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Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 253 records · Page 14Linked to original sources
PubMed1992

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

PURPOSE: At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS: A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

Adult↗
PubMed1991

Limited proteolysis of the beta 2-dimer of tryptophan synthase yields an enzymatically active derivative that binds alpha-subunits.

Proteolytic modification of tryptophan synthase holo-beta 2-subunit from Escherichia coli at the C-terminal side of E-296 leads to an active species (E-296-nicked holo-beta 2) capable of interacting with alpha-subunits. Although this heterologous subunit interaction is rather weak, it induces an increase in catalytic efficiency in E-296-nicked holo-beta 2 by a factor of about 150. Correspondingly, enzymatic activity of alpha-subunits is enhanced 180-fold. This is in striking contrast to the findings from earlier reports which demonstrated that proteolytic derivatives modified at other positions in the "hinge region" embedded in the C-domain of the beta 2-subunit (K-272, R-275, and K-283) are enzymatically inactive and cannot associate with alpha-subunits. The equilibrium binding curve for the cofactor pyridoxal 5'-phosphate to E-296-nicked apo-beta 2 is hyperbolic (i.e., noncooperative), yielding an apparent microscopic dissociation constant, Kd, of 5 x 10(-6) M. This value closely resembles the low-affinity dissociation constant of cooperative cofactor binding to the native beta 2-subunit, indicating that the conformational interactions between structural domains in the modified beta-protein seem to be disturbed considerably.

Amino Acid Sequence↗
PubMed1991

Common infections in the history of cancer patients and controls.

The association between the frequency of manifest infectious diseases and cancer risk was investigated in a case-control study at Heidelberg, FRG. A total of 255 cases with carcinomas of the stomach, colon, rectum, breast, and ovary, as well as 255 population controls and 230 hospital controls were interviewed using a standard questionnaire. Controls were matched to the cases for age, sex, and region of residence at the time of the interview. A history of common colds or gastroenteric influenza prior to the interview was found to be associated with a decreased cancer risk. Thus the odds ratios for "three or more common colds per year (on average)" versus "no common cold within the last 5 years prior to the interview" were 0.18 (95% CI = 0.05-0.69) and 0.23 (95% CI = 0.06-0.89) relative to population controls and hospital controls, respectively. There was no apparent relationship between childhood infections or other diseases reported in the earlier history, and cancer risk. While the findings are supported by previous studies and fit well into the results of other fields of cancer research, a conclusive interpretation and biological explanation cannot yet be given.

Adult↗
PubMed1991

Metabolism of debrisoquine and susceptibility to breast cancer.

There may exist an association between the genetically determined oxidation status of the antihypertensive agent debrisoquine (DEB) and the propensity to develop tumours. The metabolism of DEB is extensive in 90% of healthy subjects (metabolic ratio = MR = 0-12.6; MR = % DEB excreted divided by % 4-hydroxy-DEB excreted) and poor in 10% (MR greater than 12.6). In patients with cancer of the lung, urinary bladder, and gastrointestinum, the percentage of high metabolizers is increased to greater than 98%. The poor metabolizer mode is almost devoid of cancer patients. It was investigated whether breast cancer patients show a similar association with respect to the oxidative status of DEB. 108 breast cancer patients and 123 women with benign gynecologic disorders received 1 tablet of 10 mg DEB orally in the evening. Urine was collected for the subsequent 8 hrs and analysed for its content of DEB and its main urinary metabolite 4-OH-DEB by means of HPLC. No decreased amount of poor metabolizers was seen in the cancer group.

Breast Neoplasms↗
PubMed1991

Chemoresistance in rat ovarian tumours.

In a cisplatin resistant subline (O-342/DPP) of an intraperitoneally growing transplantable rat ovarian tumour (O-342), intracellular glutathione (GSH) was approximately doubled (mean [S.E.] 1.5 [0.26] vs. 0.8 [0.2] nmol/10(6) cells). GSH reductase activity was higher (30.64 [4.07] vs. 20 [0.92] nmol/min per mg protein), although no difference was found for GSH-S-transferase. 24 h after exposure to cisplatin, formation of DNA interstrand cross-links was at a maximum in both lines and significantly higher in O-342 (162 [23] vs. 88 [22] rad eq). Combination treatment of O-342/DDP with buthionine sulphoximine plus cisplatin resulted in a marginal increase in survival compared with cisplatin treatment; treatment of this line with 3-aminobenzamide plus cisplatin was also superior to cisplatin alone. In the sensitive line both combinations were likewise superior to cisplatin alone. In vitro, at equimolar concentration, a new platinum complex (CTDP) was at least as active as cisplatin in both lines, which suggests a superior therapeutic index because its LD50 in mice is threefold higher than that of cisplatin. A ruthenium complex (ICR) had a higher activity in the resistant line. A titanium complex (budotitane) was not active.

Animals↗
PubMed1991

Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites.

