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Biomedical subjects

K Grankvist

Publications and source records attributed to K Grankvist.

At least 55 records · Page 3Linked to original sources
PubMed1995

Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro.

At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, as far as we know, not been studied in this respect. In the present study, the effects of the 5-HT3 receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10(-5) mol/l) had no effect on the survival of irradiated cells. Granisetron (10(-5) mol/l) significantly potentiated cytotoxicity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10(-7) mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT3 receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment.

Animals↗
PubMed1995

Growth hormone deficiency impairs blood clotting and reduces factor VII coagulant activity in rat.

To investigate pituitary effects on the vitamin K-dependent coagulation factors, female rats were hypophysectomized (hypox) and treated with growth hormone (GH), cortisone, thyroxine, vitamin K, or saline. After 11 days of treatment, the prothrombin time, platelet count, and factors II, VII, IX, and X were determined. The prothrombin time was 52.9 +/- 1.2% for control rats and 39.1 +/- 0.8% for hypox rats (mean +/- SEM; p < 0.001). All factors decreased after hypophysectomy, reaching significance for factor VII (from 264 +/- 23% to 131 +/- 9%; p < 0.001) and factor IX (from 28.4 +/- 2.2% to 17.1 +/- 2.5%; p < 0.01) while the platelet count was unaffected. When hypox rats were treated with GH, the prothrombin time increased to 50.9 +/- 1.0% (p < 0.001) and factor VII to 299 +/- 10% (p < 0.001). Factor II, IX, and X were slightly increased after GH substitution but not after cortisone, thyroxine, or vitamin K treatment. To summarize, GH is of importance for normal hemostasis in the female rat.

Animals↗
PubMed1994

Identification of potassium flux pathways and their role in the cytotoxicity of estramustine in human malignant glioma, prostatic carcinoma and pulmonary carcinoma cell lines.

Clinically-used drugs such as furosemide, bumetanide and cardiac glycosides, are modulators of transmembrane fluxes of cations. Recently, it has been suggested that the regulation of intracellular cation concentrations could be a primary target for anti-neoplastic drugs, and that the cytotoxic activity may be altered by inhibitors of cation fluxes at the level of the plasma membrane. Therefore, we investigated the mechanisms by which cations are translocated across the plasma membrane of malignant glioma (U251 MG), prostatic carcinoma (PC3) and pulmonary carcinoma (P31) cell lines. The interactions between cation flux inhibitors and the cytotoxicity of estramustine were also evaluated. Ouabain, the classical inhibitor of Na+, K+ATPase, markedly reduced 86Rb (K+) influx in all three lines, indicating that this ion transport system is present in the cells. Furosemide and especially bumetanide inhibited the 86Rb influx, indicating the presence of the Na+, K+, Cl- co-transport system. The potassium channel blocker, tetraethylammonium, but not apamin reduced the influx of 86Rb showing that high conductance K+ channels are present, but that channels of low conductance probably do not exist in these cell lines. The Na+, K+, Cl- co-transport inhibitors furosemide and bumetanide significantly reduced cytotoxicity of estramustine in P31 cells, whereas no interaction between other K+ flux inhibitors and the anti-neoplastic drugs were detected in any of the cell lines investigated. Thus, the data show that Na+, K+, ATPase and NA+, K+, Cl- co-transport systems and K+ channels of high conductance are present in malignant glioma (U251 MG), prostatic carcinoma (PC3) and pulmonary carcinoma (P31) cell lines, and that inhibition of the Na+, K+, Cl- co-transport system in P31 is associated with reduced cytotoxicity of estramustine. The results justify further studies evaluating the role of these cation flux pathways in terms of targets for anti-neoplastic therapy.

Bumetanide↗
PubMed1994

Plasma prealbumin in women with epithelial ovarian carcinoma.

BACKGROUND: Epithelial ovarian carcinoma produces steroid hormones that may be of prognostic importance. The steroids are mainly bound to plasma albumin and sex hormone-binding globulin. Alterations in plasma protein levels influence hormonal effects. As plasma prealbumin may reflect changes in the patient's clinical status better than do albumin determinations, it is of interest to analyze prealbumin in patients with ovarian cancer. METHODS: Fifty-one postmenopausal or oophorectomized women with epithelial cancer of the ovary were studied. Plasma prealbumin was analyzed prior to and during chemotherapy. Tumor volumes were evaluated and blood samples were drawn for prealbumin analysis on four occasions at monthly intervals. Plasma levels were compared with one control group of postmenopausal women, one group of fertile women in the follicular phase of the menstrual cycle, and one control group of postmenopausal women with nongynecologic disseminated malignant disease. RESULTS: Prealbumin concentrations are lower in women with carcinoma of the ovary than in postmenopausal controls and the levels correlate inversely to tumor volume. Prealbumin concentrations are decreased in the large tumor group, advanced tumor stage group and in the control group with nongynecologic disseminated malignant disease. During chemotherapy, plasma prealbumin increases concomitantly with the reduction of tumor volume. Initial plasma prealbumin concentration seems to have prognostic importance. CONCLUSIONS: Prealbumin may be a sensitive indicator of disturbances in protein metabolism. It may reflect changes in the patient's clinical status better than do albumin determinations. Prealbumin concentration seems to have a prognostic importance in women with epithelial ovarian carcinoma. CONDENSATION: Prealbumin is studied in women with epithelial ovarian carcinoma prior to and during chemotherapy, and is found to vary inversely with changes in tumor volume.

