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H Nordgren

Publications and source records attributed to H Nordgren.

At least 37 records · Page 2Linked to original sources

p53 immunoreactivity as prognostic marker for cancer-specific survival in prostate cancer.

OBJECTIVES: The objective of this study was to evaluate the role of p53 immunoreactivity as a prognostic marker in prostate cancer. METHODS: The nuclear accumulation of the aberrant p53 protein was determined by immunohisto-chemistry on surgical specimens and related to stage, grade and cancer-specific survival in 186 prostate cancer patients treated with transurethral resection and subsequent surveillance. RESULTS: There was a significant correlation between p53 staining and grade: 2% of the highly differentiated, 8% of intermediately, and 21% of the poorly differentiated tumors stained. Patients with p53-positive tumors had a significantly shorter survival (52 months) than the p53-negative group (123 months). However, in a Cox multiple regression analysis of p53 status, tumor stage, grade, metastasis and age, p53 lost its significance as an independent predictor. CONCLUSIONS: p53 is a rare and late event in prostate cancer, indicating that other molecular mechanisms may be of greater importance in the development of prostate cancer. The predictive value of p53 apparently depends on its association with high grade and advanced stage, and it is not a useful prognostic marker in prostate cancer. However, p53 status could play a role in the evaluation of patients prior to radiotherapy since p53 inactivation may produce radioresistant tumors.

Adult↗

Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53.

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.

Apoptosis↗

Estramustine-binding protein (EMBP) in renal cell carcinoma immunohistochemistry, immunoscintigraphy and in vitro estramustine effects.

The present report shows that the human renal cell carcinoma (RCC) cell lines, A498 and CAKI-2, express the estramustine-binding protein (EMBP). The RCC cell lines investigated were highly sensitive for estramustine, with cell arrest in atypical metaphase. In vitro experiments using a fluorimetric cytotoxicity assay (FMCA) showed a pronounced cytotoxic effect mediated by estramustine. Immunohistochemical analysis of tumour specimens from patients with RCC showed positive staining for EMBP in 12/16 cases. Immunoscintigraphy was performed in an experimental system in nude mice, heterotransplanted with the CAKI-2 cell line. A radiolabelled monoclonal anti-EMBP antibody was used. The results show a specific uptake of the antibody in the RCC tumour, expressed as a percentage of the injected dose per gram tissue, which ranged from 4.03 to 6.9. The results obtained form the basis for clinical studies on the feasibility of utilizing estramustine in the management of RCC. Immunoscintigraphy using the monoclonal anti-EMBP antibody is of potential use for in vivo characterization of the malignancy and in the selection patients suitable for treatment with estramustine.

Adult↗

Blood pressure response to physical exercise in healthy adolescents and adolescents with insulin-dependent diabetes mellitus.

1. Reference values for systolic blood pressure during exercise are provided for 88 healthy adolescents (12-22 years of age) of both sexes. Data were related to oxygen uptake, heart rate, blood lactate concentration, rate of perceived exertion, age, sex, body size and physical fitness. 2. The same variables were measured in 55 adolescents of both sexes with insulin-dependent diabetes mellitus of about 12 years duration and were analysed with respect to the healthy control group, to degree of metabolic control and to late diabetic complications. 3. In healthy adolescents the pressure response was not related to sex or age. When compared with control subjects diabetic patients had a higher diastolic blood pressure at rest and a more marked blood pressure increase, 23 versus 19 mmHg W-1 kg-1 body weight, during exercise with no sex difference. The blood pressure rise was not related to metabolic control, glomerular hyperfiltration or physical fitness. 4. Prolonged exercise tests were no more informative regarding the blood pressure response to exercise than the stepwise increased load test. Analysing the blood pressure increase versus relative work load (W/kg body weight) during exercise reveals blood pressure differences otherwise not noted. A diabetic patient with blood pressure above the 97.5% confidence limit during exercise seems to have a higher risk of developing incipient nephropathy 5 years later.