29 patients with refractory malignant ascites due to metastatic peritoneal spread of adenocarcinomas originating from the ovary, gastrointestinal tract, liver, breast and uterus were treated in a phase I trial of intraperitoneal infusions of recombinant human tumour necrosis factor alpha (rhTNF-alpha). Patients received 40-350 micrograms/m2 rhTNF-alpha intraperitoneally once weekly for 2 months or for a shorter period in case of early resolution of ascites. Systemic side-effects resembled those reported for rhTNF-alpha given intravenously. No dose-limiting toxicities were found and thus a maximum tolerated dose of intraperitoneal rhTNF-alpha was not established. Out of 29 patients, 22 responded with a complete (16) or partial (6) resolution of their ascites. There was a less than 50% reduction in 4, and no increase in ascites in 1. 1 patient showed progressive ascites formation, and another patient was not eligible because of early death unrelated to treatment. Trials in patients with smaller tumour burden are warranted.

Adenocarcinoma↗
PubMed1991

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma.

Ecto-5'-nucleotidase (ecto-5'-NT) is a phosphatidylinositol anchored membrane structure recently defined as the lymphocyte differentiation antigen CD73. Using CD73 (1E9.28.1) monoclonal antibody, normal mammary gland and breast carcinoma were immunohistochemically investigated for ecto-5'-NT expression. In normal breast epithelium, CD73 was differentially expressed in lobular, ductal and myoepithelial cells and was most frequently detected in the myoepithelial compartment. The glandular stroma contained fibrocytes, a subset of which was also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9 contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts and fibrocytes showed variable degrees of CD73 expression. The extent of stromal CD73 expression correlated positively with the estrogen receptor (ER) status of the tumour (P less than 0.038). We conclude that ecto-5'-NT-expression reflects a still unknown state of activity of normal breast epithelium which is lost in the majority of carcinomas derived therefrom. It may also be indicative of some functional activity of stromal fibroblasts which is significantly enhanced in ER-positive carcinomas.

5'-Nucleotidase↗
PubMed1991

[New methods for treating surgically incomplete or inoperable recurrences of gynecologic malignancies].

Following radical or subradical surgery or an inoperable situation of recurrences of gynaecological tumours of the vaginal vault or the pelvic wall we suggest two different techniques of irradiation: 1. transtumoural afterloading-methods with a) flexible probes, and b) non-flexible probes 2. The application of iodine seeds. The objectives of these procedures are direct irradiation of the tumour or tumour-bed with limited irradiation volume, as well as the possibility of a simultaneous spacing and therefore protection of nearby pelvic and abdominal organs, which should not be irradiated and damaged. Examples of the various techniques of the distinguished operative and radiological procedures are presented.

Aged↗
PubMed1991

[Systemic therapy in recurrent and primary advanced cervix cancer].

Therapeutic results in advanced cervical cancer have not been showing any progress for more than 30 years. Only by means of systemic therapy does it seem possible, that further treatment results may be obtained similar to those in squamous cell carcinoma of the head and neck. Therefore, between 1985 and 1990 we tried to apply an aggressive polychemotherapy regimen for 5 days with cisplatinum and 5-fluorouracil with supportive treatment in 47 patients with either primary advanced inoperable (n = 25) or recurrent (n = 22) cervix carcinomas. Complete (n = 12) and partial remissions (n = 24) could be obtained in 36 out of 47 cases (= 77%). However, this high response rate conceals the fact, that this aggressive palliative treatment in case of recurrence and/or distant metastases means a considerable deterioration of quality of life with a median survival time of only 9.5 months. Although primary therapy with combined chemoradiotherapy shows good results, it is, however, only a real advantage for patients with complete response. Taking into account the short period of observation (median 25 months), the overall survival of all primary advanced cervix carcinomas is 13 + months, in case of complete remission 20 + months. It remains to be seen, whether sequential or simultaneous chemoradiotherapy will prove superior. Due to severe haematoxicity (WHO grade IV) after the first 3 treated patients, a dose reduction of 20% of chemotherapy was necessary. No further severe toxicities occurred. By means of supportive care, other side effects could also be well controlled, so that this effective polychemotherapy regimen is not only efficacious but also practicable. Prospective randomised studies are required to determine the importance of exclusive or combined chemoradiotherapy in advanced as well as in operable cancer of the cervix.

Adult↗
PubMed1991

[Lymphangiosis carcinomatosa of the skin in ovarian cancer simulating scleroderma].

Skin metastases, as the first site of manifestation of ovarian carcinoma, are very uncommon. A report on a case of dermal lymphatic carcinomatosis of the lower part of the body and the breast with the clinical appearance of scleroderma is made. Skin biopsies were performed several times and an invasion of cutaneous lymphatic vessels by carcinoma cells and psammoma bodies due to ovarian cancer was observed, which led to the correct diagnosis of ovarian carcinoma.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

[Effect of surgical procedure and adjuvant therapy on cosmetic results after breast conserving therapy in breast cancer].

