Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 micrograms AII over 90 s. Six patients with isolated small metastases (< 5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of AII infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following AII infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of AII and other vasoconstrictors to enhance targeting precision.
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PMID:Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II. 141 43

Colorectal hepatic metastases have a notoriously poor response to conventional systemic chemotherapy. We have synthesised cytotoxic drug (doxorubicin and mitomycin C) containing spheres 40 microns in diameter, using human albumin and ethyl cellulose as matrices. Introduction of these cytotoxic microspheres into the hepatic artery should embolise to the tumor and provide a controlled release depot for the anticancer agent. The vasoconstrictor, angiotensin II (AII) has been shown to increase tumor blood flow relative to normal tissue when administered via the hepatic artery, therefore we have investigated the effect of AII on targeting of cytotoxic microspheres to hepatic metastases. Patients with hepatic metastatic colorectal carcinoma had hepatic arterial catheters inserted at laparotomy and connected to subcutaneous injection ports. Peroperatively, 99mTc-labelled albumin microspheres were administered via the arterial catheter. Fifteen minutes later, AII was infused (10 micrograms per minuter for 4 min) via the catheter and 131I-labelled albumin microspheres were administered as a bolus at the midpoint of the AII infusion. Multiple biopsies were taken of normal liver and tumor metastasis and the tissue radioactivity counted for 99mTc and 131I. Further studies were performed postoperatively in which 99mTc-labelled microspheres were administered via the hepatic artery catheter and their distribution was followed using tomographic SPECT scanning. Combined results of this study suggested that AII can increase tumor SPECT scanning. Combined results of this study suggested that AII can increase tumor blood flow rates relative to normal hepatic tissue by approximately 3-fold.
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PMID:The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs. 161 36

To evaluate the use of angiotensin-II (A-II) as a means of improving results with intra-arterial infusions of hepatic tumors, 32 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine [( 3H]FUDR) was administered via peripheral ear vein in 9 control rabbits (iv), via the hepatic artery in 12 rabbits (HA), and following a constant infusion of A-II in the remaining 11 rabbits (HA/A-II). Biopsies of tumor and normal hepatic parenchyma were taken and tissue levels of FUDR measured. Hepatic artery infusions, both with and without A-II, resulted in a significantly greater tumor uptake of FUDR than the iv infusions (P less than 0.001). More importantly, the tumor/liver ratio of FUDR uptake was significantly greater in the HA/A-II group (3.40) than that in the HA without A-II (0.98) group (P less than 0.001). This difference is due to the decreased FUDR uptake by normal hepatic parenchyma in rabbits undergoing A-II infusion; tumor drug uptake is similar for both groups. We conclude that the addition of angiotensin II to hepatic artery infusional chemotherapy significantly improves the tumor/liver ratio of drug uptake in this experimental model of hepatic metastases.
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PMID:Angiotensin alteration of drug uptake in an experimental model of hepatic metastases. 183 Sep 15

A study was made of the response rates of primary and metastatic lesions of advanced gastric cancer patients receiving chemotherapy from 1978 to 1987. The patients administered adriamycin (ADR), 5-FU, mitomycin C (MMC) or their analogues showed a response rate of 12.2% (5/41) in primary lesions, 15.9% (7/44) in liver metastases and 20.0% (4/20) in lymphnode metastases, respectively. The response rates were 14.3% (5/35) in primary lesions 16.7% (6/36) in liver metastases and 12.5% (2/16) in lymphnode metastases from chemotherapy using at least two kinds of the above drugs. No significant difference was seen among the response rates per above. By elevating blood pressure induced with angiotensin II, selective increase in blood flow in tumor tissue but no increase in normal tissue was observed experimentally (JNCI, 67, 663, 1981). This finding was clinically applied to cancer chemotherapy, termed Induced Hypertension Chemotherapy (IHC) for enhancing selective drug delivery to tumor tissue. The response rates were 47.6% (10/21) in primary lesions, 28.6% (2/7) in liver metastases and 81.8% (9/11) in lymphnode metastases when combination chemotherapy mainly with ADR, 5-FU and MMC with IHC was performed. Although the response rates were better than the results without IHC, the liver metastases did not indicate any statistical differences. The metastatic lesions in the lymphnode indicated a higher response than that of the primary lesions in the group treated with IHC, but no significant difference was seen. As to the primary lesions and the lymphnode metastases, the treatment with IHC showed higher response rates than those without IHC. It is conceivable that the results obtained would clinically prove the mechanism of selective drug delivery to tumor tissue as described in the experiment stated above. To detect the cause of unsatisfactory response rates of liver metastases, further clinical analysis of accumulated cases may be required.
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PMID:[Chemotherapeutic effect on metastatic tumors]. 249 64

