New 17 beta-hydroxysteroid dehydrogenases. Molecular and cell biology of the type IV porcine and human enzymes.
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17-Hydroxysteroid Dehydrogenases↗
Biomedical subjects
J Carstensen
Publications and source records attributed to J Carstensen.
Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma.
DNA ploidy and S-phase fraction were measured by flow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases only the primary tumours or the last metastases could be evaluated. There was a significantly higher mean S-phase value in melanoma metastases from patients with complete or partial responses compared with patients with progressive disease. Neither the S-phase fraction of the primary tumour, nor the DNA ploidy of the primary tumour or of the last histologically verified metastases taken before inclusion into the study were associated with therapeutic response. In the multivariate analysis, both the anatomical location of the metastases and the S-phase fraction measured on the last metastases remained significant prognostic factors of response. In the univariate survival analysis, there was an association between high S-phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S-phase fraction, the number of involved metastatic sites and the treatment response were independent predictive factors. We conclude that, in disseminated melanoma treated with chemotherapy, a high S-phase fraction measured in the last histologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S-phase measurement as a potential tool for selecting patients for treatment.
Adolescent↗
DNA ploidy and S-phase in recurrent astrocytomas: a retrospective study by flow cytometry of deparaffinized specimens.
Twenty-two patients with recurrent astrocytic tumors were treated surgically two or even three times. At the time of the first surgery 6 tumors were fibrillary astrocytomas (grade II), 9 anaplastic astrocytomas (grade III) and 7 glioblastomas (grade IV). Histopathological specimens from second surgery demonstrated in 12 cases signs of higher grades of malignancy. Flow cytometry (FCM) did not reveal any significant changes of S-phase fraction (p = 0.55). This study supports the theory that, given enough time, the histopathology of brain tumors change significantly from more benign forms to more malignant ones. The flow cytometry (FCM) could trace a weak tendency to higher S-phase fractions at the time of the second surgery. No apparent change of ploidy pattern was observed. In spite of the unequivocal histopathological changes of the recurrent astrocytomas the flow cytometry failed to indicate similar changes in terms of ploidy and S-phase fraction parameters.
Adult↗
Soft tissue sarcoma after treatment for breast cancer.
In a register study all women in the West of Sweden Health Care Region with a breast cancer diagnosed between 1960 and 1980 (n = 13,490) were followed up in the Swedish Cancer Register to the end of 1988 for later occurrence of a soft tissue sarcoma (STS). Nineteen sarcomas were reported, whereas 8.7 were expected and the relative risk (RR) was 2.2 (CI 95% 1.3-3.4). The absolute risk was 1.7/10(4) person years (PY) in comparison with 0.8 expected. To obtain a more detailed analysis of the associations between arm lymphoedema, radiotherapy and STS development, and to control the quality of the register data, a case control study was also performed. Clinical records from the different hospitals in the region were collected for all the 19 cases as well as for three selected controls per case. The histopathology of the cases were reviewed, and one of the cases was reclassified as a malignant melanoma and excluded from further analysis. Thirteen of the cases were clustered around the treated breast area. To quantify the exposure to radiotherapy, the integral dose was estimated. The presence of lymphedema was included as a binary variable in the analysis. The exact conditional randomisation test indicated a significant correlation between the integral dose and the development of an STS (p = 0.008) and this association was still significant after stratification for arm oedema. A conditional logistic regression analysis with STS as the dependent variable and the integral dose as the explanatory variable gave an odds ratio (OR) of 5.2/100 J (CI 95% 1.3-21.2), and if this regression was restricted only to the STS developing in the radiation fields the OR was 3.2/100 J (CI 95% 0.8-12.9). Thus, the excess of STS in this breast cancer cohort was very low (0.9/10(4) PY). However the integral dose correlates well to the development of STS and can be useful in quantifying even small risks of secondary malignancies in the breast cancer population.
Arm↗
Correlations of Ki-67 and PCNA to DNA ploidy, S-phase fraction and survival in uveal melanoma.
In 79 patients with uveal melanoma, the tumours were investigated by DNA flow cytometry and immunohistochemical staining of PCNA and Ki-67. S-phase as a continuous variable was significantly correlated with Ki-67 (P = 0.033), but not with PCNA. DNA ploidy was not correlated with either of the two antigens. Ki-67 was significantly correlated with histopathological type (P < 0.001) and tumour size (P < 0.001). Large tumours and epithelioid cell type were associated with a high frequency of Ki-67 positive cells. A high level of Ki-67 positivity (> or = 6.5%) was also associated with a shorter survival (P = 0.0037), and when adjusted for DNA ploidy, histopathological type and tumour size, Ki-67 in the multivariate analysis remained an important prognostic factor (P = 0.017).
