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Biomedical subjects

H Strander

Publications and source records attributed to H Strander.

119 records · Page 7Linked to original sources

Low levels of endostatin in the urine from patients with malignant disease.

Endostatin, a C-terminal subfragment of collagen XVIII, and angiostatin, a family of fragments originating from the NH(2)-terminal portion of plasminogen, have been described as potent inhibitors of angiogenesis and malignant growth. We have earlier reported the presence of angiostatin fragments in urine from cancer patients. In this study, we investigated the occurrence of endostatin and the correlation between the amounts of endostatin and angiostatin in urine collected from 104 patients with different types of malignancies and in 16 controls. The amounts of endostatin were measured with a commercial immunoassay. Angiostatin fragments were quantitated by Western blot analysis. Only small amounts of endostatin were observed, both in patients and controls, and there was no significant difference in the amount of endostatin between the patients and the controls. Both endostatin and angiostatin concentrations in the urine showed a strong dependence on impaired kidney function, especially tubulus function, measured as the amount of urine alpha(1)-microglobulin. Interestingly, there was no significant correlation between endostatin and angiostatin concentrations in the patients with impaired kidney function (elevated urine albumin or urine alpha(1)-microglobulin), suggesting a possible difference in circulating concentrations of these inhibitors.

Adult↗

Radiation therapy in early glottic cancer. Analysis of 177 consecutive cases.

Early vocal cord carcinomas (TiS or T1) in a consecutive series of 177 patients treated by primary radiotherapy over a 10-year period 1970-79 at the Department of General Oncology, Radiumhemmet, Karolinska Sjukhuset, were analysed regarding treatment results. In 137 cases the tumours were invasive (T1N0M0) and in 40 cases carcinoma of in situ type (TiS). Patient were treated with cobalt 60 gamma irradiation in fractions of 2 Gy up to a total dose of 64 Gy delivered as split course (CRE=17.8). Minimum follow-up time was 5 years. Tumour recurred in 21 cases (12%). All but 4 patients were rescued by subsequent surgery, giving 98% total survival. Treatment failures after primary radiotherapy were analysed in detail. Failures could not be attributed to treatment irregularities. No difference in pretreatment tumour size was detected when cured patients were compared with patients who relapsed. Biological factors that cause a relative radioresistance are considered to be the main reason for radiotherapy failures in early glottic cancer.

Carcinoma↗

Angiostatin fragments in urine from patients with malignant disease.

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.

Albuminuria↗

Interferon as a modifier of estrogen receptors.

Interferon (IFN-alpha) increased estrogen receptor (ER) activity in human breast cancer tissue, human uterus (endometrium), and rabbit uterus. The optimum response was obtained with three different doses of IFN-alpha 10, 100, and 1000 U per ml. Escalation of the dose up to 5000 U per ml did not increase further ER activity. Cytosol fractions with zero or low binding activity (below 10 fm per mg) did not respond to IFN-alpha treatment. Addition of antibodies against IFN-alpha resulted in abrogation of IFN-alpha effect. Use of recombinant IFN-alpha or highly purified lymphoblastoid IFN-alpha showed similar effects on ER. The mechanism of the augmentation effect of ER activity by IFN-alpha is not clear. The increase of ER activity may have important clinical applications if the same is obtained in vivo.

Animals↗

Further studies on the carcinogenic-free interval following exposure in experimental esophageal tumorigenesis.

247 C57B1 male mice were killed after Diethylnitrosamine (DEN) treatment at various time intervals ranging from one day to nine months. The number of esophageal tumors was divided by the length of the resected esophagus (i.e. Tumor Index = TI). Animals treated for up to 2 months had a TI of 0.1. Since the histological examination of the esophagi in those animals revealed only normal histology, the conclusion drawn was that the TI of 0.1 was a methodological error in assessing esophageal tumors by transillumination. Three months' treatment with DEN resulted in a 9-fold increased TI and 6 months' treatment in a 69-fold increased TI. Other groups of animals treated with DEN for the same period of time were allowed to survive 7, 9 or 12 months without further treatment. Animals treated with DEN for 1 day but followed without further treatment for 7 months demonstrated a 3.5-fold increased TI. For animals treated with DEN for only 14 days, (TI 0.1) and followed for 7 months with a carcinogenic-free diet, a 7-fold TI was observed. For the group of animals treated for 3 months (TI 0.9) but allowed to survive to complete 7 months on a carcinogen-free diet, a 5-fold higher TI was recorded. DEN animals treated for 6 months (TI 6.9) but allowed to survive 3 additional months had a TI of 9.6. A similar TI, namely 9.7, was found when the carcinogen-free interval was prolonged for 6 more months. These results suggest that clones of esophageal cells are "programmed" for tumor growth at an early stage of DEN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Independent expression of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with carcinoma and sarcoma.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified in the sera of 100 patients with sarcoma, head and neck carcinoma, oesophageal carcinoma, mesothelioma and lung carcinoma. VEGF and bFGF levels were generally higher in the sera of the tumor patients compared to the sera of healthy control subjects. Interestingly, VEGF and bFGF levels were generally not elevated in the same sera (p < 0.01), and covariation of the VEGF and the bFGF levels was only rarely observed during progressive disease, arguing for actual independence of factors. Very high levels of VEGF (668 pg/ml, n = 12) were observed in patients with mesothelioma, whereas bFGF levels were not increased in these patients. Our data suggest that VEGF levels increase with tumor progression and may be a useful marker for clinical monitoring of sarcoma and carcinoma patients.

Adult↗