Solid tumor models for the assessment of different treatment modalities: II: Rapid, intermediate, and slow growing transplantable rat hepatomas

Looney, William B.; Mayo, Audrey A.; Kovacs, C. J.; Hopkins, Harold A.; Simon, Richard; Morris, Harold P.

doi:10.1016/0024-3205(76)90214-9

Cited by 16 publications

(5 citation statements)

References 23 publications

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“…Previous studies of this series and other investigations using different solid tumor models in different animal species have all demonstrated the variability of response to different forms of treatment in experimental tumors that have been serially transplanted for many years in inbred hosts (1,8,9). This lack of a uniform response to treatment indicates that conventional methods of analysis such as mean values mask important experimental therapeutic results.…”

Section: Methodsmentioning

confidence: 88%

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

Looney¹,

Trefil²,

Hopkins³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically. The use of different treatment methods such as radiotherapy and chemotherapy, or combined chemotherapy, indicates that further improvement in management of solid tumors may be realized if the temporal relationship between tumor and patient response is better understood. One of the more promising approaches to the improvement of cancer treatment is the optimal sequencing of different therapeutic modalities to produce maximal effects on the tumor with minimal effects on the host. Many of the questions related to solid tumors in man can only be answered at this time by use of solid tumor models in animals. Such well-defined and rapidly analyzable tumor models can yield quantitative information concerning the time sequence of toxicity to therapy and the kinetics of recovery of host and tumor.Previous reports from these studies (1-6) have demonstrated that recovery from the effects of a large dose of 5-fluorouracil (5-FUra) in rats occurs 10-11 days after treatment. The maximal rate of tumor volume change occurs 12 days after 5-FUra (4). It has also been demonstrated that the rate of proliferation in the tumor is at a maximum 11-12 days after 5-FUra (3). Studies on the solid tumor model hepatoma 3924A indicated that neither radiation alone [375-1500 roentgens (0.10-0.38 C/kg)] nor 5-FUra alone (50-250 mg/kg) would control tumor growth. However, these results suggested that radiation in combination with 5-FUra treatment could in principle transform the management of a chemotherapeutically resistant solid tumor from an untreatable situation to a treatable situation by the combined modality treatment every 11 days until the tumor is eradicated (2).The present report describes the effectiveness of a therapeutic strategy for the sequential use of chemotherapy with radiotherapy. In addition, a method has been developed to compare the treatment efficiency of successive courses of treatment so that successive effects can be distinguished from integrated ones.Abbreviations: 5-FUra, 5-fluorouracil; OTE, overall treatment efficiency. * This is paper no. 5 of a series. Paper no. 4 is ref. MATERIALS AND METHODSThe analytic methods developed for the evaluation of the effectiveness of single and combined modality therapy on tumor growth cur...

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Section: Methodsmentioning

confidence: 88%

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

Looney¹,

Trefil²,

Hopkins³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…The growth factor was 066 and the cell loss factor 061 (Looney et al, 1971(Looney et al, , 1973(Looney et al, , 1976b.…”

Section: Materials Amd Methodsmentioning

confidence: 99%

Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil

Looney¹,

Schaffner²,

Trefil³

et al. 1976

Br J Cancer

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Summary.-Neither radiation alone (375 to 1500 rad) nor 5 -fluorouracil (FU) alone (50-250 mg/kg) is sufficient to prevent an increase in the volume of the solid tumour model hepatoma 3924A. However, as little as 750 rad with 100 mg/kg FU can reduce the tumour below the volume at the time of treatment for as long as 14 days. A series of combined FU and radiation doses given every 11 days should then result in successively smaller tumour volumes until the tumour is eradicated.Changes in tumour volume were analysed by two different methods: (1) tumours in each treatment mode were grouped together and the average response to treatment determined, and (2) tumour volume changes in individual tumours were analyzed utilizing the x2 technique, which fits the logarithmic tumour volume change with time to polynomials. This two-directional method of analysis has the advantage of permitting both an overview of the main effects of treatment via the averages, and at the same time a detailed examination of the mechanism by which these effects occur through the analysis of individual responses. The results suggest that, in addition to concentrating on the cellular response immediately after therapy, greater emphasis should be placed on the kinetic changes of the tumour 1-3 weeks after single or multiple modality therapy. These findings demonstrate how the sequencing of single and/or combined treatment modalities may be investigated in order to determine how best to obtain maximum effects of treatment on different types of tumours following recovery of the host from the previous treatment series.

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“…Tumor transplantation in syngeneic rodent systems has been widely used for modeling cancers. 44,45 Initial attempts of tumor transplantation using our cell lines in histocompatible miniature swine led to successful growth in cases where recipients were pretreated with irradiation. However, we have not yet achieved tumor growth without immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Establishment of transplantable porcine tumor cell lines derived from MHC- inbred miniature swine

Cho

Wikiel

et al. 2007

Blood

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The lack of transplantable tumors has limited assessment of graft-versus-tumor effects following hematopoietic cell transplantation in clinically relevant largeanimal models. We describe the derivation and characterization of porcine tumor cell lines with initial efforts of tumor transplantation using immunocompromised mice and highly inbred sublines of Massachusetts General Hospital major histocompatibility complex (

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Solid tumor models for the assessment of different treatment modalities: II: Rapid, intermediate, and slow growing transplantable rat hepatomas

Cited by 16 publications

References 23 publications

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil

Establishment of transplantable porcine tumor cell lines derived from MHC- inbred miniature swine

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