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Biomedical subjects

J Spona

Publications and source records attributed to J Spona.

At least 127 records · Page 7Linked to original sources

Androgen receptor in hirsutism and acne.

Hyperandrogenism may result in acne and hirsutism. On the other hand, acne and hirsutism may occur without elevated androgen serum levels. An important point of androgen action is the target organ sensitivity at the receptor level. In the present study, androgen receptor (AR) determinations by saturation analysis were performed in 36 hirsute as well as in 11 female and 52 male acne patients. A small group of endocrine healthy patients served as control group. For AR analysis, the predilection sites of the disease were chosen. In acne, also nonlesional skin served as control. 26% of the hirsute patients were AR-positive, with mean AR levels of 68 fmol/mg protein. Male acne patients were 50% AR-positive in acne lesions and 60% positive in their nonlesional skin. The mean AR levels were 25 and 38 fmol/mg protein, respectively. The control group was 27% AR-positive, with mean AR levels of 15 fmol/mg protein. Female acne patients were 3/11 positive in lesional and 1/11 positive in nonlesional skin. The mean AR levels were 25 and 35 fmol/mg protein, respectively. The female control group was in 3/13 cases AR-positive, with a mean level of 8 fmol/mg protein. Comparison of the AR levels indicates hirsutism as the mostly androgen-dependent dermatosis. No correlation between AR and androgen serum levels was demonstrated. This finding suggests that androgen action at the target organ level in both dermatoses may be independent of peripheral serum levels of hormones.

Acne Vulgaris↗

Enzyme immunoassay and Scatchard plot estimation of estrogen receptor in gynecological tumors.

Tissue samples of three endometrial carcinomas, seven ovarian carcinomas, and 24 mammary carcinomas were analyzed for estrogen receptor (ER) by enzyme immunoassay (EIA) and a conventional dextran-coated charcoal (DCC) method. In addition, ER and progesterone receptor were assayed by DCC only in 68 ovarian carcinoma specimens. All three endometrial cancer specimens showed elevated ER values by both assays. As with mammary cancers the ER-EIA values tend to be higher than DCC values. It was intriguing to note that negative Scatchard plot data resulted in residual ER levels in the EIA system. Also four ovarian cancer specimens with negative ER values by the DCC assay had detectable levels by ER-EIA, and three of these four had ER-EIA values less than or equal to 10 fmol/mg of protein. Of the ten breast cancers with negative DCC values, seven were less than or equal to 10 fmol/mg of protein by the ER-EIA. Good correlation (r = 0.88) between EIA and Scatchard plot data was calculated from ER data of 24 mammary carcinoma tissue samples. Receptor assays in 68 ovarian cancer patients indicate that ER determinations should become a useful tool in the management of patients bearing this carcinoma. In addition, receptor determinations may improve the possibility of predicting which well differentiated Stage I ovarian carcinomas are likely to recur. Present data combine to suggest that ER-EIA may become a useful diagnostic laboratory tool.

Breast Neoplasms↗

Monitoring the cytotoxic potential of a sequential polychemotherapy (adriamycin/cisplatin-vincristine/cyclophosphamide-high dose methotrexate) in patients with advanced ovarian cancer with the tumor marker CA-125.

The cytotoxic efficacy of a new sequential chemotherapy, called changing-scheme (adriamycin/cisplatin-vincristine/cyclophosphamide-HD-methotrexate), was investigated parallel to the course of CA-125 serum levels. Sixty-three percent of the women studied achieved remission under this chemotherapy. A correlation between clinically proven tumor stage and CA-125 serum level was found in 90%. The cytotoxic potential of the three single parts of the changing-scheme was demonstrated based on decreasing CA-125 serum levels. The value of the tumor marker CA-125 for the follow-up of patients with malignant ovarian tumors is discussed in detail.

Antigens, Neoplasm↗

Estrogen receptor analysis on biopsies and fine-needle aspirates from human breast carcinoma. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.

