The Dose-response Relationship Between the Number of Embolic Tumor Cells and the Incidence of Blood-borne Metastases

Baserga, Renato; Putong, Paul B.; Tyler, Sylvanus A.; Wartman, William B.

doi:10.1038/bjc.1960.21

Cited by 16 publications

(4 citation statements)

References 10 publications

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“…It is known that micrometastases reach the liver through the portal venous system by invasion of the mesenteric veins (Brown & Warren, 1938;Dukes, 1.940;Fisher & Turnbull, 1955;Fisher & Fisher, 1959;Baserga et al, 1960). While the developing metastases are small they continue to obtain their nutrition from the portal vein, but as they enlarge the blood supply is thought to be chiefly arterial (Ackerman, 1972).…”

mentioning

confidence: 99%

The blood supply of colorectal liver metastases

Taylor¹,

Bennett²,

Sherriff³

1978

Br J Cancer

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Summary.-Post-mortem studies suggest that liver metastases obtain the majority of their nutrition from the hepatic artery; however, cytotoxic arterial perfusion with or without hepatic-artery ligation has not proved entirely successful as a therapeutic regime.In this study we have measured blood flow into colorectal liver metastases using xenon-133 (133Xe) clearance in patients undergoing surgery for colorectal cancer.Pre-operative measurements after direct parenchymal injection gave a mean flow of 41-5 i 22.5 ml/min/100 g which after hepatic arterial occlusion perfusion, was reduced to a mean of 5o% of the pre-occlusion value.Dynamic blood-flow studies using the gamma camera were performed in the postoperative period by administration of 133Xe into both hepatic arterial and portal venous catheters. The initial distribution images indicated a predominant arterial perfusion to the metastases, but after hepatic-artery ligation, portal-vein perfusion to the metastases was statistically significantly increased.Hence, a compensatory haemodynamic mechanism exists which may account for the poor results of hepatic-artery ligation and perfusion alone.

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mentioning

confidence: 99%

The blood supply of colorectal liver metastases

Taylor¹,

Bennett²,

Sherriff³

1978

Br J Cancer

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“…SINGLE tumour cells, prepared in suspension from certain transplantable ascites and solid tumours and injected intravenously, have been shown to form tumour macrocolonies in the lungs of mice and rats (Zeidman, McCutcheon and Coman, 1950;Baserga et al, 1960;Williams and Till, 1966;Hill and Bush, 1960). The number of macrocolonies produced was found to be proportional to the number of cells injected, but colony forming efficiencies (CFE) reported in the literature varied considerably and were relatively low compared with plating efficiencies obtained in vitro (Williams and Till, 1966).…”

mentioning

confidence: 99%

Macrocolony Assays in the Rat of Allogeneic Y-P388 and W-256 Tumour Cells Injected Intravenously: Dependence of Colony Forming Efficiency on Age of Host and Immunity

Brenk¹,

Sharpington²,

Orton³

1973

Br J Cancer

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Summary.-Two rapidly growing allogeneic tumours, sublines of Yoshida (Y-P388) and Walker (W-256) injected intravenously in single cell suspensions produced tumour macrocolonies in the lungs of rats within 7 days. Y-P388 produced similar but fewer colonies in the kidneys. Colony forming efficiency (CFE) in lung was high in weanling rats given either sublethal whole body irradiation (WBI) or a single dose of rabbit anti-rat lymphocytic serum (ALS) to suppress immunity. In immunologically intact weanlings CFE was much lower and many 7-day old colonies showed signs of regression. CFE for primary tumour cell challenges decreased rapidly and markedly with increase in age of host during the first 1-2 weeks after weaning. This resistance to growth of a primary challenge in lungs of older rats was not significantly reduced by WBI but was decreased by ALS. CFE of a secondary challenge of tumour cells injected intravenously in rats which had been previously immunized with heavily irradiated (HR) tumour cells was very low; it was not significantly increased by WBI but was moderately increased by ALS. In weanling rats given lethal (900 ra4) WBI, 1 hour before intravenous injection of tumour cells, treatment with bone marrow (BM) cells derived from normal adult donors increased CFE, whereas BM (or spleen) cells from immunized donors decreased CFE. The results suggest that ALS and WBI not only increase tumour CFE by suppressing immunity to tumour growth but also " condition " host tissue (tumour bed) in such a way as to facilitate the survival, " take " and initial replication of grafted tumour cells before the rats recover from the immunosuppressive effects of these treatments.

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“…For these purposes, different doses of viable Ehrlicli ascites tumor cells were injected into the tail vein of mice of both sexes. The incidence and number of lung metastases in each group was determined by actual count and the weights of the lungs, spleen, liver and kidneys were used to establish a quantitative index of the response of the reticuloendothelial system to the presence of tumor metastases [98]. The Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract.…”

Section: Tumours and Metastasesmentioning

confidence: 99%

Toxicogenomics and cancer pathogenesis

Gupta¹,

AK²,

Boraste³

et al. 2009

Int J Genet

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Abstract-Toxicogenomics is emerging field give idea of the application of large-scale differential gene expression data to toxicology, starting to influence drug discovery and development in the pharmaceutical industry. Its future potential in cancer pathogenesis, study of poisons and poisoning and has an ancient and venerable history. Toxicogenomics is the merging of toxicology with technologies that have been developed, together with bioinformatics, to identify and quantify global gene expression changes for gene therapy. Immunotoxic processes and the development of in vitro screening assays is therefore expected to be of value for mechanistic insight into immunotoxicity and hazard identification of existing and novel compounds. Successful application of toxicogenomic approaches, such as DNA microarrays, inextricably relies on appropriate data management, the ability to extract knowledge from massive amounts of data and the availability of functional information for data interpretation. Toxicogenomics is considered a valuable tool for reducing pharmaceutical candidate attrition by facilitating earlier identification, prediction and understanding of toxicities. Pharmaco-epidemiological (toxicogenomics) data is now available for both antiepileptic drugs, evidence for human carcinogenicity. Therapeutic researches converge triad of rejuvenation, regeneration or replacement strategies that rely on self-healing processes, stem cell regeneration organ transplantation. Metastases studies usually display more genetic changes than the primary tumour. Helix-loop-helix application in translational and functional toxicogenomics transcription factors has been implicated in diverse cellular processes such as proliferation, apoptosis, differentiation, and migration.

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The Dose-response Relationship Between the Number of Embolic Tumor Cells and the Incidence of Blood-borne Metastases

Cited by 16 publications

References 10 publications

The blood supply of colorectal liver metastases

The blood supply of colorectal liver metastases

Macrocolony Assays in the Rat of Allogeneic Y-P388 and W-256 Tumour Cells Injected Intravenously: Dependence of Colony Forming Efficiency on Age of Host and Immunity

Toxicogenomics and cancer pathogenesis

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