Kjell Grankvist
Umeå University, Medical Biosciences, Faculty Member
... BJORN E. SANDSTROM$, KJELL GRANKti IST§ and STEFAN L. MARKLUND§ Swedish Defence Research Establishment, S-901 82 Umea, Sweden ... 2. Materials and methods 2 .1 . Cell lines and culture conditions P31, a mesothelioma, and HT29, a colon... more
... BJORN E. SANDSTROM$, KJELL GRANKti IST§ and STEFAN L. MARKLUND§ Swedish Defence Research Establishment, S-901 82 Umea, Sweden ... 2. Materials and methods 2 .1 . Cell lines and culture conditions P31, a mesothelioma, and HT29, a colon carcinoma, both of ...
Research Interests:
The present study was conducted to investigate if chromosome band 3p14 is of any pathogenic significance in the malignant process of breast cancer. Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have... more
The present study was conducted to investigate if chromosome band 3p14 is of any pathogenic significance in the malignant process of breast cancer. Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have proposed LRIG1 at 3p14 as a candidate tumour suppressor. The LRIG1 gene encodes an integral membrane protein that counteracts signalling by receptor tyrosine kinases belonging to the ERBB family. LRIG1 mRNA and protein are expressed in many tissues, including breast tissue. In the present report we analysed the LRIG1 gene by fluorescence in situ hybridisation (FISH), LRIG1 mRNA by quantitative RT-PCR, and LRIG1 protein by western blot analysis. Two tumour series were analysed; one series consisted of 19 tumour samples collected between 1987 and 1995 and the other series consisted of 9 tumour samples with corresponding non-neoplastic breast tissues collected consecutively. The LRIG1 gene showed increased copy number in 11 out of 28 tumours (39%) and ...
Research Interests:
Research Interests:
Research Interests:
Somatic symptoms in the premenstrual syndrome (PMS) may have an etiology separate from that of the mental symptoms. A disturbance in mineralocorticoid action has been discussed, as mineralocorticoids regulate water balance.... more
Somatic symptoms in the premenstrual syndrome (PMS) may have an etiology separate from that of the mental symptoms. A disturbance in mineralocorticoid action has been discussed, as mineralocorticoids regulate water balance. Desoxycorticosterone (DOC) is interesting, as it has mineralocorticoid effects and is a precursor to the neurosteroid 5 alpha-pregnan-3 alpha,21-diol-20-one (THDOC). THDOC is a steroid with direct benzodiazepine-like effects on the GABA-A receptor in the brain that is metabolized from DOC within the brain and in the periphery. Ten women with PMS having swelling as a major symptom and eight controls were recruited. They marked, on a validated visual-analog scale, three physical symptoms every evening during one menstrual cycle in conjunction with giving blood samples for progesterone and DOC measurements. DOC showed menstrual cycle-linked variation correlating with progesterone. There was no difference in plasma DOC concentrations between patients and controls. The symptoms reached a maximum 1-3 days before the onset of menstruation, with a delay of 3-6 days after the hormone peak. DOC was less strongly correlated with the symptoms than progesterone. These results do not support the hypothesis that DOC is involved in the etiology of physical symptoms in PMS or that physical and mental symptoms have separate etiologies.
