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At least 19 recordsLinked to original sources
PubMed1975

Solid tumor models for the assessment of different treatment modalities: I. Radiation-induced changes in growth rate characteristics of a solid tumor model.

A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate data from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can be obtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided all of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors.

Animals↗
PubMed1975

The growth characteristics of the metastatic Wistar/Furth Wilms' tumor model.

Growth characteristics, metastatic spread, and survival times were evaluated in a transplantable Wistar/Furth rat Wilms' tumor model. Tumor suspensions of various tumor cell dosages were injected in an attempt to find the optimum level of tumor take. Lung metastases were frequent following tumor injection by all routes. However, tumor spread to the lungs was the least frequent following subcutaneous (SC) injection of the tumor. Survival time for the intramuscular (IM) group was statistically longer at all tumor dose levels. For the 1 X 10(5) tumor dosage, survival time ranged from a mean of 27 days for the intrarenal (IR) group to a mean 42 days for the IM group. For the 1 X 10(4) dosage, survival time ranged from a mean of 37 days for the intraperitoneal (IP) group to a mean of 51 days for the IM group. It is concluded that this animal tumor closely resembles the human Wilms' tumor, and that the point at which the transplanted tumor fails to be successfully transplanted is below the dosage level of 1 X 10(3) tumor cells.

Animals↗
PubMed1978

The multicellular spheroid as a model tumor allograft. II. Characterization of spheroid-infiltrating cytotoxic cells.

Alloimmune lymphoid cells infiltrating multicellular spheroids of EMT6 mammary sarcoma cells (a solid tumor allograft model) have been characterized according to their morphological and functional properties. Both lymphocytes and macrophages were found within spheroids at the time of peak tumor cell damage. Cytotoxic cells specific for allograft antigens were also present. Using a short-term 51-Cr release assay, the cells responsible for cytotoxicity were characterized as a nonadherent, nonphagocytic T cell population. Velocity sedimentation cell separation further demonstrated that these cytotoxic cells had the physical properties of small lymphocytes. Some evidence for selective spheroid infiltration by specifically alloimmune cells was also obtained. The possible relationship of this cellular infiltrate to graft damage is discussed.

Animals↗
PubMed1978

Predictive experimental animal tumor models: a concept.

As an introduction to the session on Animal Tumor Models, a concept of animal model systems in presented that differentiates between models of organ-related diseases such as prostate or bladder cancer and models of a certain class of neoplasms found within a specific organ disease. Thus defined, no one animal tumor can completely represent and be predictive for a disease entity, no more so than can a single clinical experience with prostate cancer, e.g., be representative of all clinical cases. Rather, a block of animal tumors originating from a specific organ that reflects a spectrum of carefully defined growth patterns and reactivities best mimics the overall responses obtained clinically. Because immunotherapy is most logically visualized and applied in an adjuvant mode, its effectiveness as a therapeutic modality is vulnerable to the vagaries of individual tumor response to a primary modality. Therefore, the selection of appropriate tumor models for developmental studies in immunotherapy is critical, and the need for well-defined and characterized test systems in terms of chemotherapy and radiation responsiveness is emphasized.

Animals↗
PubMed1978

Wilms' tumor--model of a curable pediatric malignant solid tumor.

Wilms' tumor is the model of the treatment of a pediatric solid tumor. Initially it appeared that multi-modality therapy, consisting of transabodominal nephrectomy, post-operative radiation therapy to the tumor bed and adjuvant, single agent chemotherapy provided the highest likelihood of disease-free survival. The identification of important prognostic factors, such as histology, tumor weight, lymph node involvement and age at diagnosis has led to a re-examination of the treatment of Wilms' tumor. Future therapeutic developments will include the administration of less therapy to some well defined groups of patients, and the exploration of new programs for patients who have been demonstrated to have a poor prognosis using currently accepted treatment techniques.

Adolescent↗
PubMed1978

[Immunological surveillance mechanism of a rat brain tumor model--study of time-lapse changes in the concomitant immunity of peripheral blood lymphocytes by microcytotoxicity assays (author's transl)].