Adolescent↗

Lack of the latent transforming growth factor beta binding protein in malignant, but not benign prostatic tissue.

Transforming growth factor beta (TGF-beta) is a family of proteins which act as a potent growth inhibitor for most cell types including epithelial cells. TGF-beta is synthesized as latent high molecular weight complexes, composed of TGF-beta, the NH2-terminal part of the TGF-beta precursor and the third molecule, the latent TGF-beta binding protein (LTBP). We here ascertain that TGF-beta is expressed in human prostatic cancer tissue as well as in cystectomized prostatic tissue and in materials from transurethral resections with benign prostatic hyperplasia, analyzed by immunohistochemistry. TGF-beta is observed in both epithelial cells and stromal cells. No significant correlation was obtained between TGF-beta expression in tumor cells and their degree of differentiation. However, analysis by immunohistochemistry using antibodies against LTBP revealed that specimens from histopathologically verified human prostatic cancer are mostly negative for this molecule, although it is expressed in cystectomized prostatic and benign prostatic hyperplasia tissues. These results indicate that in cystectomized prostatic and benign prostatic hyperplasia tissues, TGF-beta may be produced in a complex associated with LTBP; whereas in prostatic carcinoma, TGF-beta is produced without associating with LTBP. The biological significance of the production of TGF-beta in relation to LTBP and the possible association with prognosis are discussed.

Amino Acid Sequence↗

The subacromial bursa and the impingement syndrome. A clinical and histological study of 30 cases.

Biopsies from the subacromial bursa were obtained from 30 patients with an impingement syndrome and from an autopsy series of 13 "normal" shoulders. Bursal fibrosis seemed to be a characteristic of the patient group; inflammatory cells, found in 7/30 specimens from the patients, were not found in the autopsy series. The microscopic findings could not be predicted from peroperative observations. There was an association between a poor outcome of surgery and absence of bursal fibrosis.

Acromioclavicular Joint↗

In situ expression of mRNA for proto-oncogenes in benign prostatic hyperplasia and in prostatic carcinoma.

Nine cases of prostatic carcinoma and 5 cases of benign prostatic hyperplasia (BPH) were examined for the in vivo expression of mRNA by an in situ hybridization technique for cellular proto-oncogenes, c-myc, c-fos, and c-sis. The latter of which encodes the B-chain of the platelet-derived growth factor (PDGF). High levels of c-myc and c-sis mRNAs were demonstrated in one highly differentiated prostatic carcinoma. Signals were localized in epithelial cells, both in packed cancer cells and in benign hyperplastic cells with glandular differentiation. A lower level of c-fos mRNA was also detected in the same areas. Four other carcinoma specimens showed c-sis mRNA, three of which also expressed c-fos mRNA. One other carcinoma expressed only c-myc mRNA. Three BPH specimens also contained c-sis and c-fos mRNA with one also exhibiting c-myc mRNA in the glandular epithelial cells. The results support the possibility that local production of growth factors, i.e. PDGF, may play a role in proliferation of prostatic epithelial cells.

Genes, myc↗

Expression of Ki-67--a proliferation-associated antigen--in prostatic cancer.

The expression of the proliferation-associated antigen Ki-67 was studied in human prostatic cancer. The antigen was analyzed with an immuno-histochemical technique in TUR specimens. A correlation was seen between Ki-67 positivity and differentiation grade. All TUR specimens (15/15) with poorly differentiated carcinomas expressed the antigen. Moderately differentiated carcinomas constituted an intermediate group and slightly less than half of the cancers (12/27) were positive for the antigen. Only one of the highly differentiated carcinomas (1/12) expressed the antigen. All TUR specimens from patients with benign prostatic hyperplasia (8/8) were negative. The effect on Ki-67 positivity was also investigated in a human prostatic cancer heterotransplanted to nude mice and subjected to ionizing irradiation with or without concomitant estramustine treatment. The antigen expression was compared with that seen in tumour tissues from untreated mice and from mice treated with estramustine alone. A pronounced effect was seen in the combination treatment group with an approximately 50% reduction of the Ki-67 positive cells. The results are discussed in relation to prognosis and follow-up after radiation therapy and the possible use of estramustine in combination with radiation therapy.