Adult↗
PubMed1993

Serum gamma-enolase and prognosis of patients with renal cell carcinoma.

BACKGROUND: Increased levels of gamma-enolase (gamma-enolase) have been observed in the sera of patients with renal cell carcinoma. To evaluate the prognostic information of gamma-enolase in this disease, 161 consecutive patients were assessed before initiation of therapy. METHODS: gamma-Enolase was analyzed in serum using an immunoradiometric assay. The patients were clinically staged and followed up for a median time of 36 months (range, 5-104 months). Actuarial survival was calculated using the Kaplan-Meier method. RESULTS: Elevated levels of gamma-enolase was found in 28 of 61 (46%) patients with distant metastases, compared with 8 of 56 (14%) when the tumor was confined to the kidney. A correlation also was observed between gamma-enolase and tumor grade, with poorly differentiated tumors having the highest levels. In 28 patients with distant metastases and elevated gamma-enolase, the survival time was significantly shorter than that of 31 patients with normal gamma-enolase levels (P < 0.001). The median survival time was 5 and 11 months, respectively. Using Cox proportional hazard model, clinical stage, serum gamma-enolase, and tumor grade were identified as independent prognostic factors. CONCLUSION: Serum gamma-enolase can be useful as an adjunct in the staging of renal cell carcinoma. It also gives predictive information and might be of value as a marker in adjuvant therapy.

Adult↗
PubMed1992

Amiloride but not bumetanide protects against the cytotoxic effects of estramustine and bleomycin in cultured fibroblasts.

The effects of the clinically used diuretics amiloride (an inhibitor of Na+/H+ exchange) and bumetanide (an inhibitor of Na+, K+, Cl- co-transport) were tested on the cytotoxicity of estramustine and bleomycin in cultured fibroblasts. Both estramustine (50 micrograms/ml) and bleomycin (10 micrograms/ml) reduced the number of surviving clones. Amiloride (100 microM) but not bumetanide (100 microM) partly protected against the cytotoxic effect of both estramustine and bleomycin. The protective effect of the combination of amiloride and bumetanide was not stronger than the effect of amiloride alone. Amiloride or bumetanide alone did not affect the clonal survival. It is suggested that the protective effect of amiloride is not mediated by an effect of the molecular mechanism of cytotoxicity but may rather be due to changes in cellular metabolism and/or drug handling.

Amiloride↗
PubMed1992

Effects of clonidine-induced hypotension and dopamine-induced hypertension on blood flows in prostatic adenocarcinoma (Dunning R3327) and normal tissues.

In the present study it was investigated whether hypertension induced by dopamine or hypotension induced by clonidine could influence the relative blood distribution in a s.c. transplanted prostatic adenocarcinoma in relation to blood flow in normal tissues in rats. The blood flow was measured by using a radioactive microspheres technique. A bolus injection of 5 micrograms clonidine caused a decrease in the systemic blood pressure with 15-45 mm Hg, and blood flow to the central parts of the tumor, decreased with more than 50%. In the prostate, testes and ileo-psoas muscle a similar reaction was seen. During an infusion of 95-120 micrograms/kg/min dopamine, the blood pressure increased with 15-30 mm Hg, but the blood flow to the tumor was unchanged. However, in the testes and kidneys a decreased blood flow was observed. Moreover, mean blood flow to the central parts of the tumor decreased with increase in tumor size. The results further indicated that hyper- or hypotension or concomitantly given vasoactive drugs with the specific cancer treatment can have unwarranted effects on the distribution of cytotoxic drugs and oxygenation of the tumor.

Adenocarcinoma↗
PubMed1992

Erythropoietin in renal cell carcinoma: evaluation of its usefulness as a tumor marker.

