Vascular clearance of particulate substances: function of the reticuloendothelial system or measurement of liver blood flow? Invited commentary.
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Humans↗
Biomedical subjects
S B Holmberg
Publications and source records attributed to S B Holmberg.
[The man behind the syndrome. Denis Burkitt. He surveyed malignant lymphoma in African children--also a pioneer in dietary fiber research].
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Africa, Eastern↗
Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts.
The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.
Adenocarcinoma↗
Macrophage function and surgery. A clinical review with special reference to phagocytosis.
Present knowledge of macrophage phagocytosis in the context of surgical trauma is reviewed. The historical and morphologic background of the reticuloendothelial system and the mononuclear phagocyte system is surveyed. The physiology of the phagocytic process and methods of measurement are summarized and the influence on phagocytosis of shock, sepsis, cancer, parenteral nutrition and surgical procedures such as liver resection and splenectomy is discussed. Conclusions are that multiple factors may depress macrophage phagocytosis during surgery and that, in order to maintain immune defence balance, traumatic manipulation of tissue and abdominal organs must be minimized.
Humans↗
[Chemoprevention of cancer. Epidemiology and basic research point to new directions].
Cancer transformation of normal cells has been shown to be a multistep procedure, where a primary change is initiated by endogenous or exogenous alteration in nuclear DNA. Further activation of oncogenes or deletion of tumor suppressor genes is then required to transform the normal cell to a proliferating cancer cell. This process requires many years in humans. Epidemiological evidence and case-control studies have pointed to substances with a potential as cancer chemopreventative. Basic science has elucidated possible mechanisms on initiation and promotion of carcinogenesis behind the chemopreventive action of retinoids, other vitamins and selenium. These substances are presently being investigated in intervention studies to prevent cancer in high risk groups and the general population.
Cell Transformation, Neoplastic↗
Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.
Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Albumins↗
[Cancer information for the public and for health personnel].
The increasing amount of knowledge about all aspects of cancer needs to be communicated to both health personnel and patients. In the United Kingdom and the USA information centers have been established. The Cancer Information Service in the US, funded by the National Cancer Institute and the British Association of Cancer United Patients (BACUP) funded by the Cancer Research Campaign provide telephone and mail service. The Information Centers offer counseling, general cancer information and information on treatment options and clinical trials. Health personnel can subscribe to a monthly updated Physician Desk Query (PDQ) with information on more than 75 different cancers, staging, treatments, prognosis, clinical trials and treatment centers. Evaluations in the US and UK have shown high satisfaction with the Information Services.
England↗
[A growing research interest in liver sinusoidal cells].
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Humans↗
Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.
This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.
Adenocarcinoma↗
RES function and tumour take and tumour growth in the liver and in the kidney--an experimental study in rats.
This experimental study in rats examines tumour take and growth after RES modulation in an organ rich in macrophages--the liver--vs. an organ poor in macrophages--the kidney. A control group of 16 rats had 1.0 X 10(6) transplantable adenocarcinoma cells inoculated in the liver and the same number in the left kidney. They were compared with a RE-stimulated group of 16 rats treated i.v. with Zymosan (3 mg/100 g for 3 days) and a RE-depressed group of 16 rats treated with i.v. methylpalmitate (100 mg/100 g for 3 days) before tumour inoculation. Tumour size was measured on days 7 and 14. The animals were killed on day 14. Mortality was significantly higher in methylpalmitate-treated rats than in control groups. Tumour take in the kidney was not affected by RES stimulation or depression. In the liver, RES stimulation caused significantly less tumour take. Depression of RES with methylpalmitate did not increase tumour take or tumour growth in the liver, which was very high in the control group.
Adenocarcinoma↗
Phagocytosis and dynamic RES scintigraphy: an evaluation of commercial colloids in rats.