A rat brain tumor model was prepared by semi-stereotactically implanting 1 x 10(6) RG--C6 tumor cells (chemically induced and maintained in vitro) in the right caudate nucleus of inbred WKA rat by a new method "Soft Agar Technique" which we developed. The tumor grew at a nearly fixed rate. We measured the maximum tumor area and the whole brain area of the rat brain which were sectioned coronary in series. We regarded the percentage of the tumor area to the whole area of the same section as tumor growth index. Microcytotoxicity assays of peripheral blood lymphocytes were performed at various stages of the tumor growth. RG--C6 cells were used as target cells, and they mixed with lymphocytes by Takasugi and Klein's method. Cytotoxicity index was higher in 22 cases (80.00 +/- 16.67; tumor growth index, 0--10) than in 28 cases of the control group (67. 25 +/- 19.68) and then gradually decreased with tumor growth (Fig. 2). At last cytotoxicity index went down to 41.55 +/- 24.94 in 11 cases (tumor growth index, over 31). These observations have a strong resemblance to other animal tumor models and suggest that the rat having brain tumor intra-axially have concomitant immunity especially in the first stage of tumor bearing.

Animals↗
PubMed2025

Advances and challenges in human 3D solid tumor models.

The field of cancer biology and therapeutics has soared in the past several decades with new therapeutic modalities and options for patients, such as chemoradiotherapy, immunotherapy, and combination therapy. This dramatic success in expanding patient options is primarily attributed to the development of various model systems to elucidate drivers of oncogenesis, tumor maturation and evolution, and response to therapeutics. While mouse models have been a workhorse of cancer research, technological progress in ex vivo patient-derived tumor models has afforded more tunable and scrutable systems for patient-predictive platforms and mechanistic study. This review explores the technological innovations in 3D solid tumor models and their applicability to various aspects of cancer biology and identification of therapeutics. Features of the tumor and tumor microenvironment like spatial heterogeneity, multicellular populations and genomic variations are addressed and elaborated through the establishment of new in vitro models. We further address the integration of perfusable vasculature with 3D tumor models and the potentially wide-ranging applications of these more complex platforms in precision medicine and cancer immunotherapy. Finally, we provide an outlook on the future of experimental cancer models for both biological investigation and bench-to-bedside pipeline development.

Journal Article↗
PubMed1978

Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models.

An analysis of dose and schedule dependence of calcium leucovorin rescue during high-dose methotrexate therapy of ascitic forms of l1210 leukemia and Sarcoma 180 is reported. Schedules with very delayed "low-dose" leucovorin rescue following lethal doses of methotrexate were highly effective in preventing toxicity and achieved a pronounced antitumor effect in both ascites tumor models. Best results were obtained on a schedule of methotrexate (400 mg/kg s.c.) followed 16 to 20 hr later by calcium leucovorin (12 mg/kg s.c.) given once every 2 hr for a total of 5 doses. Progressive increases in the calcium leucovorin dosage on any schedule reduced both toxicity and the antitumor effect of methotrexate in each model. Following a single course of therapy, essentially no toxicity was observed, and the antitumor effects were 2-fold (L1210 leukemia) and 4-fold (Sarcoma 180) greater than a single, maximally tolerated dose (24/kg s.c.) methotrexate alone. An increase in the methotrexate dosage to 800 mg/kg s.c. with or without an increase in calcium leucovorin dosages on the same schedule did not appreciably increase the antitumor effect observed. Two courses of high-dose methotrexate (400 mg/kg s.c.) with leucovorin rescue (24 mg/kg s.c. 16, 20, and 24 hr after drug) given with an 8-day interval between courses doubled the total antitumor effect in each model with no substantial increase in toxicity and gave long-term survivors with Sarcoma 180. The results, overall, are in close agreement with prior prediction for schedule and dose dependence made on the basis of related pharmacokinetic and biochemical studies in murine tumor models reported from this laboratory.

Animals↗
PubMed1977

Correlation of animal brain tumor models with human neuro-oncology.

The paper reviews the histopathology and cytopathology of a number of experimental animal brain tumor models to determine their relevance to human neuro-oncology. The models discussed include brain tumors produced by local implants of carcinogenic hydrocarbons and by the administration of resorptive N-nitroso compounds, some of the cell lines derived from the latter, tumors resulting from the intracerebral inoculation of oncogenic viruses, and the differentiating neuroepithelial component of a transplantable mouse teratoma. The structural and biochemical criteria that can be applied for the identification of the various stages of neuronal and glial cell maturation are highly precise. They reveal a wide diversity of tumor cell types that are now available in experimental neuro-oncogenesis.

Animals↗
PubMed1979

Solid tumor models for the assessment of different treatment modalities: VIII. The scheduling of treatment for a chemotherapeutically resistant experimental solid tumor.

