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R Jakesz

Publications and source records attributed to R Jakesz.

At least 127 records · Page 7Linked to original sources
PubMed1986

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↗
PubMed1985

[Adjuvant chemotherapy in breast cancer. Report and commentary on the NIH Consensus Development Conference, Bethesda, Maryland, U.S. 9-11 September, 1985].

Adjuvant chemo- and endocrine treatment in breast cancer are effective treatment modalities. However, the cure rate in this disease is still not satisfying. Using prospective clinical trials further treatment procedures should be evaluated. Based on data presented at the 1985 Consensus Development Conference, treatment recommendations can be made for patients, who are not willing to participate in clinical trials: Regardless of steroid hormone receptor status combination chemotherapy has proven significant effectiveness in premenopausal patients with axillary node metastases, however in patients without nodal involvement this treatment is generally not recommended. For patients with receptor-negative and/or undifferentiated carcinomas chemotherapy should be considered. Postmenopausal patients with axillary node metastases and receptor-positive tumours should be treated with tamoxifen. In those with positive nodes and negative receptors chemotherapy may be considered. There is no indication for routine adjuvant chemotherapy in postmenopausal patients with negative nodes regardless of hormone receptor levels.

Axilla↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Carcinoembryonic antigen (CEA) plasma level determination in the management of gastric cancer patients.

Carcinoembryonic antigen (CEA) levels of 161 patients with gastric cancer and of 12 patients with noncarcinomatous diseases of the stomach were retrospectively analyzed. In this study, we examined the correlation between CEA level and histologic type, T and N stage, and the value of the preoperative CEA determination for diagnosis, operability and prognosis for patients with gastric cancer. Summarizing our results: There exist significant higher CEA levels in patients with gastric cancer in comparison with patients with noncarcinomatous disease of the stomach (p less than 0.01), but the absolute CEA titer is not a reliable parameter for the prediction of the existence or absence of gastric cancer for the individual patient. A positive correlation between the CEA level and the histologic type in the subgroup of radically operable patients was found, the intestinal type having lower titers (p less than 0.05). The operability of two different histologic entities (diffuse or intestinal type) was equally high. No conclusion can be drawn from CEA plasma levels concerning the operability of the individual gastric cancer patient; on one hand, 30% of the patients with normal preoperative CEA titers could not be radically operated, whereas 34% of the patients with elevated preoperative CEA titers (greater than 5.0 ng/ml) had radical surgery. Furthermore, the absolute value of the preoperative CEA level does not predict the course of the disease, whereas continuously rising postoperative CEA levels are indicative of tumor progression.

Aged↗
PubMed1984

[Surgical therapy of breast cancer: to operate radically or to preserve the breast?].

Surgical treatment, i.e. partial resection (R) versus modified radical mastectomy (M) in lymph node negative T1/2 patients and M versus the classical Halsted procedure (RM) in lymph node positive cases, as well as adjuvant treatment forms, namely chemotherapy (B) and chemoimmunotherapy (C) versus a control group treated by surgery only (A) have been evaluated in 241 patients with breast cancer follow up over a median observation time of 48 months. Whereas M showed significantly better results than R, no difference was detected between M and RM. The incidence of recurrence in the R group did not appear to be markedly reduced by cytotoxic treatment. In the same way, the data from a retrospective study on non-randomized patients treated by breast resection, showed a relatively high local recurrence rate (23.6%) at a median observation level of 10 years. Considering the various forms of surgical treatment for operable breast cancer by analysing the data from retrospective studies and prospective randomized trials from the literature as well as our own results, the only recommendation for the standard treatment of patients with primary operable breast cancer should be nothing less than modified radical mastectomy. Breast-conserving treatment forms should be tested only within the framework of controlled clinical trials.

Breast Neoplasms↗
PubMed1984

[Adjuvant endocrine forms of therapy in breast cancer].

Determination of oestrogen receptor (ER) and progesterone receptor (PgR) allows a prediction of response to endocrine treatment in patients with metastasizing breast cancer. Randomized trials of ovariectomy or irradiation of the ovaries showed a prolonged recurrence-free interval in these patients as compared with a non-castrated control group, but no influence on the overall survival rate. All these studies were performed without prior knowledge of the ER and PgR status of the primary tumour. Randomized trials with the anti-oestrogen, tamoxifen showed a prolonged recurrence-free interval; one study showed significantly prolonged overall survival. Studies employing combined chemo-hormonal therapy showed a lower recurrence rate in postmenopausal patients with ER + PgR + tumours, as compared with patients treated by chemotherapy alone. Adjuvant treatment prolongs the recurrence-free interval in postmenopausal patients. The follow-up periods are too short as yet to allow final conclusions regarding influence on the overall survival rate to be drawn. An optimal adjuvant endocrine treatment schedule in premenopausal patients with ER + PgR + tumours needs to be established in future studies.