Erythropoietin levels in serum were analyzed in 165 patients with renal cell carcinoma. All samples were taken before therapy and stored at -80 degrees C. Erythropoietin, a glucoprotein produced by the renal cortex was quantified by an enzyme immunoassay. Fifty-five of 165 patients (33%) had elevated serum levels. In patients with metastatic disease (M+), elevated levels were found in 24 of 65 cases (38%). Patients with high-grade tumors had significantly more often increased erythropoietin than those with low-grade tumors. No correlation between erythrocytosis and elevation of erythropoietin in serum was found. There was a significant difference in survival between patients with normal and patients with elevated erythropoietin levels (p = 0.013). The study shows that erythropoietin is a tumor marker with a low sensitivity. However, it correlates with stage and grade and provides prognostic information.

Biomarkers, Tumor↗
PubMed1992

Chlorpromazine enhancement of epirubicin cytotoxicity in vitro: effects on plasma membrane and DNA damage.

The frequently used antiemetic drug chlorpromazine has previously been shown to augment anthracycline-induced toxicity to cultured Chinese hamster fibroblasts measured by cloning /1/. We therefore tested the ability of chlorpromazine to affect the induction of plasma membrane and DNA damage by the anthracycline epirubicin. Plasma membrane damage was determined by the cells' ability to accumulate 86Rb after incubation with 10 mg/l epirubicin, and DNA damage was determined by measuring the amount of DNA precipitation after incubation with 25 mg/l epirubicin. The epirubicin-induced inhibition of 86Rb-accumulation as well as the enhancement of epirubicin-induced DNA damage were markedly enhanced in the presence of chlorpromazine. Chlorpromazine augmentation of epirubicin cytotoxicity, including plasma membrane and DNA damage, may be due to its calmodulin antagonistic action and related to the maintenance integrity. Further studies are justified to evaluate the effects of chlorpromazine influence on antineoplastic drug action in vitro and in vivo.

Animals↗
PubMed1991

Serum dehydroepiandrosterone sulfate in Alzheimer's disease and in multi-infarct dementia.

Circulating levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol were studied in 86 patients with dementia; 45 with Alzheimer's disease and 41 with multi-infarct dementia. Compared to an elderly control group, after adjustment for age and sex, patients with Alzheimer's disease were found to have lower serum levels of DHEAS. We found a covariation between serum albumin and DHEAS levels, which may be of importance regarding peripheral hormone concentration in patients with dementia. These findings may provide evidence for a role of DHEAS in amnestic disorder in humans, either reflecting or contributing to the course of dementing diseases.

Aged↗
PubMed1991

Interaction between cytostatics and nutrients.

Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The presence of the tumor alone may lead to reduced intake of different nutrients and treatment modalities such as surgery, chemotherapy and radiation therapy may further exacerbate nutritional disturbances. Dietary manipulation in experimental systems has shown improvement of tumor response to cancer therapy. Drug pharmacokinetics has been shown to be altered by changes in nutritional delivery. This article reviews the present knowledge, from experimental and clinical standpoints, of the potential role of different nutritional factors on the specific cancer treatment. It is obvious that alteration of at least some dietary factors affect the outcome of different forms of cancer treatment. Indeed, although interest in the clinical significance of optimal dietary intake and supplementation during cancer therapy so far remain marginal, accumulating data indicate that this area deserves further research attention.

Antineoplastic Agents↗
PubMed1991

Catecholamine excretion in old age.

Catecholamine excretion was studied in two groups of nonhospitalized subjects, 60 and 80 years of age, N = 35 and 29, respectively. Urinary 24h dopamine excretion exhibited an age-related decline (p = 0.001). There was a sex difference for dopamine excretion; men had higher excretion levels (p = 0.04). Twenty-four-hour excretion of epinephrine and norepinephrine was slightly higher in 60- than in 80-year-old individuals (NS). Smoking was associated with a considerable increase in epinephrine (p = 0.001) and norepinephrine (p = 0.04) excretion. Body mass index was negatively correlated to epinephrine excretion (r = -0.27; p less than 0.05). When analyzed with a multi-way analysis of variance with analysis of covariance, significant influences of age on dopamine excretion, of creatinine clearance on dopamine and norepinephrine excretion, and of smoking on epinephrine excretion were seen. Thus, factors such as age, gender, body mass, kidney function and smoking habits considerably influence catecholamine excretion in elderly people.

Aged↗
PubMed1991

Early morphological detection of estramustine cytotoxicity measured as alteration in cell size and shape by a new technique of microperifusion.

The present study describes a new microscopic perifusion technique for detecting momentary alterations in cell volume and shape. The method has been applied for evaluating early signs of cytotoxicity following chemotherapeutic treatments. The effects of estramustine phosphate (EMP) have been evaluated. EMP is a complex between oestradiol-17 beta and the alkylating agent nor-nitrogen mustard and has recently demonstrated a marked cytotoxicity against malignant glioma cells. The results showed a concentration-dependent increase in cell size and a concomitant decrease in shape factor following EMP-treatment of glioma cells. These changes correlated with cytotoxicity evaluated as cell proliferation and cell membrane alterations shown by 86Rb fluxes and ultrastructural visible membrane damage. The colon cancer line HT-29 displayed no reactions at all following EMP treatment. It is suggested that acute alterations in cell morphology and shape display a strong correlation to the cytotoxicity of EMP encountered by traditional cell culture systems. The findings are discussed with respect to cell membrane disturbances caused by EMP and its potential role as an early test of cytotoxicity.

