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Biomedical subjects

J Spona

Publications and source records attributed to J Spona.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies].

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Adenocarcinoma↗
PubMed1990

Impaired production of tumor necrosis factor in breast cancer.

Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired.

Antineoplastic Agents↗
PubMed1990

Medroxyprogesterone acetate lowers plasma corticotropin and cortisol but does not suppress anterior pituitary responsiveness to human corticotropin releasing factor.

The endocrine action of medroxyprogesterone acetate (MPA) has been claimed to be of a glucocorticoid-like nature. Upon clinical observation, MPA has been shown to improve life quality and overall well-being in patients with advanced breast cancer, renal carcinoma, prostatic carcinoma, and uterine adenocarcinoma. The authors have evaluated MPA endocrine action by the administration of human corticotropin releasing factor (hCRF) in a 90-minute assay in 15 patients with advanced breast cancer or renal cell carcinoma both, before the initiation of oral high-dose MPA treatment (1000 mg MPA) as well as after at least 10 days of therapy. The curves for corticotropin, beta-endorphin, and cortisol responses to hCRF of tumor patients who were tested before the initiation of MPA treatment were parallel to the curves of a healthy control group of probands tested under equal conditions, although at significantly higher respective hormone levels. In patients with malignant disorders assayed after MPA administration, both basal and peak hormone levels were found to be comparable with values obtained in healthy controls. In conclusion, MPA appeared to act at a suprapituitary level since pituitary responsiveness to hCRF was preserved under MPA treatment. Moreover, it appeared that MPA brought the hormonal stress state found in patients with malignant tumors back to normal.

Administration, Oral↗
PubMed1990

Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer.

An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.

Adult↗
PubMed1990

[Treatment concepts in tubal pregnancy].

The incidence of tubal pregnancy has increased markedly over the past years. Reasons for this are increased infections of and operations on the tubes and also improved diagnosis of the condition. The development of sensitive pregnancy tests, a constant improvement in ultrasound, introduction of laparoscopy and last, but not least, an increase in the degree of awareness amongst the general public have led to a much earlier diagnosis of tubal pregnancies. Therefore, it is possible to treat tubal pregnancies in a more conservative fashion operatively but also medically.

Dinoprost↗
PubMed1990

[Breast cancer in the male. A long-term follow-up study of 55 patients].

Between 1964 and 1988, 55 male patients were treated for breast cancer. Fifty-one patients were treated by radical mastectomy; only four patients underwent a simple mastectomy. Nineteen cases received postoperative radiotherapy, eleven cases chemotherapy, six cases adjuvant hormonal therapy, and one patient was submitted to orchiectomy. The five-year survival rate for tumors with nodal metastases was 37%, as compared with 57% for patients with negative nodes.

Adult↗
PubMed1990

Androgen receptors, serum androgen levels and survival of breast cancer patients.

Steroid receptor levels and serum androgen levels were determined in 61 breast cancer patients and 34 patients with non-malignant breast lesions. Testosterone and dehydroepiandrosterone-sulfate did not and androstenedione did show a difference between the two groups. Androgen levels had no influence on survival rates. Androgen receptor (AR) levels correlated with progesterone receptor levels, but not with estrogen receptor levels or with tumor stage. Patients with positive AR findings had a better survival rate; this was independent of tumor stage. AR findings may therefore be a prognostic index in breast cancer patients.

Adult↗
PubMed1990

A CA125 score as a prognostic index in patients with ovarian cancer.

Due to its high specificity (90%) and sensitivity (86%) measurement of CA125 has become well-established in patients with epithelial ovarian cancer. We have formulated a CA125 prognostic score and examined its validity as an additional prognosis index. This score is composed of two CA125 values (one determined preoperatively and one 1 month after operation). CA125 serum levels of 0-64 IU/ml received 1 point, levels of 65-299 IU/ml were given 2 points, and those greater than 300 IU/ml were given 3 points. These points are added to produce the CA125 prognostic score. Statistical comparison demonstrated that patients with scores of 2 or 3 had a significantly (P = 0.0005) better prognosis than patients with scores of 4, 5 or 6. The classical prognostics features such as the FIGO stage, residual tumor mass and ascites were found to correlate with the CA125 prognostic score.