Breast Neoplasms↗
PubMed1984

Influence of cell proliferation and cell cycle phase on expression of estrogen receptor in MCF-7 breast cancer cells.

In the present study, the effects of cell cycle phase and proliferation rate on the expression of specific estrogen binding activity were explored in hormone-dependent human breast cancer cells. A technique was developed to alter the proliferative rate of MCF-7 cells by plating at different densities. The doubling time ranged from 20 to 48 hr, showing a negative relation to the number of plated cells. Slowly proliferating cells had accumulated more than twice as much estrogen receptor (ER) activity as did fast-proliferating cells. Exposure of exponentially growing cells to isoleucine-deficient medium resulted in decreased thymidine incorporation and disappearance of detectable cellular ER activity. Overall protein synthesis was reduced by only 30% in cells growing in isoleucine-free medium. At 24 hr after release from isoleucine deprivation, ER levels are fully restored, although thymidine incorporation does not resume for an additional 6 to 8 hr, and increases in cell number are not seen for 24 hr. Exposure of exponentially growing cells to 2 mM thymidine for 24 hr produced partially synchronized MCF-7 cells (approximately 70%). Six hr after release from excess thymidine, cells reached S phase; after 9 hr, G2; and after 18 hr, G1. ER levels immediately and, 6 hr after release, remained unchanged, showed a slight increase at 9 hr, and showed an increase of about 50 to 60% at 18 hr. These data suggest that: (a) ER binding activity and DNA synthesis can be dissociated; (b) ongoing protein synthesis is necessary for maintenance of cellular ER activity; and (c) ER is apparently synthesized throughout the cell cycle, with some evidence that this is predominantly in G1 and G2.

Breast Neoplasms↗
PubMed1983

Continuous estrogen exposure in the rat does not induce loss of uterine estrogen receptor.

Cytosol estrogen receptor (ERc) and nuclear estrogen receptor (ERN) levels were investigated in rat uteri under different conditions of hormonal exposure. The amount of directly assayable receptor was closely related to the serum concentration of 17 beta-[2,4,6,7-3H] estradiol ( [3H]E2). A double injection technique was established to maintain serum levels of [3H]E2 which were sufficient to saturate receptor sites. Under these conditions, stable ERC and ERN levels are maintained throughout the study period. 30% of the total ER remains cytoplasmic in localization despite continuous hormonal exposure. Properties of ERC and ERN after 6 h of continuous hormonal exposure were investigated and found to be different from receptors found in these subcellular compartments 30 min after hormone injections. ERC from uteri 30 min after injection showed a faster sedimentation coefficient than ERC prepared 6 h after hormone treatment. ERC after 6 h of hormonal exposure showed a reduction of binding to calf thymus DNA adsorbed on cellulose in a cell-free system. ERC 30 min after [3H]E2 treatment had a biphasic dissociation pattern consistent with two different receptor populations, whereas uterine ERC obtained after 6 h of in vivo exposure to estradiol showed virtually no dissociation at 22 and 28 degrees C. In contrast to ERC, ERN 6 h after hormone injection sedimented faster than ERN obtained 30 min after treatment. KCl extractable ERN obtained either at 30 min or 6 h posthormone treatment showed biphasic dissociation kinetics at 22 and 28 degrees C, whereas KCl nonextractable ERN showed virtually no dissociation. Virtually all of the specifically bound ligand in cytosol and nuclear preparations was proven to be authentic E2. We conclude that total cellular receptor is quantitatively conserved during 6 h of continuous hormonal treatment. Nuclear receptor loss is not a requisite for receptor-mediated steroid function, although important time-dependent changes in receptor properties in both cytoplasmic and nuclear compartments do occur.

Animals↗
PubMed1983

Characteristics of different cytoplasmic and nuclear estrogen receptors appearing with continuous hormonal exposure.

Biochemical properties of cytosol estrogen receptor (ERC) and nuclear estrogen receptor (ERN) from rat uteri continuously exposed in vivo to 17 beta-[2,4,6,7-3H] estradiol ( [3H]E2) for 6 h have been studied on the basis of immunological recognition and chromatographic elution patterns. Overall concentrations of ERC and ERN did not change during this time period when receptor-saturating concentrations of [3H]E2 were maintained (Jakesz, R., Kasid, A., and Lippman, M. E. (1983) J. Biol. Chem. 258, 11798-11806); however, biochemical characteristics were different in ERC and ERN after short or long term hormonal exposure. When ERC from rats treated with estradiol for 30 min was applied to HAP or DEAE columns, two different ER binding components were seen. DNA binding in a cell-free system revealed that these binding components represented an activated and a nonactivated ERC population. After long term hormonal exposure (6 h), only one component of ERC with low DNA binding could be shown despite the preservation of an equivalent quantity of cytoplasmic binding activity. This binder does not react with a monoclonal antibody directed against extranuclear estrogen receptor species. These data suggest disappearance of the activated ERC population, with appearance of a new, immunologically nonrecognizable ERC species with 6 h of continuous hormonal exposure. Elution profiles of ERN on HAP chromatography reveal 2 different binding components at 30 min and at 6 h of continuous [3H]E2 exposure. There is an increase of the population eluted at higher molarity after 6 h of in vivo treatment. This later eluting binding component is the major DNA binder in vitro. ERN from both time points are recognized immunologically by monoclonal antibody. After reaction with the antibody, the sedimentation coefficient shifted to 8-9 S on sucrose gradients, but the previously described faster sedimentation of ERN extracted 6 h after injection persisted. We conclude that ER in both cellular compartments undergoes time-dependent alterations, which may be involved in the initiation of hormone action.

