclonal antibody (MAb) and anti-I-A MAb. Results. NK cell activity was significantly inhibited by the supernatant obtained from the HB group 7 days after the administration of cisplatin (40.6% of NK cell activity in controls; P < 0.05). This inhibition was partly restored by prostaglandin E(2) (PGE(2)) antiserum (69.5% of NK cell activity in controls). NK cell activity was not inhibited at any point by exposure to the supernatant of the LC group. I-A(-) peritoneal macrophages were more abundant in the HB group than in the LC group (2.9 x 10(6) vs 4.6 x 10(5) on day 3; P < 0.05). Conclusion. These results suggest that intraperitoneal bolus administration of high-dose cisplatin induces NK suppressive factors, including PGE(2), in the peritoneal cavity, whereas low-dose consecutive administration does not.

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“…indiscriminate elimination of both T and B lymphocytes, depression of NK cell activity and deterioration of monocyte function [2,9,20]. One possible mechanism is an impairment of the host immune system resulting in immunosuppression of antitumor resis.tance, e.g.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice

Kanclerz

Chapman

1987

Clin Exp Metast

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Both B16 melanoma and Lewis lung carcinoma growing in C57/Bl mice spontaneously metastasize to the lungs and other organs. When the tumors are grown in the mouse tail to a specific volume and amputated, the spontaneously disseminated tumor cells can then be independently treated. The effects of a single dose of cyclophosphamide (200 mg/kg), cis-platinum (6 mg/kg) and melphalan (10 mg/kg) on the appearance of pulmonary and other metastases were measured. The cis-platinum treatment was shown to reduce the number and incidence of metastases of both tumors at various times after treatment. The antimetastatic effectiveness of cis-platinum against these two tumors was increased when 2.4 mg/kg was administered each day for five consecutive days after amputation of the primary. Cyclophosphamide, when administered at two-thirds maximum tolerated dose, had a small promoting effect on the number and incidence of pulmonary metastases of Lewis lung carcinoma, whereas, applied in the same dose, it had efficacy in the treatment of disseminated B16 melanoma and inhibited appearance of both pulmonary and lymph-node metastases. When melphalan was administered in single- and multiple-dose regimens, the number and incidence of metastases of both tumors increased at various times after primary tumor amputation. These data suggest that melphalan can promote the growth of disseminated tumor cells in both the lungs and other sites and that some systemic chemotherapies may result in promotion instead of suppression of metastatic disease.

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Immune response of mice exposed to cis-diamminedichloroplatinum

Cited by 10 publications

References 23 publications

The anticancer drug, cisplatin, increases the naturally occurring cell-mediated lysis of tumor cells

The anticancer drug, cisplatin, increases the naturally occurring cell-mediated lysis of tumor cells

Induction of natural killer suppressive factor in murine peritoneal cavity by intraperitoneal bolus administration of high-dose cisplatin

The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice

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