Antigens, Neoplasm↗
Impact of pregnancy on gender differences in sickness absence.
UNLABELLED: Women in general have a higher sickness absence than men, and sickness absence is particularly high among pregnant women. STUDY OBJECTIVES: To study the level of male sickness absence as compared to female, including and excluding pregnant women. DESIGN: Studies of incidence and length of sickness absence exceeding 7 days using population-based sick-leave records. SETTING: The community of Linköping, Sweden, 117,000 inhabitants. PARTICIPANTS: Subjects included in the analysis were all men and women aged 16-44 who in 1985 or 1986 had at least one sick-leave spell exceeding 7 days. RESULTS: Pregnant women had a very high sickness absence. When pregnant women were excluded, the female sick-leave rate decreased from 0.18 (95% C.I. 0.17-0.18) to 0.15 (95% C.I. 0.15-0.16) for all women. The corresponding male sick-leave rate was 0.12 (95% c.i. 0.12-0.13). Gender differences in length of sickness absence decreased to the same extent. The results were similar when restricting the analysis to employed persons. The decrease varied a little with occupational group and was largest in the age-group 25-34. CONCLUSIONS: When pregnant women were excluded the excess female sick-leave rate was halved, but still remained 25% higher than the male. The impact of excluding pregnant women was highest in the age group 25-34, where the fertility-rate was highest. Although only 5% of all women aged 16-44 were pregnant, they had a large impact on gender differences in sickness absence.
Absenteeism↗
Prognostic value of flow cytometry and correlation to some conventional prognostic factors: a retrospective study of archival specimens of 134 astrocytomas.
The S-phase fraction and the DNA ploidy type in 134 astrocytomas (18 Grade II, 46 Grade III, and 70 Grade IV astrocytomas) were studied using flow cytometry in a retrospective study of archival tumor specimens. A high grade of malignancy was associated with both a high S-phase fraction (p < 0.0001) and an aneuploid DNA pattern (p < 0.0001). There was no aneuploid DNA pattern found in the fibrillary astrocytomas (World Health Organization (WHO) Grade II); where-as the aneuploid pattern was observed in 80% of all the glioblastomas multiforme (WHO Grade IV). The age and gender of the patients were not significantly related to the flow cytometry parameters. The survival of patients with Grade II or III astrocytomas was significantly longer when their tumors exhibited a tetraploid DNA pattern or had a low S-phase fraction. In patients with Grade IV tumors, there was no correlation between length of survival and either the DNA ploidy or the S-phase fraction. In a multivariate Cox regression analysis of data obtained in patients with Grade II and III astrocytomas, age, grade of malignancy, DNA ploidy, and S-phase fraction were independent prognostic factors.
Adult↗
Adult cancer risks among the mothers of children with cancer.
We investigated cancer risk among mothers of 2365 children who were diagnosed with cancer between 1973 and 1989 in Sweden. From the date of birth of the child until 31 December 1989, 38 cases of cancer were diagnosed among the mothers. The expected number of cases, according to national rates, was 30.9. Cancer of the thyroid was the only site showing a significantly increased risk among the mothers (observed = 6, expected = 1.2, P < 0.01), but two cases were medullary cancer associated with an inheritable syndrome, and inherited by their children.
Adult↗
The tissue distribution of porcine 17 beta-estradiol dehydrogenase and its induction by progesterone.
Porcine 17 beta-estradiol dehydrogenase (EDH) was recently purified and cloned. It catalyzes the NAD(+)-dependent oxidation of estradiol to estrone 360-fold more efficiently than the back reaction with NADPH. The 32 kDa EDH is cut from an 80 kDa primary translation product with a multidomain structure unknown for other hydroxysteroid dehydrogenases. The highest EDH activities and strongest immunoreactions are found in liver (hepatocytes) and kidney (proximal tubuli) followed by uterus (luminal and glandular epithelium), lung (bronchial epithelium). Progesterone treatment of ovariectomized gilts stimulates oxidative EDH activity in uterus, anterior pituitary, skeletal muscle (diaphragm) and kidney. Constitutive levels of EDH activity were seen in the adrenals, the lung and the liver.
Animals↗
DNA ploidy and S-phase fraction as prognostic factors in patients with uveal melanomas.
