Biochemical short-term predictive assay: results of correlative trials in comparison to other assays.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Kaufmann.
Explore the source record for details and available documents.
This study compares the two oxazaphosphorine compounds ASTA Z 7557 (AZ) and cyclophosphamide (CP) in their therapeutic activity as well as in their myelotoxicity and DNA damage being induced after a single intraperitoneal injection. Therapeutic activity was determined towards methylnitrosourea-induced rat mammary carcinomas in vivo and in vitro, resulting in comparable efficacy of both compounds at their optimal doses, respectively, with the sensitivity of individual tumors being reflected by the degree of inhibition of 3H-thymidine uptake of these cells in vitro. Myelotoxicity was measured as inhibition of pluripotent (CFU-S) and macrophage-granulocyte committed (CFU-C) stem cells together with the extent of single strand breaks and DNA-DNA interstrand crosslinks in murine bone marrow. At equimolar base AZ was found to induce a higher level of DNA damage than CP in the bone marrow of mice 16 hours after a single intraperitoneal injection. Both compounds depressed the pluripotent stem cell compartment of the bone marrow to a similar extent, whereas AZ was significantly less toxic to the granulocyte cell lineage.
Adjuvant chemotherapy should be conducted at present only under controlled conditions ("studies") with the consent of the patient after supplying her with adequate information ("informed consent"). The most important prognostic factor in primary carcinoma of the breast is the axillary lymph node status. The decisive role with regard to determining the further course of action and mapping out the treatment strategy will be played by the operating surgeon and the pathologists. Adjuvant chemotherapy can prolong the relapse-free survival time for all prognostic sub-groups known so far (the differences, however, are not significant in every case). It is very probable that the total survival rate will be improved for certain sub-groups. The effectivity of adjuvant chemotherapy decreases with increasing involvement of the lymph nodes. Pre-menopausal patients with one to three affected lymph nodes presently derive the biggest benefit from adjuvant chemotherapy. Short-term chemotherapy (up to 6 months) will suffice. The optimal treatment period is not yet known. The aggressivity of the adjuvant chemotherapy chosen for a particular case is of absolutely paramount importance. Provided the dosage is the same for both groups, there is no evidence of any clear difference between pre-menopausal and post-menopausal patients. It seems, however, that the quantitative reduction of the relapse rate is greater with pre-menopausal patients. Onset of chemotherapy should be as early as possible after surgery (14th postoperative day). A dosage schema should be followed according to calculated full dosage, if possible via the intravenous route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The histologic grading especially of the modified Broders'-Grading is a suitable prognostic factor in Ovarian Carcinoma. Our investigations show this to be especially true after failure with first line chemotherapeutic agents. These morphologic gradings should especially be used for the selection for high risk patients and for the treatment planning in ovarian carcinoma.
A total of 156 patients with metastatic breast cancer were entered into a prospective multi-center trial in September 1975. All patients were treated monthly with vincristine, adriamycin and cyclophosphamide (VAC) six times, followed by 5-fluorouracil, methotrexate and cyclophosphamide (FMC) until progression was documented. By random assignment, the patients received 5 mg/m2 Corynebacterium parvum (CP) subcutaneously on day 1, in addition to VAC/FMC. Of the 150 evaluable patients, 33 of 76 (45%) and 36 of 74 (49%) had complete or partial response to VAC/FMC plus CP, respectively. The Kaplan-Maier curves of duration of remission and survival were almost identical (medians 14.5 vs 12.1 months and 22.2 vs 21.1 months, respectively). The hematologic and gastrointestinal toxicity were also similar in the two study groups. However, 19 of 74 (26%) patients developed skin ulcers after repeated injections of CP. These patients showed prolonged survival (P = 0.002, log rank test). These results suggest that adding nonspecific immunostimulation with CP to currently available chemotherapy on day 1 is of no benefit to most patients with metastatic breast cancer, but may select an "immunoreactive subgroup with increased local toxicity and survival.