Although hypertension is the major cause of left ventricular hypertrophy (LVH), numerous studies failed to demonstrate a close correlation between resting blood pressure (BP) and degree of LVH. Some authors have shown better correlation between BP at work and left ventricular mass (LV mass), whereas other studies supported an association between catecholamines or angiotensin II and LV mass. In this study we investigated the relationship of resting and exercise BP and catecholamines to the degree of LVH. Nineteen patients with established mild to moderate hypertension were studied. Blood pressure was measured following a ten-minute rest and every three minutes during exercise using a Bruce protocol. Electrolytes, epinephrine (EP), and norepinephrine (NE) were measured at rest, at peak exercise, and at ten-minutes postexercise. Resting BP averaged 154 +/- 24/99 +/- 9 mm Hg and at three minutes of exercise 195 +/- 30/101 +/- 6 (P less than .001). Resting EP was 51 +/- 20 pg/mL, NE 314 +/- 187, and at peak exercise EP was 107 +/- 61 (P less than .001) and NE 1016 +/- 566 (P less than .001). The average LV mass was 277 +/- 85 g. A significant correlation was found only between systolic BP at three minutes of exercise and LV mass (r = .479, P less than .04). No other variable correlated significantly with LV mass. These data suggest that systolic BP achieved at low level of exercise (5 mets), corresponding to usual daily activities, may be the most important determinant of LVH in patients with hypertension.
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PMID:Exercise blood pressure response and left ventricular hypertrophy. 252 91

The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.
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PMID:Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease. 281 38

A 47-year-old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11-deoxycorticosterone and corticosterone in addition to aldosterone and 18-hydroxycorticosterone. Basal 11-deoxycorticosterone levels were particularly high. Corticosterone, 18-hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma cortisol and assays for sex hormones were normal although there was evidence that cortisol derived from the neoplasm. At operation a well-differentiated adrenocortical carcinoma weighing 50 g (56 X 30 X 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11-deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.
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PMID:Hypermineralocorticoidism due to adrenal carcinoma: plasma corticosteroids and their response to ACTH and angiotensin II. 282 95

A 63-year-old female, who had undergone sigmoidectomy for sigmoid carcinoma one year before, was admitted for multiple liver metastases. A urokinase-immobilized catheter was introduced into the proper hepatic artery via the gastroepiploic artery operatively. A daily arterial infusion of 5-FU (250 mg) was combined with a weekly arterial infusion of adriamycin (30 mg) or MMC (10 mg). After discharge, 5-FU (200 mg/day) was given orally and MMC (10 mg) was infused intraarterially every other week at an outpatient clinic. ADR or MMC was infused with angiotensin II, known to increase arterial blood supply to a malignant lesion. Ultrasonography demonstrated 35 to 50% reduction in tumor diameter. The density of metastases seen in computerized tomography became low indicating tumor necrosis. Plasma CEA level, which had initially been as high as 864 ng/ml, decreased rapidly and has remained within normal limits up to the present time. Arterial infusion chemotherapy using 5-FU, ADR or MMC in combination with angiotensin II seems to be effective in the treatment of multiple hepatic metastases from colorectal carcinoma.
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PMID:[A case of multiple liver metastases from sigmoid carcinoma treated successfully with arterial infusion chemotherapy]. 308 78

The effects of systemic infusion of angiotensin II on the distribution of blood flow in the sheep squamous cell carcinoma after transplantation to the liver were measured using tracer microspheres. The ratio of arterially introduced radioactive microspheres embolizing in tumour tissue compared to normal hepatic parenchyma was measured before and after infusion of angiotensin II. Doses of angiotensin II inducing increases in mean arterial blood pressure of 26 mmHg produced significant increases in the embolization ratio from 2.8 to 4.1:1. In addition, the ratio of microspheres gaining access to the necrotic centres of the tumours compared to the normal liver tissue significantly increased from 1.6 to 2.3:1. In terms of the technique of internal radiation therapy for hepatic metastases, the concurrent infusion of angiotensin II with injection of radioactive microspheres would result in a substantially enhanced radiation dose to liver tumours. At the same time the dose to normal tissue can be minimized.
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PMID:Effect of angiotensin II on blood flow in the transplanted sheep squamous cell carcinoma. 318 Dec 59

It has been found in experiments using rats that there is a lack of autoregulation of blood flow in tumor vessels and a selective increase of blood flow under angiotensin II-induced hypertension when the arterial blood pressure dose not exceed 150 mmHg, while there is no increase in normal tissues (Suzuki et al., JNCI:1981). On the basis of the functional difference of microcirculation, IHC has been developed clinically since 1978. In the procedure of treatment, the mean blood pressure of the patients was maintained at 140-150 mmHg when anti-cancer drugs were administered along with the continuous intravenous infusion of angiotensin II. In a randomized controlled study on gastric carcinoma treated with an AFM regimen, the response rate was 42.5% (8/21) in IHC vs. 10.5% (2/19) in non-IHC (p less than 0.05). The "initial response time" (15.5 vs. 28.8 days) and the "effective tumor reduction time" (36.7 vs. 57.5 days) were significantly shorter (p less than 0.01) in the IHC group. Frequency and grade of side effects were not different statistically. In an open trial, the overall response rate was 39.6% (54/134) and each response was closely related to the difference of drug sensitivity of tumor types. For example, it was 90.0% (9/10) in cancers of the head & neck, 66.7% (4/6) in the breast, 42.8% (12/28) in the stomach, 46.2% (6/13) in the pancreas, 23.1% (3/13) in the colon and 23.8% (5/21) in the lung. The effect on metastatic lymphnodes was 79.4% (27/34), which was higher than that of primary (48.1% : 26/54) and other organ metastases (34.6% : 18/52). Finally, this paper dealt with the problem of clinical evaluation of tumor lesions with a lot of fibrous granulation tissue and coagulative necrosis, and of the investigation of differential imaging.
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PMID:[Clinical study on angiotensin-induced hypertension chemotherapy (IHC)]. 372 61


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