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R Henriksson

Publications and source records attributed to R Henriksson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma.

PURPOSE: The prognostic value of vascular endothelial growth factor (VEGF) protein, known to stimulate endothelial growth and angiogenesis, was evaluated in node-negative breast carcinoma (NNBC) and compared with established prognostic factors. PATIENTS AND METHODS: In 525 consecutive patients with primary invasive NNBC (T1-2N0M0; tumor, node, metastasis stage), of whom 500 patients did not receive any systemic therapy, the cytosolic levels of VEGF165 were measured by using a quantitative enzyme-linked immunosorbent assay. The median follow-up was 46 months. Univariate and multivariate analyses were performed. RESULTS: VEGF level was significantly inversely correlated with estrogen receptor (ER) positivity but positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/microg of DNA) showed a significantly shorter survival time (P=.0012) than patients with levels less than the median value, also when analyzed as a continuous variable (P=.0277). Tumor size, grade, and ER expression were all statistically significant for overall survival in univariate analyses (P=.0069, P=.014, and P < .001, respectively). Multivariate analysis showed that VEGF level was the strongest predictor of overall survival (P=.0199). Histologic grade was also an independent predictor of survival (P=.0477). Among the 381 patients with ER-positive tumors, a group in general considered to have a good prognosis, we found a significant reduction in survival for those with levels of VEGF greater than the median value (P=.0009). CONCLUSION: The results suggest that the level of VEGF165 protein is an independent, strong prognostic factor for survival in patients with NNBC, especially in the subgroup of patients with ER positivity. Thus, cytosolic VEGF165 might be useful to select patients for adjuvant systemic therapy.

Adult↗
PubMed1998

Pharmacokinetics and pharmacodynamics of estramustine phosphate.

Estramustine phosphate (estramustine phosphate sodium), a carbamate ester combining 17 beta-estradiol and nor-nitrogen mustard, is a cytotoxic drug used in the treatment of advanced prostatic carcinoma. Because of the radiosensitising effect of this drug there has been a recent increase in interest concerning estramustine phosphate and its clinical use. It has also been found that the early recommendations of drug administration together with food or milk were inappropriate, since calcium containing food and antacids hamper drug uptake. This may have obscured results from earlier clinical studies with estramustine phosphate. Estramustine phosphate is currently being re-evaluated for the treatment of other tumours such as glioma and mammary carcinoma. This review summarises the present relatively limited knowledge concerning the pharmacokinetic and pharmacodynamic aspects of estramustine phosphate and its metabolites.

Animals↗
PubMed1998

Apoptotic tumor cell death induced by estramustine in patients with malignant glioma.

Estramustine phosphate (EMP), a cytotoxic drug used in the treatment of prostatic carcinoma, is metabolized and exerts specific cytotoxic effects in malignant glioma in vitro and in vivo. In the present study, we have evaluated the cytotoxic effect of EMP in the clinical situation with regard to appearance of DNA damage and its correlation to the uptake of estramustine (EaM) in human malignant astrocytoma tissue. Ten patients were given 280 mg of EMP p.o. 12 h before surgery. Specimens from brain tumor tissue were collected during surgery and used for detection of fragmented DNA, a hallmark of apoptosis, with in situ end labeling (ISEL) and agarose gel techniques. The main metabolite of EMP in glioma tissue, EaM, was analyzed with gas chromatography. It was demonstrated that EMP induced clusters of ISEL-positive tumor cells and fragmentation of DNA on agarose gels in patients treated with EMP. In the same patients, a significant uptake of EaM in tumor tissue was demonstrated. In control patients, who were not treated with EMP, and in two EMP-treated patients with no uptake of EaM, no signs of fragmented DNA and only a few scattered ISEL-positive cells were seen in the tumor tissue. Signs of apoptosis were also seen in two different experimental models, i.e., in vitro cell cultures of rat glioma cells and an in vivo rat glioma model. It is suggested that EaM can induce apoptosis by a direct effect on a subpopulation of glioma cells in human brain tumors in the clinical situation.

Adult↗
PubMed1997

VIP in the rat parotid gland in response to irradiation.

In the present study, the immunohistochemical expression of vasoactive intestinal polypeptide (VIP) in the parotid gland of rats exposed to fractionated irradiation was examined. VIP concentration was analyzed by radioimmunoassay (RIA). Irradiation lead to a marked increase in the immunohistochemical expression of VIP in the innervation of the gland parenchyme. VIP-like immunoreactivity (LI) frequently coexisted with SP (substance P)-LI in these nerve fibers. The pattern of VIP-innervation in association with large ducts and blood vessel walls was unchanged. RIA analysis revealed a more than three-fold elevation in VIP content in the gland in response to irradiation. The increase in VIP immunoreaction and VIP content was seen at examination ten days after cessation of a five-day treatment with a total dose of 30-40 Gray. The upregulation of VIP may be related to changes in the production of neurotrophic factors and to an increased demand for a potentiation of secretagogue effects of SP.

Animals↗
PubMed1997

Bombesin-like peptide is present in duct cells in salivary glands: studies on normal and irradiated animals.