Cell Line↗
PubMed1991

Assessment of hypothalamic-pituitary function in patients with familial amyloidotic polyneuropathy.

This study was performed to evaluate hypothalamic-pituitary hormone regulation in patients with familial amyloidotic polyneuropathy. Twenty-two patients without clinically overt endocrinological dysfunction were studied. A thyrotropin-releasing hormone test revealed abnormal growth hormone regulation in 9 of 17 (53%) patients, and abnormal prolactin regulation in 9 of 18 (50%) patients. Abnormalities in either growth hormone or prolactin regulation were found in 12 of 17 (71%) patients. Serum somatomedin C levels were normal in all 22 patients. In 3 of 18 (17%) patients the plasma arginine vasopressin levels were low relative to the serum osmolality levels. Thus abnormalities in hypothalamic-pituitary hormone regulation may be common in familial amyloidotic polyneuropathy.

Amyloidosis↗
PubMed1991

Effects of estramustine on DNA and cell membrane in malignant glioma cells.

Estramustine phosphate (EMP), a complex between estradiol-17 beta and nor-nitrogen mustard, commonly used in treatment of prostatic cancer, also exerts marked antiproliferative effects on cultured human malignant glioma cells. The mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically via the mitotic spindle, and related to the intact estramustine complex. EMP cytotoxicity was studied on the malignant glioma cell line U-251 MG. A dose-dependent increase in DNA strand breaks was demonstrated at EMP-concentrations ranging 10-40 mg/l. The uptake of 86Rb, used as a tracer for potassium to study ion transport and membrane permeability, was reduced after incubation with EMP. The mean decline in 86Rb accumulation by U-251 MG cells was 12, 20 and 32% at EMP concentrations 10, 20 and 40 mg/l respectively. Scanning electron microscopy gave further evidence for cell membrane damage. In conclusion, EMP seems to affect malignant glioma cells on several vital functions and the results indicate the the cytotoxic potential may at least partially be related to effects on DNA and cell membrane.

Cell Membrane↗
PubMed1991

Estramustine binding protein in human brain-tumor tissue.

Estramustine, an estradiol-17 beta and nornitrogen mustard complex, is used in the treatment of advanced prostatic carcinoma. A specific estramustine binding protein (EMBP) is important for its cytotoxic action, and the presence of EMBP has previously been demonstrated in rat and human prostatic cancer tissue. Significant levels of EMBP were detected by radioimmunoassay in human brain-tumor tissue. The EMBP concentrations (expressed as ng/mg protein) in 16 astrocytomas (mean 2.6 ng/mg, range 0.5 to 6.2 ng/mg) and seven meningiomas (mean 5.1 ng/mg, range 0.3 to 9.3 ng/mg) were significantly higher than that found in four samples of epileptic brain (mean 0.7 ng/mg, range 0.5 to 1 ng/mg) and 18 samples of normal brain (mean 0.5 ng/mg, range 0.2 to 1.0 ng/mg). The uptake, metabolism, and antiproliferative effects of the prostatic anticancer agent estramustine have been previously demonstrated in cultured glioma cells. The presence of EMBP may suggest a selective binding and effectiveness in human brain-tumor tissue.

Astrocytoma↗
PubMed1991

Plasma and urinary amino acids as indicators of proximal tubular function in primary hyperparathyroidism.

Nineteen patients with histologically confirmed parathyroid adenomas were studied immediately before and 12 months after operation. The concentrations of 37 amino acids were estimated by chromatography in plasma and urine. In addition, proximal tubular function was studied by measuring the excretion of beta 2-microglobulin. No general aminoaciduria was registered either before or after operation but there were variations between preoperative and postoperative values in the plasma and urinary concentrations of a few amino acids. There were no correlations between preoperative and postoperative concentrations of calcium, parathyroid hormone or the various amino acids in plasma or urine. Nor was there any between the fall in serum calcium and the concentrations of the amino acids. There was no correlation between glomerular filtration rate and the amount of the different amino acids filtered. beta 2-Microglobulin excretion was normal both before and after operation in all but one patient. Aminoaciduria does not seem to be present in primary hyper-parathyroidism. Plasma and urinary concentrations of amino acids were unchanged after parathyroidectomy and proximal tubular function, assessed by measuring concentrations of amino acids in plasma and urine and urinary excretion of beta 2-microglobulin does not seem to be affected in primary hyperparathyroidism.

Adult↗