Single, large doses of adriamycin, cyclophosphamide and 5-fluorouracil (5-FU) have been compared to the same amount of drug given in divided doses daily over a 3 or 5 day period in a solid tumor model which metastasizes to the regional lymph nodes and lungs. No significant increase in life expectancy occurred following adriamycin or cyclophosphamide. However, a significant reduction in life expectancy occurred after 5 fractionated doses of 5-FU but not after the large single dose. The increase in mortality following fractionated doses of 5-FU is attributed to the prolongation of the onset of recovery of bone marrow. Tumor volume reduction following a single dose of each agent was equal to or greater than the fractionated doses. The results of these studies on this chemotherapeutically resistant solid tumor indicate that small daily fractionated doses of adriamycin, cyclophosphamide or 5-FU result in increased morbidity and mortality without therapeutic benefit in tumor control. The time sequence of recovery of the limiting organ of the host (i.e., bone marrow) is similar to the time sequence of recovery of the tumor. Large intermittent single doses of chemotherapeutic agents given following recovery of the host from a previous treatment would be expected to be less toxic to the host and equally effective in control of tumor growth. None of the 3 chemotherapeutic agents was successful in tumor eradication. Previous studies of this series have shown that the utilization of sequential chemotherapy combined with radiotherapy can be successfully used for eradication of another solid tumor which did not metastasize. A similar therapeutic strategy using sequential combined modality therapy should also be effective in the control of the primary H-4-II-E tumor as well as its metastatic dissemination. Information gained from these experimental studies should eventually provide information which should be helpful in the clinical management of chemotherapeutically resistant solid tumors in man.

Animals↗
PubMed1978

Comparative effects of Corynebacterium parvum, Brucella abortus extract, Bacillus Calmette-Guérin, glucan, levamisole, and tilorone with or without cyclophosphamide on tumor growth, macrophage production, and macrophage cytotoxicity in a murine mammary tumor model.

In this laboratory, it has been repeatedly demonstrated (using a murine mammary tumor model) that the combination of cyclophosphamide (CY) and Corynebacterium parvum (CP) is more effective than either agent alone in the control of tumor growth. This paper presents information obtained in our model comparing findings on the effects of CP with a Brucella abortus extract (Bru-Pel; BP) and glucan (GL) on tumor growth. In addition, the influence of those agents as well as bacillus Calmette-Guérin, tilorone, and levamisole on bone marrow macrophage colony production and cytotoxicity is presented. None of the nonspecific stimulating agents (NSSAs) inhibited tumor growth when administered systemically without CY, confirming our previous contention that such immunotherapy alone is likely to be an ineffectual form of treatment. Whereas tumor regression was observed following intratumor CP, neither GL nor BP had such an effect. When used with CY, neither BP nor GL administered ip or intratumorally inhibited tumor growth as effectively as did CP and CY. Inhibition of the growth of a distant tumor as well as the treated tumor occurred following intratumor CP and CY but not following intratumor BP and CY. All of the microbial NSSAs increased macrophage colony production to varying degrees in both normal and tumor-bearing mice. In the latter mice, CP had the most prolonged effect. Levamisole and tilorone failed to increase colony production in normal mice while in tumor-bearing mice the effect was inversely proportional to the amount of agent administered. To some extent, the stimulation of colony production by the NSSAs paralled the degree of tumor inhibition observed when those agents were combined with CY. The cytotoxicity of cultured macrophages could not be related to tumor growth inhibition.

Animals↗
PubMed1979

Development of a metastatic brain tumor model in mice.

This study reports an easily accomplished and reliable model of metastatic tumor in the brains of mice. Five experimental groups of female C3H/Bi mice received left intracardiac injections of a syngeneic KHT sarcoma cell suspension (1 X 10(5) cells) and were followed until death. Two groups of mice also received 3,000 rads of radiation to a limited cardiac port 24 hr after tumor injections. All mice were completely autopsied, and the brains were examined both grossly and microscopically. Metastatic brain tumor developed in 60 to 70% of mice; the tumor foci were parenchymal, usually multifocal, and had wide distribution throughout the cerebrum, brainstem, and cerebellum. There was occasional meningeal tumor, but tumor never involved the skull, choroid plexus, pituitary gland, or local extracranial structures. Cardiac irradiation did not increase the number of the mean survival of mice with metastatic brain tumor but did decrease the total tumor burden of individual animals by markedly reducing the incidence of metastatic lung tumor and totally preventing tumor infiltration of the heart. This demonstration of consistently produced blood-borne metastatic brain tumor in mice should provide a valuable research model which will allow the central nervous system to be studied for internal mechanisms and/or external factors which influence the arrest and growth of embolic tumor cells in the brain.

Animals↗
PubMed1977

Brain-tumor chemotherapy. Pharmacological principles derived from a monkey brain-tumor model.