Animals↗

Modal DNA values and estramustine-binding protein (EMBP) as prognostic markers in prostatic cancer.

In this study, we have investigated the model DNA values and the expression of estramustine-binding protein (EMBP) in formalin-fixed and paraffin-embedded TUR specimens from 76 untreated patients with prostatic cancer. In addition, specimens from 13 patients were analyzed for tumour EMBP expression only. Ploidy was measured as diploid, tetraploid and non-tetraploid aneuploid or aneuploid in the near-diploid region. All patients had been referred during 1978-1981, and were subjected to TUR due to urinary obstruction. Survival data were obtained for all patients through March 1988. Statistical analyses were performed using a Cox's regression model with respect to survival and cause specific survival and correlated to the DNA pattern and the expression of EMBP. The existence of a near-diploid aneuploid cell population as well as poor differentiation grade were both statistically significantly correlated with poor survival. Near-diploid aneuploid cell lines were seen in 9/76 (12%) of the patients and were also seen in well differentiated cancers (4/17). The expression of EMBP was most abundant in the moderately differentiated cancers. However, all prostatic cancer specimens investigated were positive for the antigen. Patients with poorly differentiated carcinomas and high EMBP expression showed a tendency towards better prognosis than those with poorly differentiated carcinomas and low EMBP expression. The present patient material was, however, too small to show a statistically significant correlation between EMBP and survival.

Aged↗

Histopathological and immunohistochemical analysis of lung tumors: description of a convenient technique for use with fine needle biopsy.

In this paper we describe a convenient procedure for use with fine-needle biopsy in the diagnosis of lung and medistinal tumors. Cells obtained from a fine-needle aspiration are suspended in a formaldehyde solution and allowed to sediment onto a polycarbonate filter, using a filtering device specially designed for this purpose. The filter with the aspirated cells is then embedded in paraffin and thereafter sectioned and stained in a routine manner. The main advantages with this technique, instead of cytology, are: 1. the cells are kept mainly intact, mostly in undisrupted clusters, and this increases the possibility of obtaining a specific diagnosis, a prerequisite for the diversified clinical management of malignant tumors: 2. possibilities exist, when necessary, of further immunohistochemical characterization of tumor cells in order to obtain a specific diagnosis without thoractomy. This could be of major importance when the management of certain tumors and infiltrates (i.e. those preferably treated by radio- and chemotherapy) does not require surgical intervention.

Adult↗

Expression of estramustine-binding protein (EMBP) and the proliferation-associated antigen Ki-67 in prostatic carcinomas.

The expression of EMBP and the proliferation-associated antigen Ki-67 was studied in in vitro cultured prostatic carcinoma cells and in tumor tissues removed by transurethral electroresection (TUR). EMBP was found to be expressed predominantly in the moderately differentiated carcinomas. A technique based on the immunohistochemical analysis of fine needle specimens was also evaluated. This technique is of potential interest in prospective studies and in monitoring the effect of therapy. Ki-67 was found to be expressed in the prostatic carcinoma cell line (DU-145) studied, as well as in TUR specimens. This antigen reflects the proliferative characteristics of the tumor and may prove useful with respect to prognostic information and choice of appropriate therapy.

Antibodies, Monoclonal↗

Automatic analysis of Papanicolaou smears by digital image processing.

