Relationship Between Temperature and Blood Supply or Consumption of Oxygen and Glucose by Rat Mammary Carcinomas

Gullino, Pietro M.; Yi, Pon-Nyong; Grantham, Flora H.

doi:10.1093/jnci/60.4.835

Cited by 40 publications

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“…Gullino et al (1982) reported that S.C. tumors in normothermic rats have a circadian temperature rhythm with the zenith at midnight and nadir at mid-day. The data of Gullino et al (1978Gullino et al ( , 1982 and our own data suggest that there might be close correlations between metabolic activity and blood flow in tumors. It has been reported that the larger the tumor is, the lower is tumor tissue blood flow (Vaupel et al, 1987;Kallinowski et al, 1989; al., 1 9 9 3~) .…”

Section: Discussionsupporting

confidence: 57%

Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow

Hori

Zhang

et al. 1996

Int. J. Cancer

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Blood flows of normal tissues (subcutis, liver, kidney cortex, bone marrow) and tumor tissues (SLC) were measured during a daytime period (3-9 HALO) and a nighttime period (15-21 HALO) by the hydrogen clearance technique. Rats were subjected to an artificial light-dark cycle with light from 7 A.M. to 7 P.M. In all normal tissues, there were no significant differences between average tissue blood flows in 2 different time zones, while tumor tissue blood flow increased significantly in the nighttime. Based on this functional characteristic of tumor microcirculation, anti-tumor effects were compared between a group in which ADM was administered at 4 HALO and a group in which it was administered at 16 HALO. The therapeutic effect of ADM on rats administered at I 6 HALO was significantly greater, particularly in large tumors, than that on rats administered at 4 HALO. The main reason for this therapeutic improvement may be due to the selective increase in delivery of anti-cancer drugs to tumor tissues brought about by a circadian increase in tumor tissue blood flow. o 1996 Wiley-Liss, Inc. We have discovered circadian fluctuations in tissue blood flow of S.C. rat tumors (Hori et al., 1992), and the time during which tumor tissue blood flow increases coincides with the time during which tumor growth becomes more rapid (Hori et al., 1995). It has also been reported that there are circadian fluctuations in DNA synthesis of tumor cells (Smaaland et al., 1993; Hrushesky and Bjarnason, 1993). The fact that tumor tissue blood flow and tumor growth vary during a 24-hr time period supports the idea that there may be an optimal time for the administration of anti-cancer drugs. Because commonly used anti-cancer drugs exert their greatest effects when cancer cells are actively dividing and/or in specific phases of the cell cycle, if an anti-cancer drug could be delivered to tumor tissue when the proliferation of cancer cells is at its peak, then its therapeutic effect would be further increased. The purpose of this study was to confirm the importance of the circadian timing of cancer chemotherapy. We measured the tissue blood flows of normal organs and tumors during the nighttime and the daytime. Furthermore, we investigated whether the efficacy of cancer chemotherapy is enhanced by administering anti-cancer drugs when tumor tissue blood flow increases. MATERIAL AND METHODS Rats and tumor Male Donryu rats (Crj-Donryu; Nippon Charles-River, Yo-kohama, Japan), weighing approximately 300-340 g each, were used for tissue blood flow measurements. The same strain of rats, weighing approximately 230-260 g each, was used for the chemotherapy experiments. Rats were caged in an air-conditioned room at a temperature of 25 & 1°C and given food and water ad libitum. For 3 weeks prior to measurement they were subjected to an artificial light-dark cycle, with light from 7 A.M. to 7 P.M. Rodents are nocturnal. In fact, rats under this condition were in full activity during the nighttime, though they slept well during the daytime. The tumor cells...

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Section: Discussionsupporting

confidence: 57%

Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow

Hori

Zhang

et al. 1996

Int. J. Cancer

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“…The model of Gullino and Grantham [7] has up to now mainly been used as a method of evaluating tumor metabolism in vivo [6,8,21]. Tumor inoculates in the kidney grow in a predictable way that produces tumors of a suitable and convenient size.…”

Section: But the O T H E R Enzymes Acting On Glucose 6-p H O S P H A mentioning

confidence: 99%

Tumor localization with18F-2-fluoro-2-deoxy-D-glucose: Comparative autoradiography, glucose 6-phosphatase histochemistry, and histology of renally implanted sarcoma of the rat

Paul¹,

Johansson

Kellokumpu‐Lehtinen

et al. 1985

Res. Exp. Med.

