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M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 289 records · Page 16Linked to original sources
PubMed1989

[In vitro study of estradiol-linked nitrosourea in breast cancers in the mouse, rat and human: interspecies comparison].

In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-oestradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in mice and autochthonous methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats, as well as in 30 human primary breast carcinomas using the bilayer soft agar assay is described. Eighty-five percent of MXT tumours showed a more than 70% inhibition of colony formation in response to CNC-ala-17-E2. The MNU-induced model did not show this high degree of inhibition; only 5% of tumours showed an inhibition of up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. By contrast, in human breast carcinomas there was no statistically superior response to the hormone-linked preparation as opposed to the single agents. Thus, in MXT mammary carcinoma the in vitro results parallelled previous findings in vivo, whereas in the MNU-induced autochthonous tumour model this close in vivo-in vitro correlation was not observed. The discrepancy between in vivo and in vitro results found in the autochthonous rat model indicates that hormone-linked nitrosoureas should not necessarily be abandoned for the treatment of human breast carcinoma on the basis of negative in vitro results alone.

Animals↗
PubMed1989

Relations between chronic stimulation-induced changes in contractile properties and the Ca2+-sequestering system of rat and rabbit fast-twitch muscles.

This study compares changes in contractile properties, parvalbumin content, and Ca2+-uptake by the sarcoplasmic reticulum (SR) of low-frequency stimulated rat and rabbit tibialis anterior (TA) muscles. Time to peak tension increased 1.8-fold in 35-day stimulated rabbit TA, while no change occurred in rat TA. Isometric twitch tension increased 2-fold in rabbit TA, but was unaltered in rat TA. Parvalbumin (PA) content was more than 90% reduced in rabbit TA, but only 60% in rat TA after 35 days. At this time, PA content of the stimulated rat TA was still higher than that of normal rabbit TA. Taking into account the suggested role of PA as a cytosolic Ca2+ buffer, its decrease could lead to an impaired free Ca2+-decay with a prolonged active state and a higher tension output during a single twitch. This would explain why chronic stimulation led to an increase in isometric twitch tension in rabbit TA, but not in rat TA. The 1.6-fold rise in half-relaxation time of 35-day stimulated rat and rabbit TA most likely resulted from a 50% reduced Ca2+-uptake by the SR, due to a still unknown modification of the Ca2+-transport ATPase.

Animals↗
PubMed1989

Expression of epidermal growth factor receptor in benign and malignant primary tumours of the breast.

Using the monoclonal antibody EGF-R1, normal mammary gland and a series of 213 unselected primary breast tumours were investigated immunohistochemically for expression of epidermal growth factor receptor (EGFR). In normal breast EGFR was expressed in variable patterns in lobular, ductal, and myoepithelial cells. In fibroadenoma, EGFR was detectable in variable numbers of ductal and myoepithelial cells and in stromal fibroblasts. The myoepithelial compartment of 2 cystosarcomas phyllodes also expressed EGFR. Among the 197 carcinomas tested only 20.3% contained EGFR expressing tumour cells which represented a minority in 12.2%, the majority in 2.1%, and the entire neoplastic population in 6.1% of the cases. Again, non-neoplastic ductal remnants often contained EGFR positive myoepithelial and ductal cells whereas stromal fibroblasts expressed EGFR only occasionally. We conclude that in contrast to the normal state, EGFR-expression is a rather rare phenomenon in breast carcinoma cells, positively correlated with a declining grade of differentiation (p less than 0.025) and at least occasionally associated with squamous metaplasia within the tumour, that EGFR expression is not exclusively restricted to cells of the epithelial lineage, and that EGFR may have other functions not related to proliferation, since it is commonly detectable in myoepithelial cells.

Breast↗
PubMed1989

DNA index and cell cycle analysis of primary breast cancer and synchronous axillary lymph node metastases.