Animals↗
PubMed1983

Clinical and experimental aspects of hormone receptors in breast carcinoma patients.

Estrogen (ER) and progesterone (PgR) receptor contents were determined in 214 patients with primary mammary carcinoma. Premenopausal and postmenopausal females (43 and 48%, respectively) were found to be ER and PgR positive. ER levels between 100 and 500 fmol/mg protein were observed in 37% postmenopausal and 14% premenopausal patients, respectively. ER distribution between lymph node-positive and -negative patients did not differ significantly. Subjects without detectable ER had recurrences earlier than did subjects with ER. On the other hand, no differences in recurrence rates were noted when PgR-positive and -negative patients were compared. In addition, the determination of ER did not permit selection of patients for adjuvant cytotoxic chemotherapy. Furthermore, the action of tamoxifen was investigated in the rat pituitary as a model system. Tamoxifen was found to act as antiestrogen at the level of transcription by inhibiting the accumulation of estrogen-stimulated preprolactin mRNA. Combined data suggest that patients with positive lymph nodes and positive receptors may benefit from combined endocrine plus cytotoxic adjuvant chemotherapy.

Animals↗
PubMed1982

[The protective effect of systemic HCO3- administration on the gastric mucosa in shock].

Recent research has shown adequate mucosal blood flow and blood bicarbonate availability to be crucial in the prevention of gastric ulceration, yet the relative importance of these two factors is unknown. We studied the incidence of ulceration in rats subjected to hypovolaemic shock under varying conditions of blood flow and acid-base balance. At the start of the experiment 2 ml of 0.1 M HCl were instilled into the stomach. In the control series, severe systemic acidosis had developed after 2 hours of shock (mean arterial blood pressure 40 mm Hg) and 6 out of 6 stomachs were ulcerated. Mucosal blood flow, measured with radioactive microspheres, had drastically decreased. Prostacyclin, dissolved in 0.01 M phosphate, improved gastric blood flow, but did not help to correct acidosis, and 6 out of 8 stomachs were ulcerated. A higher degree of protection was observed when prostaglandin was dissolved in 0.16 M HCO-3. Intraarterial infusion of high concentrations of bicarbonate completely eliminated acidosis, with ulceration occurring in only 1 out of 6 rats infused with 0.5 M bicarbonate and in 1 out of 10 with 1 M bicarbonate. Blocking carbonic anhydrase with acetazolamide (100 mg/kg) completely prevented the protective effect of a 1 M HCO-3 infusion, and 6 out of 8 stomachs were ulcerated. Substituting TRIS buffer for bicarbonate in the infusion also eliminated acidosis, but neither concentrations of 1 M or 5 M buffer prevented the stomachs from ulceration (6 out of 6 with 1 M buffer and 5 out of 6 with 5 M buffer). We conclude that bicarbonate is the essential factor in prevention of ulceration in our shock model and that blood flow is also important as one component of a bicarbonate-dependent protection system involving carbonic anhydrase.

Acetazolamide↗
PubMed1981

[Steroid receptor levels in human breast carcinomas in relation to serum hormone levels in postmenopausal patients (author's transl)].

Serum levels of LH, FSH, HPRL, oestradiol, progesterone and testosterone were determined by radioimmunoassay in 45 postmenopausal patients in the morning before they were operated on for primary breast cancer. Cytosol oestradiol - (E2R) and progesterone receptor (PgR) levels were estimated by Scatchard plot analysis of saturation assays using the charcoal method. When serum hormone levels and receptor contents were correlated according to the distribution free test of Spearman, all correlations were found to be insignificant, with the exception of E2R/PgR (p less than 0.001).

Aged↗
PubMed1981

[Tumor histology and steroid receptors in breast carcinoma].

In Specimens of 115 patients with breast cancer 4 tumorparameters (tumorsize, tumorboder, nucleargrade, lymphocytic stromal reaction) 3 features of regional lymphnodes (sinushistiocytosis, T-cellreaction, lymphnode metastases) and estrogen and progesteron receptors were determined. A strong sinushistiocytosis and T-cellreaction could be verified mainly in metastases in free lymphnodes. The steroid receptor content does not correlate with histological parameters.

Breast Neoplasms↗