Research Interests:
Research Interests:
Research Interests:
Most errors in laboratory medicine occur in the preanalytical phase and are the result of human mistakes. This study investigated information search procedures, test request management and test tube labelling in primary healthcare... more
Most errors in laboratory medicine occur in the preanalytical phase and are the result of human mistakes. This study investigated information search procedures, test request management and test tube labelling in primary healthcare compared to the same procedures amongst clinical laboratory staff. A questionnaire was completed by 317 venous blood sampling staff in 70 primary healthcare centres and in two clinical laboratories (response rate = 94%). Correct procedures were not always followed. Only 60% of the primary healthcare staff reported that they always sought information in the updated, online laboratory manual. Only 12% reported that they always labelled the test tubes prior to drawing blood samples. No major differences between primary healthcare centres and clinical laboratories were found, except for test tube labelling, whereby the laboratory staff reported better practices. Re-education and access to documented routines were not clearly associated with better practices. The preanalytical procedure in the surveyed primary healthcare centres was associated with a risk of errors which could affect patient safety. To improve patient safety in laboratory testing, all healthcare providers should survey their preanalytical procedures and improve the total testing process with a systems perspective.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Refrigeration, Finland, Pregnancy, Humans, Female, and 9 moreHormones, Artifacts, Adult, Time Factors, ACTA, SERUM, Prenatal Care, Blood Proteins, and Cohort Studies(Hormones, Artifacts, Adult, Time Factors, ACTA, SERUM, Prenatal Care, Blood Proteins, and Cohort Studies)
(Hormones, Artifacts, Adult, Time Factors, ACTA, SERUM, Prenatal Care, Blood Proteins, and Cohort Studies)
Plasma testosterone, unbound testosterone, Sex Hormone Binding Globulin (SHBG) and albumin were studied in women with 'non-endocrine' ovarian carcinoma prior to and during chemotherapy. Fifty-one postmenopausal or... more
Plasma testosterone, unbound testosterone, Sex Hormone Binding Globulin (SHBG) and albumin were studied in women with 'non-endocrine' ovarian carcinoma prior to and during chemotherapy. Fifty-one postmenopausal or oophorectomized women with cancer of the ovary were studied. The histologic types were IC, IIC, IIIC, V and FIGO stages I-IV. Tumor volumes were evaluated once a month using bimanual recto-vaginal palpation under anesthesia. Blood samples were drawn for testosterone radio-immunoassay, SHBG and albumin analysis on four occasions at monthly intervals. Plasma levels were compared with a control group of postmenopausal women, a control group of fertile women in the follicular phase of the menstrual cycle, and finally a control group of postmenopausal women with non-gynecologic disseminated malignant disease. Testosterone concentrations were found to be higher in women with carcinoma of the ovary than in postmenopausal controls and showed a relationship to tumor volume. Histologic type and FIGO stage were found to be less closely related to plasma testosterone concentration. No significant change was found in the unbound testosterone fraction. SHBG concentrations were elevated in the Large-tumor group. Albumin concentrations were decreased in the Large-tumor group, advanced tumor stage group and in the control group with non-gynecologic disseminated malignant disease.
Research Interests:
IntroductionOvarian cancer has very few known modifiable risk factors but dietary studies suggest a role for vitamin D and calcium in the prevention of ovarian cancer. Thus, we investigated the association between pre-diagnostic serum... more
IntroductionOvarian cancer has very few known modifiable risk factors but dietary studies suggest a role for vitamin D and calcium in the prevention of ovarian cancer. Thus, we investigated the association between pre-diagnostic serum calcium and 25-hydroxyvitamin D (25-OHD) on the risk of later development of ovarian cancer.
Research Interests:
Research Interests:
Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone... more
Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% c...
Research Interests:
Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy... more
Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); P...
Research Interests: Cancer, Risk, Finland, Pregnancy, Humans, and 7 moreFemale, Young Adult, Risk factors, Middle Aged, Adult, Risk Factors, and Case Control Studies
Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens... more
Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP)...
Research Interests:
Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has been shown to be metabolised and to induce specific antiproliferative effects in malignant glioma, including arrest of glioma cells in the G2/M phase of the... more
Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has been shown to be metabolised and to induce specific antiproliferative effects in malignant glioma, including arrest of glioma cells in the G2/M phase of the cell cycle, damage to cell membranes and DNA and induction of free oxygen radicals. To evaluate further the effects of estramustine, an in vivo rat glioma model using inbred BD-IX rats and the BT4C cell line was set up. In order to detect cells with fragmented DNA, tumour and brain specimens were, following fixation for histological examination, processed for in situ end labelling (ISEL) with biotin-labelled nucleotides. Fresh tissue fragments were also used for DNA integrity analysis on agarose gels. It was demonstrated that estramustine induced clusters of ISEL-positive cells and a pronounced typical fragmentation of DNA 0.5-8 h after treatment. In tumours examined 24 or 94 h after estramustine treatment, and in untreated tumours, only occasional s...
Research Interests:
Four human cell lines derived from malignant gliomas were immunohistochemically examined for their content of estramustine-binding protein (EMBP). EMBP was detected in a large amount in all glioma cells during the entire cell cycle. EMBP... more
Four human cell lines derived from malignant gliomas were immunohistochemically examined for their content of estramustine-binding protein (EMBP). EMBP was detected in a large amount in all glioma cells during the entire cell cycle. EMBP has previously been demonstrated to be the major receptor protein in prostatic cancers for the cytostatic drug estramustine-phosphate (EMP). EMP caused a dose-dependent inhibition of exponentially growing cells by increasing the number of cells in G2/M stage of the cell cycle as monitored by flow cytofluorometry. The effect may be coupled to arrest of the glioma cells at metaphase. The presence of EMBP may suggest a selective binding and effect of EMP in glioma cells.