The DNA Index (DI) and the percentage of cells in S-phase (S-phase fraction, SPF) were measured by flow cytometry in 80 primary breast carcinomas and in 80 accompanying axillary lymph node metastases. The DI in primary tumors and metastases agreed in 61 cases (76%). Cases with diploid primary tumors revealed more constancy of the DI in comparison to the metastases than the cases with aneuploid primary tumors (91% and 70% respectively). The mean values of the SPF were in close agreement in the primary tumors and in the lymph node metastases (6.1% and 6.0% respectively). Differences between the SPF of the two groups could be detected only by the consideration of case-related data pairs. In 50 cases (62%), the percentage of SPF agreed approximately in primary tumors and in the correspondent metastases. The cases with diploid primary tumors revealed more agreement of the SPF in the primary site and the metastases than did cases with aneuploid primary tumors (78% and 56% respectively). In conclusion, diploid carcinomas and their metastases revealed more constancy of the DI and the percentage of SPF than aneuploid carcinomas. These findings agree well with a better prognosis of diploid mammary carcinomas, as reported in the literature. Comparisons between the DI and the SPF in primary tumors and the corresponding metastases could be a source of valuable information on the biological behaviour and the aggressiveness of mammary carcinomas.

Aneuploidy↗
PubMed1989

DNA flow cytometry, clinical and morphological parameters as prognostic factors for advanced malignant and borderline ovarian tumors.

Patients with malignant ovarian (n = 111) and borderline (n = 8) tumors (FIGO stage III/IV) underwent surgery and chemotherapy and were analyzed clinically (age, residual tumor after surgery) and morphologically (type, grade, psammoma body content), and by means of flow cytometry (DNA ploidy, S-phase fraction). Follow-up was 12-72 months for investigation of survival. Patients under 60 years of age (n = 18) with malignant tumors showed longer survival than patients over 60 (n = 93) (P = 0.078). Residual tumor was relevant for prognosis in malignant tumors only if macroscopically there was no residual disease (n = 13). There were no significant differences between residual tumors less than or equal to 2 cm (n = 61) and greater than 2 cm (n = 37). WHO typing was of little importance for survival analysis. Compared to borderline tumors (n = 8), serous (n = 65), endometrioid (n = 13), nonclassifiable (n = 12), mucinous carcinomas (n = 8), and nonepithelial tumors (n = 12) had a poor prognosis. Psammoma bodies were found in 25 patients with serous carcinomas, 7 of them had a high content. The prognosis for these 7 patients was much better than that for patients with a moderate or low psammoma body content (P = 0.006). Twenty-three epithelial tumors were graded G1, 28 were G2, and 47 were G3. However, grading was considered only as a prognostic factor in serous carcinomas (n = 65) (P = 0.028). A total of 199 DNA histograms from 119 patients were analyzed by flow cytometry (FCM). There were no correlations between tumor type and DNA ploidy or S-phase fraction. Seven of eight borderline tumor and all serous carcinomas with a high content of psammoma bodies were diploid combined with a low (less than or equal to 4%) S-phase fraction. DNA ploidy and S-phase fraction were excellent prognosticators. Of 99 epithelial malignant tumors, 35 were diploid and 64 were aneuploid. An S-phase fraction less than or equal to 4% was found in 39 patients, 4.1-10% in 73 patients, and greater than 10% in 23 patients. Diploid tumors and tumors with a low S-phase fraction showed the best survival (P = 0.007, resp. 0.0001). Our study emphasizes the importance of an accurate histology, including information on psammoma body content, and the importance of DNA flow cytometry. The advantage of FCM is that the results are simple, reproducible, and objective.

Age Factors↗
PubMed1989

Platinum complexes of triaminotriphenylmethanes: interaction with DNA and radiosensitization.