A total of 207 patients undergoing breast conserving therapy (BCT, excision of tumour with clear margins, radiotherapy, sequential chemotherapy for node-positive patients) were clinically evaluated after a median follow-up of 11 months (min 2/max 22). The aim of the study was to analyse the impact of various individual factors, surgical techniques and adjuvant therapies on the cosmetic result. In 85.7% of all cases the objective outcome was satisfactory (very good: 48.8%, good: 36.9%) and in 14.3% unsatisfactory (fair: 13%, poor: 1.3%). Objective cosmetic results were rated significantly better by the patients (p = 0.01), in cases with biopsy weights of greater than 100 grms. (large/hyperplastic breast, p = 0.01), non-reconstructed mammary glands (simply closure of subcutis and skin, p = 0.01), non suction drainage of the breast (p - 0.04) and normal healing of the wound (p = 0.01). There was a trend towards better cosmetic results in the premenopause in patients with a tumour localised in the upper outer quadrant, in cases of a curvilinear as compared to a radial incision (upper/outer quadrant) and in small or average-sized breasts with biopsy weights of less than 50 grms. Cosmetic results were unaffected by a "two-step" procedure, standardised postoperative radiotherapy (45-55 Gy) and by sequential chemotherapy (3x CHT/radiotherapy/3x CHT). Unsatisfactory cosmetic short-term results should primarily be regarded as a surgical complication of BCT. Results can be improved by taking into consideration the importance of the relation of breast/biopsy-weight as well as standardising the operative procedure (curvilinear incision, closure of subcutis and skin, drainage without suction, perioperative antibiotic prophylaxis).

Adult↗
PubMed1991

[Intra-arterial chemotherapy in locally advanced breast carcinomas].

Transcatheter arterial chemotherapy with mitoxantrone was carried out in 9 patients suffering from advanced breast cancer. The anticancer agent was selectively injected in the internal mammary artery. In 2 cases the catheter was super-selectively advanced into a peripheral branch of the internal mammary artery supplying the breast carcinoma. No complication of the transcatheter treatment could be observed. CT examinations for controlling the catheter position showed perfusion of breast cancers between 40 and 90 per cent. Histological examinations of the 7 resected specimens revealed extensive necrosis in all cases. All 7 patients who underwent surgery have been without local recurrence for 3 to 12 months after treatment.

Adult↗
PubMed1991

Adjuvant therapy for breast cancer.

Different aspects of adjuvant therapy in breast cancer have been noteworthy in the past year. Evaluation of long-term results with nonspecific immunostimulatory agents in conjunction with adjuvant chemotherapy or tamoxifen have failed to show therapeutic benefit. Studies have also focused on whether tamoxifen represents an alternative to chemotherapy alone, or is more effective in combination with chemotherapy or radiation therapy.

Adjuvants, Immunologic↗
PubMed1991

The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--a 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group.

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of dexamethasone on parathyroid hormone (PTH) and PTH-related protein regulated phosphate uptake in opossum kidney cells.

Effects of dexamethasone (DEX) on receptor binding of bovine PTH (1-34) [bPTH (1-34)] and human PTH-related protein (1-34) [hPTHrP(1-34)] and cAMP accumulation, and on the inhibition of Na(+)-dependent phosphate uptake were studied in opossum kidney (OK) cells. Maximal specific binding of [125I]hPTHrP(1-34) was reduced by 40% in cells treated with 100 nM DEX, but half-maximal inhibition of binding of [125I]hPTHrP(1-34) by bPTH(1-34) or hPTHrP(1-34) was unaffected by DEX (0.5 nM and 1.4 nM, in the absence and presence of DEX, respectively). Moreover, the EC50 of bPTH(1-34) and hPTHrP(1-34)-evoked cAMP accumulation ranged from 3-7 nM and was the same with and without DEX. The EC50 of the inhibition of phosphate uptake by bPTH(1-34) and hPTHrP(1-34) ranged from 0.2-0.5 nM. Treatment with 100 nM DEX increased phosphate uptake 1.5-fold (EC50 3 nM), and the inhibition of phosphate uptake by bPTH(1-34) and hPTHrP(1-34) was suppressed. The inhibition of phosphate uptake by forskolin was also suppressed in cells treated with 100 nM DEX. DEX, on the other hand, enhanced forskolin-stimulated cAMP accumulation 1.6- to 1.8-fold. 12-O-Tetradecanoylphorbol-13-acetate did not affect cAMP production, but phosphate uptake was inhibited both in the absence and the presence of 100 nM DEX (EC50 3 nM). In conclusion, treatment of OK cells with DEX only minimally affected PTH receptor binding, and cAMP accumulation evoked by bPTH(1-34) and hPTHrP(1-34) remained unaltered. The inhibition of phosphate uptake by PTH, however, was suppressed.

Animals↗
PubMed1991

Laser palliation of locoregional recurrences of breast cancer.

The paper reports on the use of carbon dioxide and Nd:YAG lasers for palliation of locoregional breast cancer recurrences. On the basis of three case reports, pros and cons of laser assisted treatment of loco-regionally recurrent breast cancer are discussed. A carbon dioxide--Nd:YAG combination therapy is proposed as the method best suited. The preliminary results indicate that laser palliation of local relapse and soft tissue metastases might enlarge the therapeutic spectrum.

Aged↗