Monoclonal antibodies against estrogen receptor (ER) were used for determination of ER status immunocytochemically in histologic specimens from 192 primary breast carcinomas. All tumors were also assayed biochemically for ER with the dextran-coated charcoal method (DCC). The comparison of biochemically and immunocytochemically determined ER status showed concordant results in 80% (P less than 0.0001). In only 2 cases (1%) with low ER levels (less than 20 fmol/mg protein) immunocytochemistry failed to detect ER. ER positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined ER levels (P = 0.0001). In a series of fine-needle aspirates of 34 breast carcinomas sufficient cell material was available for ER immunocytochemistry (ER-ICA). Overall, the results of ER-ICA in fine-needle aspirates were concordant with ER-ICA in histologic specimens in 88% of the samples. In a few cases with weak positivity of ER-ICA in histologic specimens, ER-ICA was negative in fine-needle aspirates. In no case was there a false-positive immunocytochemical ER determination in a tumor aspirate. Thus, ER-ICA seems to be a reliable assay which can be performed in histologic and cytologic specimens.

Antibodies, Monoclonal↗

[Significance of hormone receptors of breast cancer cells for the duration of a disease-free interval].

The importance of the presence of hormone receptors of cells derived from breast cancer tissue for the duration of the relapse-free interval was evaluated in 41 patients with stage II breast cancer. After modified radical mastectomy with axillary lymphadenectomy the patients received radiotherapy and adjuvant polychemotherapy and/or hormone therapy. There was no indication of metastases in any patient at the time of operation. There was a significant correlation of the relapse-free interval to tumor size (p less than 0.05), to the number of involved lymph nodes (p less than 0.0005), and also to the presence of the progesterone receptor (PgR), which seemed to play a more important role in this context than the oestrogen receptor (ER) (p less than 0.001). We conclude from this study that the evaluation of the PgR in breast cancer cells is important for the prognosis of the duration of the relapse-free interval.

Antineoplastic Combined Chemotherapy Protocols↗

The human tumour cloning assay in the management of breast cancer patients.

A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01).

Breast Neoplasms↗

[Clinical significance of the tumor marker CA-125 for the preoperative diagnosis and postoperative management of patients with malignant ovarian cancers].

The ovarian carcinoma-associated antigen CA-125 was determined in 144 women with various gynecological tumors (ovarian, breast, uterine), by using the heterologous monoclonal antibody OC-125. In 90% of the malignant ovarian tumors positive CA-125 values were correct, whereas their negative values were correct in 88% of the benign ovarian lesions. In 90% of the 58 patients with malignant tumors, where it was possible to observe tumor marker concentrations as well as the simultaneous tumor behaviour, a good correlation was found. Therefore, CA-125 serum determinations seem to be useful in the preoperative assessment of the importance of palpable ovarian tumors, as a parameter for evaluating therapeutic measures, and for early detection of recurrences of ovarian tumors.

Adult↗

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.

Biopsy↗

Medroxyprogesterone acetate therapy in hirsutism.

In a pilot study, 26 hirsute females were treated with medroxyprogesterone acetate (MPA). We used an ointment containing 0.2% MPA in 13 patients, subcutaneous injection of MPA into the hairy areas of the face in five patients and intramuscular injection of low doses of MPA in 13 patients, each for an average duration of 16 weeks. The best clinical result was achieved by subcutaneous injection, the next most successful was the intramuscular injection, and the least successful was the topical application. Hair diameter measurements, carried out in 12 patients, were found to be reduced by 33% on average. Serum androgen levels, measured monthly, remained unaffected by topical treatment, but were decreased by intralesional and intramuscular injection. The clinical improvement with topical therapy despite the lack of effect on serum androgen levels supports the idea that MPA works partly at the cellular level. The intralesional and systemic injection of MPA may exert an effect both by systemic androgen suppression and a local action.

Administration, Topical↗

Sebum suppression by benzoylperoxide.

Sebum excretion rate (SER) was determined by thin-layer chromatography and based on densitometric data in 9 male and 5 female patients suffering from acne during treatment with 10% benzoylperoxide (BPO). BPO was applied to the forehead (treatment area), whereas gel only was applied to the chest (control area) for 6 weeks. SER decreased in 10/14 subjects, no change was found in 1 subject and 3 patients exhibited an increase in SER. Suppression varied between 12 and 86%. Concomitant SER reduction in control and treatment areas was noted in 6 patients. When treatment and control areas of individual patients were considered for data evaluation, SER decrease was noted in only 4 out of 14 subjects. Similar results were obtained when free fatty acids, triglycerides and squalene data were analyzed. Combined, these data suggest that BPO may affect SER in some patients. The present experiments indicate the importance of adequate controls in such studies.