Reticuloendothelial system (RES) phagocytic function or capacity can be measured by clearance studies with test substances. This study in the rat examines three commercially available 99Tcm-labelled test substances, and different methods of calculating RES capacity. Albures size 500 nm and sulphur colloid size 600 nm used for liver scintigraphic imaging and Nanocoll size 50 nm used for bone-marrow scintigraphic imaging were tested. The rats were examined under a gamma camera and the uptake by the liver, clearance from the heart and clearance from blood samples were recorded. Different amounts of substances were tested. The final uptake in different organs was recorded after the animals were sacrificed. Colloid size and stability were tested with a polycarbonate filter. (Nanocoll was found to have at least 10 times smaller colloid diameter, leading to a thousand times more particles per milligram). RES function was calculated as the uptake rate or clearance rate, k. In a logarithmic plot, the relationship between uptake or clearance and time was found to be linear between 90 and 300s and calculations of k in this interval are recommended. k-values selected from blood sample curves were 11 +/- 5 S.E.M. lower than those calculated from heart clearance curves or liver uptake curves. Increasing amounts of Nanocoll caused a decrease in uptake rate k. Albures and sulphur colloid could not be given in amounts that caused any change in k. Only Nanocoll could be given in sufficiently large amounts (above the critical dose) to challenge RES and avoid complete extraction from the circulation during first passage through RE organs. Nanocoll seems suitable for use in tests of RES function and the optimal amount was 0.03 mg per rat (0.6 X 10(12) particles).
Animals↗
Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.
Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.
Allopurinol↗
Tumour adjacent macrophage function in experimental tumours.
This study describes in vivo methodology for evaluating whole body and Tumour Adjacent Macrophage (TAM) phagocytic function in tumour-bearing rats. 29 Wistar rats were inoculated with 1 x 5 mm cylinders of syngeneic NGW-adenocarcinoma im in the right hind leg. 10 rats were given iv zymosan (3mg/100 g b.w.) for systemic activation of macrophages, 9 rats were given intratumour injection of zymosan (3mg/100g b.w.) for local activation and 10 rats were untreated controls. 10 days after tumour inoculation whole body phagocytic rate was estimated with dynamic liver RES scintigraphy. Tumour and blood radionuclide activity was measured. Dynamic liver RES scintigraphy measures whole body macrophage phagocytic rate (k) of iv 99Tcm Nanocoll albumin test colloid. TAM phagocytic rate is calculated from the final uptake in tumor/injected dose x k. Systemic macrophage activation caused a significant increase in liver and spleen weight and whole body phagocytic rate (0.65 +/- 0.02 versus 0.56 +/- 0.03% s-1). The TAM phagocytic rate was significantly elevated in tumors treated by local macrophage activation (0.003 +/- 0.00 versus 0.001 +/- 0.00% s-1). This study suggests that the TAM phagocytic rate is a sensitive indication of local macrophage activity.
Adenocarcinoma↗
RES-macrophage stimulation and liver tumour growth in rats; evaluation with dynamic liver RES scintigraphy.
Dynamic liver RES scintigraphy with Nanocoll (99Tcm albumin colloid - 50 nm diameter) assessing RES-macrophage phagocytic function was performed in 40 control, 73 RES-stimulated non-tumour-bearing and 59 tumour-bearing Wistar/FU rats in vivo. Tumour-bearing rats were inoculated with 10(6) x 1.0 cells of a syngeneic nitrosoguanidine-induced colonic carcinoma in the liver. Twenty-eight of these rats had been treated one day previously with Zymosan (3 mg x 100 g-1 i v) as a RES stimulant. The clearance/uptake rate (k) of Nanocoll was calculated from dynamic liver images by the slope in the plot 1n [1 - U(t)/U] versus t where t is time and U liver uptake. k-value in control animals was 0.45 +/- 0.01.10(-2) x s-1 Zymosan injection in non-tumour-bearing rats caused stati-stically significant higher clearance/uptake rate on day 1, through 8 after treatment compared to that of controls. On day 8 k-value was 0.64 +/- 0.04. In tumour-bearing rats the uptake rate (k) was on day 8 0.66 +/- 0.03, while in RES-stimulated tumour-bearing rats it was 0.64 +/- 0.03. Survival was 22 +/- 1 days in tumour bearing rats and 37 +/- 4 days in RES stimulated tumour-bearing rats. The average tumour volume after one week was 132 +/- 24 mm3 in non-stimulated rats and 20 +/- 5 mm3 in RES stimulated rats. There was a negative correlation between uptake rate and tumour volume and a positive correlation between uptake rate and survival on day 8 in non-stimulated tumour-bearing rats. Dynamic liver RES scintigraphy with small size 99Tcm albumin colloid (Nanocoll) can be used to measure RES phagocytic function and the effect of liver tumour growth on RES.
Adenocarcinoma↗
Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.
Adenocarcinoma↗