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Rous sarcoma cells were implanted into the kidney of rats. After 5 days of growth the renal tumor was used for comparing histology with glucose 6-phosphatase (G6Pase) enzyme histochemistry (EHC) and 18F-fluoro-2-deoxyglucose (FDG) auroradiography (ARG). It was found that the regions of the kidney tumor that had retained normal kidney structures were devoid of FDG, whereas there was histochemical staining of normal cortical areas. Regions of tumor growth, on the other hand, retained FDG and lacked G6Pase. Necrotic areas did not accumulate FDG. There was a dramatic decrease in the areas of G6Pase activity as a result of tumor infiltration in the kidney. The results show that FDG, currently being evaluated as a tumor detecting radiopharmaceutical indeed accumulates into areas of vital malignant growth, and they indicate that FDG positron emission tomographic (PET) images reveal the true anatomic location of malignant tissue.

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“…The current evidence indicates, however, that there is a considerable variation in these effects of oxygen depending both on the cell line used and the conditions of spheroid growth and treatment (Durand, 1980; Mueller-Klieser and Sutherland, 1982b;Mueller-Kleiser et al, 1983).The reason for the development of a steady-state oxygen concentration gradient in spheroids or tumors is the oxygen consumption of the cells, and many factors which are changing during the growth of cells as spheroids can have an effect on the rate of cellular oxygen utilization. These include extracellular influences, such as metabolite and catabolite concentrations (Ibsen, 1961;Guillino, 1978), as well as cellular variables such as size and proliferation. Previous work by our group (Freyer et al, 1984) has demonstrated that the oxygen consumption rate of cells in V-79 spheroids decreases fourfold during growth from 150 to 600 pm in diameter.…”

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confidence: 99%

A reduction in the in situ rates of oxygen and glucose consumption of cells in EMT6/Ro spheroids during growth

Freyer

Sutherland

1985

Journal Cellular Physiology

178

121

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The rates of consumption of oxygen and glucose by EMT6/Ro cells in multicellular spheroids were measured at various times during normal growth. In situ spheroid cellular consumption rates were similar to those of exponentially growing single cells up to a spheroid diameter of 150 micron. Further growth resulted in decreases in the rates of both oxygen and glucose consumption which were correlated with the increase in spheroid diameter and cell number. At a diameter of 1300 micron, both rates of cellular consumption had decreased by a factor of 2.5. The rates of consumption per unit of nonnecrotic spheroid volume decreased in a similar manner. Measurements with single cells demonstrated that the rate of oxygen consumption was coupled with glucose concentration, and vice versa. The rates of consumption for cells dissociated from small spheroids indicated that there was some effect of the spheroid environment. As the spheroids grew, however, association in the spheroid structure accounted for a smaller proportion of the total observed reduction in the rates of nutrient consumption. The presence of central necrosis also appeared to have no effect on the rates of consumption of these nutrients. Spheroid-derived cells showed a decrease in cell volume with growth as the cells accumulated in a quiescent state. Measurements with single cells demonstrated that oxygen and glucose consumption were correlated with cell volume and with the development of nonproliferating cells. We conclude that the observed decrease in oxygen and glucose consumption with growth in spheroids is largely due to the progressive accumulation of cells in a quiescent state characterized by an inherently lower cellular rate of nutrient utilization.

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Relationship Between Temperature and Blood Supply or Consumption of Oxygen and Glucose by Rat Mammary Carcinomas

Cited by 40 publications

References 0 publications

Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow

Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow

Tumor localization with18F-2-fluoro-2-deoxy-D-glucose: Comparative autoradiography, glucose 6-phosphatase histochemistry, and histology of renally implanted sarcoma of the rat

A reduction in the in situ rates of oxygen and glucose consumption of cells in EMT6/Ro spheroids during growth

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