Acne Vulgaris↗

Early detection of pregnancy by new beta-hCG monoclonal urine test.

1,066 urine samples were assayed by beta-human chorionic gonadotrophin (beta-hCG) monoclonal pregnancy test with a sensitivity of 150 IU hCG/l. Tests were performed in 5 independent laboratories and results were compared with those of pregnancy tests which were used routinely. Urine samples which showed discordant results under evaluation were reassayed for beta-hCG using radioimmunoassay. 569 urine samples were from nonpregnant women, and a consistent result with comparison pregnancy tests was achieved in 97.19% of urine samples. The trial test from 389 urine samples of pregnant women was 99.49% in accordance with routine pregnancy tests. Results from 108 urine samples of women over 40 years of age indicate the high specificity of the new beta-hCG monoclonal pregnancy test. Titration experiments showed 63% positive tests at 150 IU beta-hCG/l. Data presented combine to suggest that this new monoclonal pregnancy test is a valuable aid in diagnosing early pregnancy. It may also be used in the diagnosis of tubal pregnancy and in other ectopic processes.

Adult↗

Steroid hormone levels in serum and skin receptor concentrations in hirsutism.

In 36 women androgen (AR), estrogen (ER) and progesterone (PgR) receptor were determined by dextran coated charcoal assay and subsequent Scatchard plot analysis in skin slices obtained from hirsute areas under local anesthesia. The biopsies were performed between day 18-21 of the menstrual cycle. Concomitantly venous blood was sampled in these and additional 14 patients for radioimmunoassay estimation of serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), estradiol (E2) and prolactin (PRL). However, it should be noted that all receptors and hormones were not examined in all patients. The incidence of ER-positive patients was smaller (i.e. 17%) than previous findings in acne and normal skin, while 26% of the examined patients were AR-positive. This result was similar to findings in acne, whereas the receptor levels are three times higher than in acne lesions. This suggests a greater androgen sensitivity of hirsute areas compared to acne lesions. Two out of 10 examined patients were PgR-positive. T was elevated in 63%, DHEA-S in 50% and A in 37% of examined patients. Lack of correlation between hormone serum levels and corresponding receptors concentration indicates a direct involvement of hormone action at the cellular level. The data combine to suggest that greater target organ sensitivity was responsible for hirsutism in those patients with normal androgen serum levels, while the absence of receptors in skin samples may characterize patients with idiopathic hirsutism.

Adult↗

Enzyme activities in human breast tumor cells and sera.

Galactosyltransferase (GalTF), sialyltransferase (SiaTF), fucosyltransferase (FucTF), 5'-nucleotidase (5'Nucl), and ADP-ribosyltransferase (RibTF) were determined in three subcellular fractions of tumor cells and adjacent control tissue from 20 patients with small primary infiltrating ductal adenocarcinomas of the breast. Viable, as pure tumor cell populations as possible were isolated, subfractionated, and their enzyme levels compared to those in the patients' sera. The activities in tumor cells of the three glycosyltransferases were two- to seven-fold higher, whereas 5'-Nucl and RibTF showed reduced activities when compared to adjacent noninvolved tissue. Serum GalTF and SiaTF were slightly elevated in early mammary carcinoma, whereas FucTF, 5'Nucl, and RibTF were decreased in comparison with a control group. The proposed tumor origin of circulating enzymes could not be confirmed. Surprisingly, only for RibTF could a correlation between tumor and serum activity be established; a weak correlation was found for SiaTF. However, no such relationship could be determined for GalTF, FucTF, or 5'Nucl. In conclusion, the enzyme profile of the tumor cell does not, except for RibTF, appear in the serum. Serum enzyme profiles, therefore, do not permit detection of the early stages of breast cancer. A high correlation between RibTF activity and cytosol estrogen and progesterone receptor levels has been determined in tumor cells, possibly indicating slower growing, more differentiated types of breast tumors.

5'-Nucleotidase↗