Bombesin (BN) and its mammalian counterpart gastrin-releasing peptide act as neuroregulatory hormones and tissue-specific growth factors, and have been implicated as peripheral and central satiety-inducing agents. In the present study, the immunohistochemical expression of BN in submandibular, sublingual and parotid glands of rats was examined 10 days after 5 consecutive days with daily doses of 6-8 Gy irradiation. Radioimmunoassay (RIA) methods were also used. Immunoreactive granular structures were observed within duct cells of both controls and irradiated animals. In the parenchyma of irradiated animals, very few nerve fibres showing BN-like immunoreactivity were observed. The RIA analysis showed that the content of BN-like material significantly increased in submandibular and parotid glands in response to irradiation. The results suggest that mainly a non-neural form of BN is detected in the salivary glands in the immunohistochemical analysis. Thus, the immunohistochemical observations suggest that BN-like peptides may be present in the duct system, where they may be constituents of the saliva. The observations of an increase in BN content in response to irradiation are of interest as BN has mitogenic effects, may stimulate secretion and contributes to satiety.

Animals↗
PubMed1997

Effects of cisplatin and amphotericin B on DNA adduct formation and toxicity in malignant glioma and normal tissues in rat.

In an attempt to modify the cytotoxicity of cisplatin, amphotericin B (AmB) was given as pretreatment to BDIX rats with intracerebral BT4C glioma implants. Ten animals given AmB 5 mg/kg i.p. followed by cisplatin 5 mg/kg i.p. displayed massive haematuria within 24 h after treatment and died a few days later. The antitumoral effect could not, therefore, be evaluated. Histopathological examination of the kidneys showed extensive tubular necrosis. No signs of apoptotic cell death were found using in situ end labelling with biotin-labelled nucleotides or with DNA integrity analysis in agarose gel electrophoresis. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the distribution of cisplatin in brain tumour, normal brain and kidney. Addition of AmB to cisplatin caused increased adduct formation in kidneys, particularly in tubular cells. It seems plausible that the nephrotoxicity, at least in part, was mediated by increased levels of cisplatin-DNA adducts. Pretreatment with AmB did not have any obvious effect on the formation of adducts in the cerebral cortex. The adduct levels in the tumours from animals pretreated with AmB were not significantly increased compared with those treated with cisplatin only. Thus, addition of AmB to cisplatin caused excessive nephrotoxicity suggesting a decrease in the therapeutic ratio of cisplatin.

Amphotericin B↗
PubMed1997

Ultrastructural morphometry of parotid acinar cells following fractionated irradiation.

The aim of this study was to evaluate the long term effects on the ultrastructure of parotid glands after fractionated irradiation. The method implemented involved 5 x 6 Gy and 5 x 8 Gy, Monday to Friday 6 MV photons. By unilateral irradiation, the contralateral parotid gland served as a control. Although irradiation diminished the acinar cell density in light microscopic sections from 75 to 32% after 5 x 8 Gy of irradiation, ultrastructural morphometry could not detect any statistically significant differences in acinar cell size, nuclear size, nuclear density, granule area, mean granule size, or granule density. In general, greater differences were seen between rats receiving 30 or 40 Gy, on both the irradiated and the control size, than between the irradiated side and the control side. This was interpreted as due to differences in the nutritional state of the animals. This analysis concluded that individual acinar cells that survive irradiation seem not to be damaged in the long term when evaluated at the ultrastructural level. The study further stresses the importance of adequate sampling sizes and the use of adequate controls.

Analysis of Variance↗
PubMed1997

Computerized detection of morphological changes to glioma cells during estramustine and ion-channel blocker perifusion.

A perifusion technique for microscopy with computerized detection of early changes in cell morphology during continuous perifusion was used to show that the geometry of cultured glioma cells (MG-251) changes rapidly when they are exposed to estramustine phosphate (EMP). When the cells were exposed to 20 or 40 mg l(-1) EMP, cell volume projected cell area (PCA) rapidly increased. When the Na+,K+-ATPase blocker ouabain (100 micromol l(-1)) was added to the EMP (40 mg l(-1)) perifusion, the acute EMP response was eradicated. When the PCA curve for ouabain alone was subtracted from the curve of combined ouabain and EMP perifusion, the resulting curve showed that ouabain completely blocked the EMP-induced increase in PCA. When the Na+, K+, Cl- co-transport inhibitors bumetanide (10 micromol l(-1)), or furosemide (100 micromol l(-1)), were added to EMP (40 mg l(-1)), the acute increase in PCA seen for EMP alone was also completely blocked. This study shows that inhibitors of ion transmembrane transport can modify EMP-induced cell volume increases. This may be of particular importance since the blockers have been found to interfere also with the cytotoxic function of EMP during cell culture. Thus, it is possible that cell volume changes could serve as a rapid technique for predicting the cytotoxic activity of antineoplastic drugs.

Bumetanide↗
PubMed1997

Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.

OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed. METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated. RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight. CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

Animals↗
PubMed1997

Daily-diary evaluated side-effects of conformal versus conventional prostatic cancer radiotherapy technique.

Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients.

Abdominal Pain↗
PubMed1997

VEGF and tPA co-expressed in malignant glioma.

Neovascularisation and migration of tumour cells are two features of highly malignant glioma. Vascular endothelial growth factor (VEGF) and tissue plasminogen activator (tPA) seem to be of importance in the process of malignancy. In the present study a topographical co-expression of tPA mRNA and VEGF mRNA (VEGF121 and VEGF165 isoforms) was demonstrated in the tumour edge of a rat malignant glioma, using in situ hybridisation. No signs of co-expression was seen in the normal brain tissue. In the normal brain the forms of VEGF mainly expressed were VEGF121, VEGF165, and VEGF189. Further studies are required to show whether VEGF and tPA are produced by the same tumour cells and to elucidate the role of this co-expression.

Animals↗
PubMed1997

Rat salivary gland function after fractionated irradiation.

The aim of this study was to investigate longitudinal effects of fractionated irradiation, with various total doses, on salivary gland function in the rat. Female Sprague-Dawley rats were irradiated with 4, 5, 6, 7 or 8 Gy per day on five consecutive days. Irradiation was given to the head and neck region. Whole saliva was collected before and 2, 15 and 26 weeks after irradiation. In general the effects of irradiation on salivary gland function were found to be related to dose and time after exposure. Secretion rates were significantly decreased two weeks after irradiation with doses of 30 Gy or higher, after 15 weeks with 25 Gy or higher, and after 26 weeks with 20 Gy or higher. Response patterns to irradiation differed between the salivary constituents. Thus, the conclusions from this study are that early and late effects display different patterns and that the model used to study variations in salivary gland function after fractionated irradiation must be adjusted to the question addressed.

Animals↗
PubMed1996

Estramustine in malignant glioma.

Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas.

Animals↗
PubMed1996

The creation of protection and hope in patients with malignant brain tumours.

The malignant brain tumour disease condenses much of the anguish of cancer diseases. The brain is a vital and delicate organ, and the prognosis is generally unfavourable. The patient is exposed and has to rely on cognitive manoeuvres to manage the mental stress. The purpose of this study was to generate new insights into how the patient constructs a new sense of reality when confronted with the malignant brain tumour diagnosis. Within grounded theory methodology, 30 patients with malignant gliomas were interviewed twice, in direct connection with diagnosis, surgery and radiotherapy. In addition, their partners were interviewed, and quantitative instruments (SMMSE, RDCQ) were used as additional references for assessing the patients cognitively and emotionally. Eleven patients were excluded from the final analysis because of cognitive impairment of personality change. Most of the patients were aware of the fact that the brain tumour exposed them to grave danger, but they were also able to use various cognitive manoeuvres to create protection and hope. This process originated from different sources: the body; helpful relations; cognitive schemata; and the handling of information. The importance of the body to raise hope is emphasized. In the discussion we consider this process as an expression of how the patient brings together reality and hope, thus creating her/his own illusion. These findings are also related to adjacent psychoanalytic theory, proposing a theoretical reference with clinical implications when discussing "What to tell cancer patients."

Adaptation, Psychological↗
PubMed1996

A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy.

BACKGROUND: There are few randomised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy. The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo. MATERIALS AND METHODS: One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study. The patients recorded daily emesis, nausea and bowel habit and graded weekly symptoms of nausea, vomiting, diarrhoea and lack of appetite. The EORTC C30 questionnaire was completed. RESULTS: 67% of patients given ondansetron had complete control of emesis compared with 45% of patients with placebo (P < 0.05). The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group (P < 0.01). Patients given ondansetron had fewer days with emesis and nausea compared with placebo (P < 0.05). The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group (P < 0.05). This difference persisted during the first three weeks, but not thereafter. Similarly, some quality of life measures showed significant differences in favour of the ondansetron group. More patients (n = 13) withdrew due to lack of efficacy in the placebo group compared with patients (n = 8) in the ondansetron group. CONCLUSIONS: The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen.

Abdomen↗
PubMed1996

Antagonistic effect of amphotericin B on carboplatin antitumor activity in human osteosarcoma xenografts.

Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to potentiate the cytotoxic effect of different chemotherapeutic drugs in vivo and in vitro. The purpose of this study was to determine whether AmB could enhance the carboplatin antitumor activity in a human osteosarcoma xenograft model. Nude mice, bearing s.c. transplanted osteosarcoma xenografts, received i.p. an injection of AmB (5 mg/kg) 6 h prior to carboplatin (20 mg/kg) or each of the drugs separately. The effect of treatment was assessed by analyzing tumor growth delay and T/C ratio. Carboplatin clearly reduced tumor growth when administered alone. However, an unexpected interaction was seen where AmB significantly decreased the antitumor effect of carboplatin. The present results contradict some earlier in vitro studies and indicate the complexity of this interaction in vivo. Hence, it seems that interactive phenomena in one experimental model, and especially with regard to AmB, cannot be universally applied to all experimental situations.

Amphotericin B↗