Papanicolaou smears from 378 patients were analyzed in a fully automated microscope system using an image analysis technique. The logic of the system subdivided the smears into "normal" (63%), "not possible to analyze in the machine" (17%) and "positive" (20%). The results have been compared with the conventional screening method available today taking into consideration the definition problems of a true diagnosis, cytopathological and histopathological consensus, reproducibility, sample-taking and interpretation mistakes, etc. As 37% (rejected and positive) of the smears in this particular study were analyzed visually after machine prescreening, it could be demonstrated that the false-negative rate among the remaining 63% of the specimens was significantly lower among the machine-screened smears when compared with visual screening if the results were correlated with histopathological consensus. The results clearly indicate that the technology required to build computerized microscope systems, which are able to automatically sort out at least two thirds of Papanicolaou smears is available today. The only limiting factor is the cost-benefit relationship.

False Negative Reactions↗

Frequent occurrence of short complementary sequences in nucleic acids.

The hypothesis, that nucleic acids which code specifically interacting receptor and ligand proteins contain complementary sequences was tested. Human insulin mRNA (HSINSU) contained 16 sequences which were 23.8 +/- 1.4 nucleotides long and were complementary to the insulin receptor mRNA (HSIRPR, 74.8 +/- 1.9% complementary matches, p less than 0.001 compared to randomly occurring matches). However, when examining 10 different nucleic acids (coding proteins not interacting with the insulin receptor), 81 additional sequences were found which were also complementary to HSIRPR. Although the finding of short complementary sequences was statistically highly significant, we concluded that this is not specific for nucleic acids coding specifically interacting proteins.

Base Sequence↗

Nonantral gastric carcinoid tumours associated with hypergastrinaemia.

Nonantral gastric carcinoid tumours in association with pronounced hypergastrinaemia are reported in 6 patients. It is suggested that the hypergastrinaemia, as a result of lack of a negative acid feedback inhibition in an achlorhydric stomach, promoted the tumour development, possibly initiated by action of carcinogenic nitrosamines, in the gastric juice.

Adult↗

[Histologic scoring system for various cancers of the external ear].

A histological scoring system was created to determine the aggressiveness of basal cell carcinomas of the head and neck and to determine which squamous cell carcinomas of the external ear will develop metastases. Basal cell carcinomas of the external ear were the most aggressive. The parameters depth of growth and mode of invasion were the most valuable in predicting metastases.

Basal Cell Carcinoma↗

Retroperitoneal sarcoma treated by surgery.

A retrospective analysis of extensive surgery with resection of retroperitoneal sarcoma and total or partial resection of adjacent organs in 15 patients is presented. Dominating symptoms were a palpable mass (80%). The tumor was felt in all patients. In 9 of 10 patients, ultrasonography showed a solid tumor with retroperitoneal location. In 14 patients (93%) the tumor was removed, in 11 of them adjacent organs also. Five of the patients were subjected to more than one operation because of tumor recurrence. Two patients died postoperatively. Six patients are alive without tumor recurrence; and three, with recurrence 18 to 62 months after the first operation. Four patients died 5--24 months after primary operation. In seven patients (50%), the tumor recurred locally. Surgery for recurrent tumor was beneficial. Complete surgical removal provides the most effective therapeutic approach. Routine second-look operation within a year after primary surgery may be a way to improve the results. Adjuvant cytostatic therapy could be considered.

Adult↗

Basal cell carcinoma in the head and neck. The importance of location and histological picture, studied with a new scoring system, in predicting recurrences.

A scoring system for judging the aggressiveness of basal cell carcinomas of the head and neck is devised, based upon 258 tumours from 123 patients. This system is discussed, and we suggest using the depth of growth, the degree of palisading and the narrow epithelial strand formation (narrow strands) as a scoring basis. It is shown that tumours located on the ear are more aggressive than tumours in other places. Tumours on the nose often recur, even though their histological picture is not that aggressive. This phenomenon is also discussed. For proper scoring, an excisional biopsy should be performed unless the tumour is very small. Recurrent tumours and tumours treated with X-ray also have a higher score.

Basal Cell Carcinoma↗