Adult↗
PubMed1990

[Hypergonadotropic amenorrhea (WHO III) as osteoporosis risk].

In 21 patients, suffering from amenorrhoeic hypergonadotropic ovarian insufficiency (age 27 +/- 3 years [FSH: 43 +/- 10, LH: 40 +/- 8]), the bone density was measured by single-photon densitometry (SPA), before starting a hormonal replacement therapy with oestrogen/progesterone. Every 5 months, the trend in bone density change was measured in all cases. The bone density before hormonal treatment was lower in the WHO III-group (1.36 +/- 0.21 g/cm; 1.09 +/- 0.26 g/cm2) than in the age-matched group (1.57 +/- 0.21 g/cm; 1.28 +/- 0.31 g/cm2). Bone density increased after hormonal therapy (p less than 0.05). These results point to the necessity of hormonal replacement therapy in cases of WHO III.

Adolescent↗
PubMed1990

Oestrogen and progesterone receptor content as a prognostic factor in advanced epithelial ovarian carcinoma.

Levels of oestrogen receptor (ER) and progesterone receptor (PgR) in ovarian cancer tissue were examined with regard to their prognostic importance for survival in 179 patients with primary epithelial ovarian cancer stage III or IV in relation to: FIGO-stage, histological type, histological grade, age, ascites, and postoperative residual tumour. Hormone receptor content was determined with the DCC-method, receptor values higher than 9 fmol/mg protein were considered positive. Response to postoperative chemotherapy was significantly correlated with PgR content (80% responders in the group with PgR positive tumours and only 61% responders in the group with PgR negative tumours). A Cox proportional hazards regression model identified histological grade, residual tumour, age and PgR content as independent prognostic factors for survival in advanced epithelial ovarian carcinoma. PgR content had particularly significant prognostic relevance for patients with postoperative residual tumour mass less than or equal to 2 cm in diameter. Within this group of patients, those who are PgR positive have a 2-years survival probability of 83% compared with only 51% in the PgR-negative group.

Female↗
PubMed1990

Hormone receptors in pubic skin of premenopausal and postmenopausal females.

Various functions of the skin are hormone-dependent. Recently hormonal involvement in aging processes of the skin has attracted increasing interest. The rapid onset of aging of the skin from the climacterium on seems to be correlated with the decrease of estrogens. In order to evaluate hormonal stimulability of the skin a study of hormone receptors was performed in pre- and postclimacteric women. Pubic skin of a total of 106 females was obtained during gynecologic operations for determination of estrogen receptors (ER), androgen receptors (AR) and gestagen receptors (PgR) by saturation analysis. In the preclimacteric group consisting of 62 females with a mean age of 39.6 +/- (SD) 6.5 years the operations were performed in the luteal phase of the menstrual cycle. The results were compared with those of 44 postmenopausal females with a mean age of 63.2 +/- 9.4 years. AR concentrations were significantly lower in the skin of postmenopausal women. 47.4% positive findings with a mean receptor level of 15.3 +/- 33.3 fmol/mg protein were to be found against 85.2% positive AR with a mean level of 31.4 +/- 20.3 fmol/mg protein in the ovulatory cycling females. These findings were of high significance. In addition, diminished PgR in the postmenopausal group were noted for incidence and mean receptor levels. PgR were positive in 18.4% with a mean level of 34.2 +/- 72.8 fmol/mg protein versus 36.3% with a mean receptor level of 34.2 +/- 72.8 in the ovulatory group. In contrast, no significant differences between ER of premenopausal and postmenopausal skin became evident. Results of hormone receptor determinations in the premenopausal and postmenopausal group with regard to the aging process are interpreted.

Adult↗
PubMed1990

Hyperandrogenemia as a cause of primary infertility.

A total of 205 female infertility patients were investigated for hormonal causes of infertility after other factors such as tubal dysfunction or andrologic disorders had been ruled out. Increased androgen serum levels were found in 72/205 (35.1%) of females. In 28/205 (13.7%), elevated prolactin serum levels were noted. 119/205 (58%) of patients suffered from primary infertility versus 86/205 (42%) with secondary infertility. The incidence of hyperandrogenemia was higher in the primary infertility group (p less than 0.0015). No differences relative to hyperprolactinemia were noted between the two groups. Computerized tomography and sonographic methods did not reveal tumors in any of the subjects where serum concentrations of testosterone and dehydroepiandrosterone sulfate were greater than 2 ng/ml and 7 micrograms/ml, respectively. Present data combine to suggest that the determination of androgen serum levels is of major importance when investigating infertile patients.

