Cyclophosphamide activity against B16 melanoma in a rapid in vitro test system

Hill, George J.; Hill, Helene Z.

doi:10.1002/jso.2930240117

Cited by 4 publications

(14 citation statements)

References 20 publications

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“…We have previously reported that there is a linear relationship between drug dose and prolongation in survival time, indicating that there is an exponential relationship between drug dose and fractional cell kill [15]. Net tumor doubling time is approximately 1.1 days [7]. The EDso in vivo for CY against B16 melanoma is approximately 13 pg/ml [7].…”

Section: In Vivo Experimentsmentioning

confidence: 97%

“…Net tumor doubling time is approximately 1.1 days [7]. The EDso in vivo for CY against B16 melanoma is approximately 13 pg/ml [7].…”

Section: In Vivo Experimentsmentioning

confidence: 99%

“…We have previously reported [7] our studies of the effect of CY activated in vivo, in which plasma from CY injected mice was used in the chemosensitivity assay. Strong inhibitory effect from CY was achieved, reaching a maximum 20 minutes after injection of 20 mg of CY into the activating mouse.…”

Section: Activation Of Cyclophosphamide In Vivomentioning

confidence: 99%

“…B16 tumor cells from S.C. tumors were injected i.p at lo6 cells per mouse into C57BL/6 female mice as previously described [7,13,18,20]. The CY was injected i.p.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

“…The effect of CY on B16 cells was studied in the rapid in vitro test previously described [7]. Briefly, suspensions of tumor cells freshly obtained from C57BL/6 mice were prepared in alpha-MOPS (3-(N-morpholino) propanesulfonic acid) [9] medium with 5 X lo4 or lo5 tumor cells per tube in a total volume of 0.1 ml.…”

Section: Assay Systemmentioning

confidence: 99%

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In vitro activation of cyclophosphamide for an in vitro chemosensitivity assay

Hill

1984

Journal of Surgical Oncology

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The problem of activation of cyclophosphamide (CY) for an in vitro chemosensitivity assay was studied using the B16 melanoma. The efficacy of the S9 hepatic microsomal fraction in vitro was compared with activation by passage of drug in vivo. The effect of CY was assayed by inhibition of tritiated thymidine (3HdThd) uptake by B16 tumor cells in vitro, and by its effect in single dose in vivo on the life span of syngeneic C57BL/6 mice injected with B16 tumor cells. In vivo activation of CY that was achieved by injecting 20 mg of CY intraperitoneally (i.p.) into mice and obtaining plasma 20 minutes later was more rapid and more reproducible, while in vitro activation provided a more potent preparation and a better quantitative correlation with the in vivo effect of CY. The activation activity of different preparations of S9 microsomal fractions was found to be directly related to the activity of aminopyrine demethylase, a mixed function oxidase enzyme, in the S9 fraction, rather than to total protein concentration. The S9-activated drug required 2 1/2 to 3 hours to achieve maximum inhibition of subsequent tumor cell tritiated thymidine (3HdThd) incorporation compared with 20 minutes to achieve maximum inhibition by in vivo activated drug. We conclude that rapid qualitative screening for effectiveness of CY may best be done with in vivo activated drug, whereas quantitative prediction of effective concentration appears to be best achieved with drug activated in vitro by the hepatic S9 fraction.

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Section: In Vivo Experimentsmentioning

confidence: 97%

“…Net tumor doubling time is approximately 1.1 days [7]. The EDso in vivo for CY against B16 melanoma is approximately 13 pg/ml [7].…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Section: Activation Of Cyclophosphamide In Vivomentioning

confidence: 99%

“…B16 tumor cells from S.C. tumors were injected i.p at lo6 cells per mouse into C57BL/6 female mice as previously described [7,13,18,20]. The CY was injected i.p.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Section: Assay Systemmentioning

confidence: 99%

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In vitro activation of cyclophosphamide for an in vitro chemosensitivity assay

Hill

1984

Journal of Surgical Oncology

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Comparative studies of chemotherapy of human tumor cells in vitro by tritiated thymidine uptake inhibition and soft agar clonogenic assay

Zirvi

Hill

1986

Journal of Surgical Oncology

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A rapid nonsterile short-term assay has been investigated in which percent inhibition of incorporation of the DNA precursor (3H)-thymidine is measured following exposure of tumor cells to the test drugs. To evaluate the usefulness of the short-term assay in providing a rapid reliable assessment of chemotherapeutic response, the short-term assay was compared with the soft agar clonogenic assay. Sensitivity to five anticancer drugs was compared using three human tumor cell lines (epidermoid carcinoma of the oral cavity, pancreatic carcinoma, and bladder carcinoma). The short-term assay produced results that were similar to results of the clonogenic assay in two of the three tumors tested, for three drugs (cis-platin, doxorubicin, and BCNU), but did not detect responses to two antimetabolites (5-FU and MTX) in any tumor. Further studies of this short-term assay should focus on alkylating agents and other nonantimetabolites.

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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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Cyclophosphamide activity against B16 melanoma in a rapid in vitro test system

Cited by 4 publications

References 20 publications

In vitro activation of cyclophosphamide for an in vitro chemosensitivity assay

In vitro activation of cyclophosphamide for an in vitro chemosensitivity assay

Comparative studies of chemotherapy of human tumor cells in vitro by tritiated thymidine uptake inhibition and soft agar clonogenic assay

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

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