An implnated choriocarcinoma growing inthe brains of monkeys was used as a brain-tumor model for the study of the cerebral distribution of two commonly used physiological markers, inulin and albumin; tissue samples were obtained from the tumor, adjacent brain, and distant brain. An extravascular inulin space was calculated by subtracting the albumin (plasma) space from the total inulin spaces. The extravascular inulin space in the tumor was found to be 24%, a value significantly larger than that in distant brain (0.6%). The large inulin space of the tumor was probably the result of increases on both capillary permeability and the extracellular space within this area. Determination of the inulin space in 1 to 2-mm thick samples of tissue taken serially from the tumor center to the distant brain indicated a gradual decline in inulin concentration from the tumor's edge to distant brain. This distribution pattern could be the result of either a continuous decrease, running from the tumor to distant brain, in capillary permeability to inulin, or a diffusional flow of inulin from the tumor into the adjacent tissue. The failure of drugs to inhibit such a tumor in view of these observations is discussed.

Albumins↗
PubMed1975

Characterization of a Wilms' tumor model.

Growth characteristics, survival time, sex differences and hormonal effects, and various biochemical parameters were evaluated in a transplantable Furth/Wistar rat Wilms' tumor model. Survival time was dependent on site of tumor transplant and ranged from a mean of 28 days for intrarenal implantation to 44 days intramusculary. Maximum tumor weight (130 g) was obtained via subcutaneous implant. Lung metastasis was evident in the majority of animals with the exception of those receiving the tumor implant intraperitoneally. The levels of erythropoietin and serum calcium and phosphatase were comparable to control values whereas hematocrit levels declined. Tumor tissue arginase or total protein remained unchanged during tumor growth. In these same tissues DNA, content and 5-alpha-reductase activity significantly and progressively increased with concomitant tumor growths. Measurements of lactic dehydrogenase, alkaline phosphatase, and their isoenzymes indicated patterns of liver involvement which were not macroscopically evident. After 31 days of subcutaneous tumor transplant, male and female rats had tumors of comparable weights. Orchiectomy or estradiol treatment significantly reduced tumor weight in males. In female rats testosterone treatment significantly increased tumor weights. DNA concentration in tumor tissue was unaffected by treatment. Similiarly, although 5-alpha-reductase activity was higher in tumors from males, and arginase higher in females, these enzymes were not affected by surgical or hormonal treatment.

Animals↗
PubMed1975

Evaluation of antitumor activity of Bordetella pertussis in two murine tumor models.

The antitumor activity of three preparations of killed Bordetella pertussis (Bp) (Eli Lilly crude and fluid pertussis vaccines and Parke-Davis pertussis vaccine) was studied in the B16 melanoma and CaD2 mammary adenocarcinoma models. In these tumor systems; Bp had weak and variable tumor inhibitory activity and did not augment tumor rejection immunity. The intratumor injection of Bp did not affect the growth of the B16 tumor but significantly inhibited the growth of the CaD2 tumor. However, the established tumor did not regress. Admixture of Bp with B16 cells before inoculation inhibited tumor growth and prolonged survival of inoculated mice. Admixture of Bp with CaD2 cells completely suppressed tumor cell growth in 60% of inoculated mice. Intratumor injection of CaD2 with Bp combined with surgery provided no protection against subsequent development of metastases.

Adenocarcinoma↗
PubMed1976

Plasma levels of a viral protein as a diagnostic signal for the presence of tumor : the murine mammary tumor model.

We used the mouse mammary tumor and its associated virus (murine mammary tumor virus) to examine the possibility of using plasma levels of a viral protein (gp52, the glycoprotein of 52,000 molecular weight) as a diagnostic indicator of the presence of a solid tumor. The following features have emerged from our studies: (a) tumor-bearing animals show markedly elevated (100-1000 ng/ml) plasma levels of gp52 and the mean concentration increases with tumor size; (b) mammary tumor tissues located outside the mammary gland are also detected by the elevated plasma gp52; (c) low (2-10 ng/ml) plasma levels of gp52 are found in tumor-free mice, whether they are derived from strains characterized by high or low frequencies of spontaneous mammary tumors; (d) tumor-free lactating females exhibit the normally low levels of plasma gp52 despite the fact that their milk contains an average of 20,000 ng/ml of this antigen; (e) thus, high levels of plasma gp52 are found only in the presence of tumor and are not induced by either predisposition for the disease or by normal production of the antigen during lactation; (f) the circulatory clearance time of gp52 is sufficiently rapid to require continued replenishment to maintain the high levels observed in tumor-bearing animals, a feature implying that the gp52 concentration can be a responsive parameter of disease status. The information obtained suggests that plasma gp52 is a potentially useful and specific systemic indicator of the presence and extent of murine mammary neoplasia.

Animals↗