Complexes of the negatively charged tetrachloroplatinum (II) dianion and the positively charged triaminotriphenylmethane nuclear dyes, Basic Fuchsin and Methyl Green have been prepared. Elemental analysis indicated that the complexes associate as PtCl4(Basic Fuchsin)2 and PtCl4(Methyl Green) in neutral, tight ion pairs. Studies with pBR322 DNA indicated that Pt(Basic Fuchsin)2 and Basic Fuchsin produced no irreversible DNA changes, but that Pt(Methyl Green) readily and Methyl Green less efficiently produced single strand breaks in the DNA. Cytotoxicity studies in exponentially, growing asynchronous EMT6 cells in vitro showed that Pt(Basic Fuchsin)2 was more cytotoxic than Pt(Methyl Green) and that both complexes were more toxic to normally oxygenated than hypoxic cells and to cells at normal vs. acidotic pH (6.45). Radiation studies, also in EMT6 cells, demonstrated that Pt(Methyl Green) was an effective radiosensitizing drug in hypoxic cells (dose modifying factor [DMF] 1.9), but that neither the free dyes nor Pt(Basic Fuchsin)2 had significant radiosensitizing activity. In vivo studies in the FSallC fibrosarcoma confirmed the radiosensitizing properties of Pt(Methyl Green) (DMF 2.7), and indicated that Pt(Basic Fuchsin)2 also had some activity (DMF 1.4) which was equivalent to that of mizonidazole (DMF 1.4). These investigations suggest that these or similar platinum-dye complexes may have important antitumor applications in the human clinic.

Animals↗
PubMed1989

P-glycoprotein expression in treated and untreated human breast cancer.

The expression of P-glycoprotein in primary and recurrent human breast cancer was investigated by means of immunohistochemistry, using a monoclonal antibody (C219) and the streptavidin-biotin-peroxidase method. Twelve patients received no chemotherapeutic treatment. The other 11 patients were treated with chemotherapy, and all developed clinical resistance to it. No or only minimal reactivity was found in specimens coming from the untreated patients (12 cases) or from patients treated with substances not involved in the multidrug resistance phenomenon (four cases). In contrast, three out of seven tumours from patients treated with multidrug resistance related substances showed clear reactivity (positive staining in more than 20% of the tumour cells). In one of these cases, where specimens of the tumour could be studied before and after treatment, an association between the latter and expression of P-glycoprotein was suggested. Finally, this marked expression of P-glycoprotein only took place in tumours treated over a longer space of time (five courses or more of multidrug resistance related chemotherapy).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

[Proliferation index, axillary lymph node status, hormone receptors and age as prognostic factors in primary breast cancer].

A total of 233 primary carcinomas of the breast (n = 68 nodal negative and n = 165 nodal positive) of 77 woman patients of less than 50 years of age and pf 156 women patients of 50 years of age or older were examined for the prognostic significance of a proliferation index (in vitro chemoresistance assay). The prognostic significance of the proliferation index (high vs low proliferation) is compared with other prognostic factors that have already been in clinical use (age, axillary lymph node status, oestrogen and progesterone receptor status). The total median observation period was 4.8 years (3-9.1 years). Determination of the proliferation index proved to be the most important prognostic factor both for premenopausal and postmenopausal, nodal negative and nodal positive primary tumours when assessing the total survival time and the time that remains free from recurrences. A simultaneous assessment of low proliferation index and positive hormone receptor as a so-called low-risk situation shows in comparison to a high-risk situation (high proliferation index, negative receptor status) the most pronounced differences. For premenopausal women (younger than 50 years of age) the hormone receptor status has no prognostic significance as far as our group of patients is concerned, whereas for women of 50 years of age or older the receptor status is of great prognostic relevance. Besides the lymph node status, the proliferation index shows in a Cox regression model the greatest prognostic importance for the further course of a primary carcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1989

[Side effects and complications in breast-saving therapy of breast cancer].