Research Interests: Cell Cycle, Prostate Cancer, Cell Division, Cell line, Humans, and 2 moreGlioma and Malignant Glioma(Glioma and Malignant Glioma)
(Glioma and Malignant Glioma)
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... more
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 fu...
Research Interests:
Research Interests:
Most mistakes in laboratory medicine are the result of human error occurring before the blood sample reaches the laboratory. This survey of preanalytical procedures was designed to identify sources of error and potential targets for... more
Most mistakes in laboratory medicine are the result of human error occurring before the blood sample reaches the laboratory. This survey of preanalytical procedures was designed to identify sources of error and potential targets for quality improvement strategies. The staff in a highly specialized surgical ward at a university hospital completed a questionnaire addressing the collection and handling of venous blood samples in plastic vacuum test-tubes for general clinical chemistry testing. The results suggest that venous blood sampling instructions are not always followed. When uncertain about how a sample should be collected, the majority of respondents rely on potentially poor sources of information, such as out-of-date printed instructions or the advice of a colleague, rather than consult up-to-date electronic instructions. Furthermore, they do not always report errors and the referrals are not always handled according to sampling instructions. The respondents were highly motivated, however, and had a strong interest in receiving further education in, and assuming increased responsibility for, venous blood sampling procedures in the ward. We believe that the introduction of standardized routines and regular staff training, combined with an exchange of the existing paper-based referral management system with an electronic system for managing referrals, could increase safety in the preanalytical process, with positive effects on patient safety. Given the importance of venous blood samples in patient care, a more extensive study covering other hospital wards and primary health-care centres is needed.
Research Interests:
Incident reporting is commonly used to improve patient safety. The preanalytical phase of laboratory testing contains several manual error-prone tasks where mistakes can affect patient outcomes. However, the practical use of incident... more
Incident reporting is commonly used to improve patient safety. The preanalytical phase of laboratory testing contains several manual error-prone tasks where mistakes can affect patient outcomes. However, the practical use of incident reports in this area has not been previously investigated in the primary health care setting, where the majority of the patients come in contact with health care. All staff responsible for venous blood sampling in 70 primary health care centres and in two hospital clinical laboratories (317 respondents, response rate 94%) completed a questionnaire. Of the primary health care staff, 69% reported that they had never filed an incident report regarding venous blood sampling. Barriers for not filing incident reports often/always included lack of time (44%) and a complicated reporting procedure (27%). A higher proportion of staff with re-education (43%) had filed at least one incident report as compared to those without re-education (20%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). No differences in incident reporting practices were found between primary health care and hospital clinical laboratory staff. The investigated incident reporting system is likely to underreport incidents in the preanalytical phase. Therefore, the ability to discover preventable system vulnerabilities needs refinement.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
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... more
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.
Research Interests:
Serum levels of three glycoprotein tumour antigens (carcino-embryonic antigen, CEA; cancer-associated antigen 50, CA-50; gastrointestinal cancer-associated antigen, CA 19-9) were determined on 125 consecutive patients with tumours of the... more
Serum levels of three glycoprotein tumour antigens (carcino-embryonic antigen, CEA; cancer-associated antigen 50, CA-50; gastrointestinal cancer-associated antigen, CA 19-9) were determined on 125 consecutive patients with tumours of the head and neck region. Elevated CEA values (greater than 5 units/ml) were found in 13/70 squamous cell carcinomas, 3/21 benign and 4/18 malignant salivary gland neoplasms. Elevated CA-50 values (greater than 17 units/ml) were found in 19/70 squamous cell carcinomas, 6/18 malignant and 1/21 benign salivary neoplasms. CA 19-9 displayed higher values (greater than 37 units/ml) in 9/68 squamous cell carcinomas, 4/18 malignant and none of 21 benign salivary gland tumours. Combination of CEA and CA-50 analyses increased the proportion of elevated values to 30/70 in squamous cell carcinomas and 10/18 in salivary gland malignancies. In squamous cell carcinomas no correlation between staging or grading and serum levels was detected for any of the markers. Among malignant salivary gland tumours, CA-50 displayed enhanced serum values in 4/6 mucoepidermoid carcinomas. The mean values for CA-50 and CA 19-9 serum levels were significantly higher for malignant salivary gland neoplasms compared to benign tumours. There was a close correlation between CA-50 and CA 19-9 serum levels. Although, the results suggest that at present none of the tumour markers tested have a place alone in the routine examination of patients with tumours affecting the head and neck region, further studies on salivary gland neoplasms and combinations of the tumour markers are justified.