In 96 patients with uveal malignant melanomas the tumours were investigated by DNA flow cytometry. Thirty-eight per cent of the melanomas were aneuploid. By univariate analysis significant correlations with survival were found for histological type, tumour size, DNA ploidy, evidence of 'blind eye' and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be histological type (P = 0.0008), tumour size (P < 0.0001) and DNA ploidy (P = 0.0038). Evidence of 'blind eye' was not significantly correlated with survival after adjustments for the other variables mentioned above. The S-phase fraction could be estimated in all 60 diploid tumours and in 12 of 36 aneuploid melanomas. By univariate analysis this variable was found to be a significant prognostic factor, but did not remain so after adjustment for ploidy, histological type and tumor size. We further conclude that patients with small DNA diploid uveal melanomas of spindle cell type have a rather favourable prognosis.
Adult↗
Myelofibrosis and benzene exposure.
Petrol station attendants are exposed to benzene, a well-known carcinogen for blood malignancies. A case of myelofibrosis in a petrol station attendant is presented, along with other reports of myelofibrosis after benzene exposure obtained from the Swedish Cancer Environment Register. Findings of an increased risk for myelofibrosis in the transport sector also suggest a causal relationship with benzene.
Benzene↗
p53 expression and the result of adjuvant therapy of breast cancer.
Functional p53 protein is essential for the cellular response to drug-induced DNA damage. We investigated p53 accumulation in tumour specimens from premenopausal breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal accumulation as judged with immunohistochemistry (> 10% positive tumour cells). The risk of distant recurrence was similar in the two treatment groups for patients whose primary tumours lacked p53 accumulation, whereas there was a significant benefit from CMF for patients showing abnormal accumulation (relative risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis is not a general mechanism by which breast cancer cells respond during CMF chemotherapy.
Aneuploidy↗
Pregnancy-related sickness absence among employed women in a Swedish county.
OBJECTIVES: The objective of this study was to analyze the variation of pregnancy-related sickness absence among employed women according to age, occupation, and degree of male-female domination within occupations. METHODS: Data from a prospective study of all new sick-leave spells exceeding 7 d in 1985 and 1986 in the county of Ostergötland, Sweden, were related to the population at risk, through the Swedish Medical Birth Register. The subjects included in the analysis were all 7000 employed women that gave birth in 1985 and 1986, of which some 3000 were sick-listed at least once with pregnancy-related diagnoses. RESULTS: There was little difference in the pregnancy-related sickness absence between the age groups. The age-standardized rate for sick leaves involving pregnancy-related diagnoses differed substantially between occupations. Women in the metal industry had the highest rates; those employed in administration, banking, and insurance had the lowest. White-collar occupations generally had lower rates and blue-collar occupations higher rates, with some exceptions (eg, in saw mills, farming, and the chemical industry). Gender-integrated occupations had the lowest sick-leave rate, while extremely male-dominated jobs had the highest. The latter association remained after adjustment for occupational area. CONCLUSIONS: There were considerable differences between occupational groups in the rates of sick leaves involving pregnancy-related diagnoses. Some differences were related to physical load of the jobs being done, but not all. It seems important to consider also male-female domination within a job with respect to such sick leaves.
Absenteeism↗
Prognostic factors in thin cutaneous malignant melanoma.
BACKGROUND: Thin melanomas can metastasize and be lethal. The predictive importance of tumor thickness in thin melanomas and the specific features identifying the patients at risk have not been investigated fully. METHODS: Prognostic factors were analyzed in 585 patients with clinical Stage I invasive cutaneous malignant melanoma with a thickness of less than or equal to 0.8 mm. The patients were included in a population-based cancer registry in Stockholm county during 1976-1987. They constituted about 64% of all patients with thin melanomas who were diagnosed in the region during the study period. Information was available on age, sex, anatomic site of the tumor, histologic type of melanoma, level of invasion, tumor thickness, and tumor regression. In a Cox regression analysis, the prognostic importance of each factor was studied. By a case-control technique with individual matching for the identified independent predictors of recurrence, the additional prognostic information given by type and grade of inflammatory response, presence of vertical growth phase, mitotic rate/mm2, and histologic ulceration of the tumor was assessed. RESULTS: After a median follow-up time of 50 months, recurrent disease developed in 26 patients (4%). There was no difference in recurrence rate between patients treated with narrow (1-2 cm) or wide (5 cm) excision. Anatomic site, tumor thickness, level of invasion, and tumor regression were found to be independent prognostic factors in the multivariate analysis. In the case-control study, only grade of inflammatory reaction added significant prognostic information. No subgroup could be identified that was without risk of recurrent disease. CONCLUSIONS: Thin melanomas do not seem to constitute a separate form of melanoma, but compose one end of a continuous spectrum of biologic behavior.