Adolescent↗
PubMed1990

Determination of HER-2/neu amplification and expression in tumor tissue and cultured cells using a simple, phenol free method for nucleic acid isolation.

A rapid, simple and non-toxic procedure for the simultaneous isolation of DNA and RNA from tumor tissue and cells grown in vitro is described. Guanidinium isothiocyanate was used for homogenization of tumor tissue and for cell lysis. Separation of proteins, DNA and RNA was carried out by isopycnic centrifugation in cesium trifluoroacetate. DNA was further purified by salting out residual protein. Nucleic acids prepared by this method from 47 primary human carcinomas and 17 human cell lines were analysed for amplification and expression of the HER-2/neu proto-oncogene. 2- to 10-fold amplification of HER-2/neu was noted in 7/22 mammary carcinomas (32%) and in 4/14 ovarian carcinomas (28%). No amplification of the proto-oncogene was found in 4 laryngeal carcinomas, 1 pharyngeal carcinoma, 2 retrolingual carcinomas, 3 gastric carcinomas and 1 kidney carcinoma. HER-2/neu overexpression was observed in 6/22 of mammary carcinomas (27%) and 7/14 of ovarian carcinomas (50%). No overexpression was found in all other carcinomas studied. Concordance between amplification and overexpression was noted in 3 mammary and 4 ovarian carcinomas, respectively. 3 mammary and 3 ovarian carcinomas showed overexpression without amplification. 5 human mammary carcinoma cell lines showed both amplification and overexpression of HER-2/neu. In two mammary carcinoma cell lines (MDA MB-453 and ZR 75-1) overexpression was noted without amplification of the proto-oncogene. These data combine to suggest that mechanisms other than gene amplification may also lead to overexpression of the HER-2/neu protooncogene in cancer cells.

Blotting, Southern↗
PubMed1990

Endocrine parameters in acne vulgaris.

Hormonal parameters (see below) were determined in 78 male acne patients of both sexes (mean age 21.2 +/- 3.8 years; (mean +/- S.D.) and compared with 63 controls (25.0 +/- 4.2 years). In a female group consisting of 60 patients acne (23.2 +/- 5.0 years) and 28 controls (26.1 +/- 5.7 years) of age, blood sampling was performed in the luteal phase of the menstrual cycle. Testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (A), free testosterone (FT) and 17-hydroxy-progesterone (17-OHP) were determined by standard radioimmunoassay methods. In addition, sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), 17 beta-estradiol (E2) and cortisol (F) were evaluated. Moreover, the counts of acne lesions in the face were performed in 34 males and females patients in order to investigate possible correlations between hormones and acne lesions. The results in the male group revealed a significant elevation only for F but not for the other hormones. However, the female acne group significantly elevated levels of T, DHEA and F and a decrease of E became apparent. In addition, the correlation between both free and total T and acne lesions were found in the total of males and females. In the female group, free T and total A were found to correlate with acne lesions. The evaluation of these results indicates that androgens play a more important role in female than in male acne at the hormonal and at the peripheral level in skin. Another interesting finding was the significant increase of F in both male and female acne subjects, thus stressing the role of suprarenal involvement.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Association of increased lytic effector cell function with high estrogen receptor levels in tumor-bearing patients with breast cancer.

Tumor-bearing patients with breast cancer were assayed for their natural killer (NK) cell activity and for the function of activated cytotoxic T-cells, as assessed by lectin-dependent cellular cytotoxicity (LDCC). Tumor-bearing patients with breast cancer had a significant increase in NK activity and in LDCC, as compared with healthy control individuals. Although the enhanced NK cell activity and LDCC were closely associated with high levels (greater than 31 fmol/mg) of estrogen receptor (ER) content in the primary tumor, no other clinical or histologic correlation between the increase in either parameter of cytotoxic effector cell function could be found. Thus, ER levels greater than 31 fmol/mg might be associated with increased cytotoxic effector cell function in tumor-bearing patients with breast cancer.

Breast Neoplasms↗