From 1975 to June 1987, a total of 664 women underwent breast-conserving therapy for invasive carcinoma at the University Hospital for Women, Heidelberg, FRG (562 patients: surgical procedure/radiotherapy, 102 patients: only radiotherapy). A subgroup of 203 nonselected patients was prospectively followed up for complications and side effects. The population examined was representative of the entire series with reference to age distribution, tumor stage and localisation. The mean follow-up period was 28.9 months after primary therapy. Complications of breast-conserving therapy (surgery, post-operative radiotherapy, adjuvant chemotherapy for node-positive patients) were assessed by one investigator including evaluation of a standardized patients' questionnaire. The most frequent and serious single complication was lymphedema (LE) of the arm. The incidence of severe LE (greater than or equal to 3 cm difference in circumference) was 6.4%. A total of 25.1% of all patients reported some degree of swelling of the arm. The overall LE-rate was 23.1% according to the newly introduced LE-score combining the degree of difference in circumference, individual handicap and need for physiotherapy. The LE-rate was significantly increased in patients with adjuvant chemotherapy (40.1%, p less than 0.01). General impairment of arm function was reported frequently (65.6%). Shoulder mobility was severely restricted (abduction of arm less than or equal to 90 degrees) in 3.6%. Further complaints were related to impairment of fine motor function (4.5%), shielding of the arm (15.4%), reduction in absolute force (22.1%) and/or rapid tiring of the arm (37.4%). Radiotherapy related toxicity accounted for cutaneous edema (50.3%) and fibrosis of the breast (slight: 33.8%, pronounced: 9.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Epithelial growth factor receptors (EGF-R) and DNA flow cytometry in addition to lymph node and hormone receptor status as prognostic factors in primary breast cancer].

The presence of receptors for epidermal growth factor (EGF-R), the percentage of cells in S-phase and DNA-ploidy measured by flow-cytometry are new prognostic factors in breast cancer. In order to investigate the relationship between EGF-R, S-Phase/DNA-ploidy and clinical data, we measured these parameters in 68 tumors from patients with operable breast cancer. 11 Patients had positive EGF-R's (specific binding greater than 10 fmol/mg membrane-protein) and 37 patients had a positive S-Phase (more than 5% of cells in S-Phase). 10 of 44 carcinomas of ductal type were EGF-R positive, while only 1 of 18 lobular-type tumor displayed positive EGF-R's. We found significant inverse correlations between EGF-R's and estrogen receptors (p less than 0.00001) and between EGF-R's and age (p less than 0.0001): EGF-R positive tumors were found more often in young patients and in patients with estrogen-receptor-negative tumors. The EGF-R's and flow-cytometric data did not correlate with tumor size and/or nodal status. There was no correlation between EGF-R and S-Phase/DNA-ploidy in the breast cancer specimens suggesting that these two prognostic parameters are independent from each other.

Biopsy↗
PubMed1989

[Giant cell sarcoma: a rare breast tumor].

This is a case report on a giant cell sarcoma or malignant osteoclastoma of the mammarian gland. Clinical diagnosis of this very rare tumor was of an exulcerating breast carcinoma. Histologically, this tumor shows epulis-like giant cells. Pathogenetically, a metaplasia of stromal cells, and of the glandular epithelium, is discussed. A simple mastectomy with extirpation of the axillary lymph nodes was performed. No metastases were found.

Aged↗
PubMed1989

[Prognostic significance of cell kinetic parameters of endometrial cancer].

In 120 patients suffering from carcinoma of the endometrium of a wide variety of histological types, conventional clinical and morphological criteria of prognosis were compared with the DNA index (DI) and the S-phase fraction. The cellular kinetics parameters were obtained via flow cytophotometry. Adenocarcinomas (n = 101) were more frequently DNA diploid and had a lower S-phase share (less than 5%) than adenoacanthomas, clear-cell carcinomas and malignant Müller's mixed tumors. There are close correlations between the conventional prognostic factors such as FIGO stage, relative tumor invasion depth, grading and oestrogen or progesteron receptor content and the DNA content or S-phase fraction. Carcinomas with a DI less than or equal to 1.1 (n = 83) and the S-phase fraction less than 5% (n = 77), have a significantly longer survival time and recurrence-free interval than DNA-aneuploid tumors with a high S-phase fraction. The studies underline the need to use flow cytophotometry in the prognostic assessment of the carcinoma of the endometrium. The method is superior to histological grading, since the results obtained can be objectively assessed.

Aged↗
PubMed1989

Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group.

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.

Adult↗