Adolescent↗
Experience with implanted subcutaneous ports for intraperitoneal chemotherapy in ovarian cancer.
Peritoneal access devices (port-catheters) were subcutaneously implanted in 125 patients for intraperitoneal chemotherapy of ovarian cancer. In 98% of patients Pharmacia's Port-A-Cath was used. Four hundred sixty-five intraperitoneal courses were given to these patients, with a median of 4 courses per patient (range 0-8). The first course was given 0-60 days (median 11 days) after Port-A-Cath implantation. In 125 patients, 27 (21.6%) complications of severe or moderate degree during the treatment were registered. In 81% of the patients, the treatment was given according to chemotherapy protocol as outlined. In 7% of the patients, early termination was related to the use of Port-A-Cath and in 12% related to chemotherapy. The probability for proper functioning of Port-A-Cath was 0.74 at 6 months and 0.69 at 1 year after implantation. The mean observation time was 13.6 months, median 10.5 (range 0.3-59.6 months). Total patient access time was 141.9 years. In conclusion, the complication rate after implantation of intraperitoneal access devices is acceptable. The rate of infections associated with the system is lower than that associated with open catheter systems.
Adult↗
S-phase determination of immunoselected cytokeratin-containing breast cancer cells improves the prediction of recurrence.
Estimation of S-phase fraction in breast carcinomas with single parameter flow cytometry may include errors due to dilution of cancer cells by host cells. Use of tissue specific markers may to some extent correct for the effect of dilution. S-phase fraction was estimated by flow cytometry with and without immunoselection in 80 DNA-euploid breast carcinomas in stage I-II. The tumor tissue was mechanically disintegrated and fixed in ethanol. A primary antibody, specific for cytokeratins 8 and 18, was added before incubation with the secondary FITC-conjugated antibody. S-phase fraction was calculated for both the gated (cytokeratin-positive) and the ungated cell population. An increasing proportion of tetraploid cells compared to diploid cells was found when the immunoselection method was used. The gated population tended to have a higher S-phase fraction than the ungated population. In univariate analysis S-phase fraction estimated from both ungated and gated cell populations yielded significant information for predicting recurrence when stratified for tumor size and nodal status. In bivariate analysis S-phase fraction of the gated population contributed prognostic information in addition to S-phase fraction of the ungated population when both variables were included in the analysis. Our conclusion is that S-phase fraction calculated from cytokeratin-positive cells provides prognostic information in addition to ungated S-phase values in DNA euploid breast carcinomas.
Biomarkers, Tumor↗
Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancer.
The p53 gene product is a tumour suppressor protein, and alterations of the protein are common in human cancer. Previous studies have focused on nuclear accumulation of p53. To investigate if cytoplasmic accumulation of p53 strengthens the relationships to different pathobiological variables and distant recurrence-free survival in breast cancer, tumours from 164 stage II patients were examined with the monoclonal antibody PAb1801. Nine per cent of the tumours were nuclear positive and 21% were cytoplasmic positive. Cellular p53 accumulation, related to the nucleus or the cytoplasm or both, showed stronger associations with pathobiological variables than nuclear accumulation alone. Accumulation of p53 was significantly correlated to tumour size over 20 mm, negative oestrogen receptor (ER) status, DNA aneuploidy, high S-phase fraction and positive erbB-2 status. Cytoplasmic p53 was significantly correlated to distance recurrence-free survival in patients negative for nuclear p53 (P < 0.0001). Cellular p53 accumulation was an independent prognostic factor, in addition to lymph node status and ER content. We conclude that consideration of cytoplasmic staining enhances the clinical importance of p53.
Breast Neoplasms↗
Deferred treatment of clinically localized low grade prostate cancer: the experience from a prospective series at the Karolinska Hospital.
From 1978 to 1982, 172 patients with stages T1 to 3NxM0 prostate cancer were included in a surveillance protocol with deferred treatment on symptomatic progression. Median patient age at diagnosis was 68 years (range 38 to 89 years). Mean followup was 80 +/- 32 months. Of the patients 58% had local and 19% had distant progression, and 52% had received treatment at followup. Disease specific survival rate at 10 years was 80% for the total series, 84% for the subgroup with stage T1 or T2 tumor and 92% for those with stage T1 or T2 tumor who were less than 70 years old at diagnosis. For the subgroup with stage T3 tumor the disease specific survival rate at 9 years was 70%. In all subgroups the competing mortality rate was higher than the prostate cancer mortality rate. Deferred treatment appears to be an acceptable option for patients with tumor clinically confined to the prostate and a life expectancy of 10 years or less.
Acid Phosphatase↗