The antigen-induced leukocyte adherence inhibition (LAI) test is an assay of cellular immune reactivity which was expected to offer a promising adjunct to currently available diagnostic and monitoring procedures in cancer patients. We have applied this assay to (1) 83 inpatients clinically suspected of having breast cancer, (2) 50 out-patients before mammography, and (3) 37 healthy women. In order to account for the known heterogenicity of breast cancer, we performed LAI assays with extracts from 15 primary tumors of known and 14 primary tumors of initially unknown histology. Thus, the problem of tumor specificity in the LAI assay was tackled in a double-blind fashion. The results obtained clearly show that breast-tissue-specific rather than tumor-specific responses were detected by LAI testing. The LAI assay failed to discriminate between high-risk patients with and without cancer and between extracts from breast tumors with and without carcinoma. The results are discussed with regard to the many claims for the detection of specific tumor immunity in the literature.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Well-defined and individualised chemotherapy of human malignant tumours can be initiated with the aid of sensitivity tests for chemotherapeutic agents prior to treatment. The effectiveness of the specific cytotoxic agent can be determined by sensitivity testing. For these investigations three methods are available at present: 1. a short-term incubation method (biochemical assay). 2. an agar-cloning assay as a specific tissue culture method and 3. a heterotransplantation method with transplantation of tumour cells into thymus-aplastic animals. For routine clinical testing only the biochemical short-time assay and the agar colony assay are of practical significance. The test rates and growth rates in the two methods are composed. The in-vitro and in-vivo correlations of sensitivity testing of chemotherapeutic agents and resistance to chemotherapeutic agents in the different test systems show that the accuracy of prediction for the correct positive or correct negative result is 90%. These results are based on retrospective analysis. For the evaluation of the different prediction assays and for the evaluation of the clinical application of these methods only a randomised prospective therapeutic study can give the answers. However, this has not yet been carried out to date.
Two cases of carcinomatous meningeosis are reported. One occurred during cis-platinum combination treatment (PAC-scheme) for advanced ovarian carcinoma and one during the same treatment for a carcinoma of the cervix. Both patients showed no neurological problems prior to chemotherapy. The central nervous symptoms developed rapidly following the administration of small doses of cis-platinum (total dose 160 or 300 mg) and could not be controlled. In one case tumour cells were found in the cerebral spinal fluid. The cause of death could have been an unusually toxic reaction to cis-platinum. A thorough neurological examination prior and during chemotherapy with cis-platinum is necessary in order to recognize toxic side effects of the drug as soon as possible.
Primary breast cancer tissue and lymph nodes were obtained from 55 patients, Histologically, 34 of these patients had positive and 21 negative lymph nodes. Estrogen receptors (ER) and progesterone receptors (PR) were determined by a dextran-coated charcoal assay. The tumor tissue was ER positive in 58% of the cases and PR positive in 34%. The malignant lymph nodes were ER positive in 56% and PR positive in 24%. ER in 14% and PR in 5% of the benign lymph nodes could be detected. The primary tumor tissue and the corresponding malignant lymph nodes showed an identical ER and PR status, i.e. both tumor sites were receptor positive or both receptor negative, in 68 and 74%, respectively. However, 21% of the patients had receptor-positive tumors but receptor-negative lymph nodes. Receptor-positive lymph nodes in combination with receptor-negative tumors occurred in only 11% for ER and 6% for PR. These data show that receptor-positive malignant lymph nodes mostly display the same receptors status as the corresponding primary tumor, whereas receptor-negative lymph nodes may be combined with receptor-positive tumors.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Data from literature as well as our own studies are used in the discussion of differential diagnosis of the so-called endodermal sinus tumours. Clinical and paraclinical aspects of this once lethal tumour species are reported. New therapeutic strategies are presented consisting of the introduction of new, effective combinations with adjuvant chemotherapy. Thus at early stages a conservative surgical approach seems to allow the preservation of fertility in these generally young women. But even in more advanced cases the administration of a modern adjuvant polychemotherapy is likely to result in higher survival rates.
Immunoreactive calcitonin (CT), indistinguishable from human CT-(1-32) and its sulfoxide, has been identified in extracts of the hypothalamus, the pituitary, and the thyroid obtained from human subjects at autopsy. DCT concentrations were highest in a region encompassing the posterior hypothalamus, the median eminence, and the pituitary; intermediate in the substantia nigra, the anterior hypothalamus, the globus pallidus, and the inferior colliculus; and low in the caudate nucleus, the hippocampus, the amygdala, and the cerebral and cerebellar cortices. Specific CT binding measured with 125I-labeled salmon CT was highest in homogenates of the posterior hypothalamus and the median eminence, shown to contain the highest concentrations of endogenous CT in the brain; CT binding was less than 12% of hypothalamic binding in all of the other regions of the brain examined and was negligible in the pituitary. Half-maximal binding was achieved with 0.1 nM nonradioactive salmon CT-(1-32), and the binding was directed to structural or conformational sites, or both, in the COOH-terminal half of salmon CT. The rank order of the inhibition of the binding by CT from different species and analogues of the human hormone was the same as in receptors on a human lymphoid cell line (Moran, J., Hunziker, W. & Fischer, J. A. (1978) Proc. Natl. Acad. Sci. USA 75, 3984-3988). The functional role of CT and of its binding sites in the brain remains to be elucidated.