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Biomedical subjects

D Killander

Publications and source records attributed to D Killander.

At least 55 records · Page 3Linked to original sources
PubMed1990

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Adolescent↗
PubMed1989

Prognostic value of steroid receptor concentration and flow cytometrical DNA measurements in stage I-II endometrial carcinoma.

In order to make a more individualized therapy possible in endometrial cancer we investigated the prognostic ability of steroid receptor concentration and the DNA content in individual cells as measured by flow cytometry. We found that although the steroid receptor concentration was a prognostic parameter, the DNA content proved to be a better parameter than all other known prognostic parameters in endometrial carcinomas stage I-II. Thus it was possible to divide the tumors into three groups; 1) diploid tumors with a relapse rate of 6%, 2) aneuploid tumors with a high estradiol receptor concentration and without myometrial invasion of more than the inner third, and with a relapse rate of 18%, 3) aneuploid tumors, poorly differentiated with a low estradiol receptor concentration or myometrial invasion and with a relapse rate of 44%.

Adult↗
PubMed1989

Flow cytometry DNA ploidy and number of cell populations in the primary breast cancer and their correlation to the prognosis.

In a prospective study on 516 breast cancer patients flow cytometry DNA ploidy and number of cell populations (defined as number of DNA stem lines) detected in the primary tumor were evaluated for prognostic purposes. The median follow-up time was about 5 years. In the 241 node negative cases, those patients with three or more cell populations had the worst prognosis, with a distant recurrence-free survival rate of about 60% at five years compared to 90% in cases with only one cell population detected in the primary tumor. The number of tumor involved axillary lymph nodes was the outstanding prognostic indicator which was confirmed in 275 node positive patients; DNA ploidy and number of cell populations did not give any significant prognostic information in this group of patients.

Antineoplastic Agents↗
PubMed1987

Aspiration of musculoskeletal tumors for cytodiagnosis and DNA analysis.

Preoperative fine-needle aspirates of 25 soft tissue tumors and four bone tumors were used for cytodiagnosis and flow cytometric DNA ploidy analysis. The results were compared with the histopathologic diagnosis and flow cytometric DNA ploidy analysis on tissue samples after surgery. There was good agreement between the cytodiagnoses and histopathologic diagnoses with regard to benign tumor or sarcoma. There was good agreement between the ploidy determinations in aspirates and tissue samples in 20 out of the 26 tumors that could be analyzed. Aneuploid cell populations were found in 13 tumors cytologically classified as sarcoma and in one tumor classified as unspecified malignant tumor. These 14 tumors also showed aneuploid cell populations in the tissue samples and were histologically diagnosed as high-grade malignant sarcomas. The combined evaluation of preoperative cytodiagnosis and DNA ploidy on aspirates may give valuable prognostic information.

Adult↗
PubMed1986

Simultaneous immunofluorimetric quantitation of IgM and IgG in single splenic lymphoid cells after immunization.

The amount of IgM and IgG was determined in individual mouse spleen lymphocytes by double immunofluorimetry after "staining" with dimethylamino-naphthaline sulfonyl chloride-labeled anti-IgM and fluorescein isothiocyanate-labeled anti-IgG. During a single immune response against sheep erythrocytes there was an inverse relationship between the amounts of these two immunoglobulins in individual cells. There was an early steep increase of the cellular amount of IgM during the first 3 days after immunization. Subsequently IgG increased exceeding the initial IgG levels while IgM decreased. Most cells containing high amounts of IgM had a low IgG content and vice versa. The present results directly demonstrate a quantitative switch from IgM to IgG in individual cells on the single cell level after an antigenic stimulus. This indicates simultaneous active production of both immunoglobulins in these cells. For an explanation of this phenomenon differential mRNA splicing rather than DNA rearrangement as an underlying process for immunoglobulin expression may be proposed in these early B-cells.

Animals↗
PubMed1984

Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck after mitomycin C and cisplatin treatment.

Cell kinetic studies are of interest for clarifying the concepts of chemotherapeutic strategy in the multimodality therapy of advanced squamous-cell carcinoma of the head and neck. A poorly-differentiated squamous-cell carcinoma of the head and neck heterotransplanted to nude mice was used for analyses of chemotherapeutically induced cell cycle perturbations. The heterotransplanted tumour, in its 15th or later passages in nude mice, was treated with either Mitomycin C or cisplatin. After determination of dose-response relationships and toxicity, treated tumours were biopsied at different times and cell cycle distribution pattern, 3HTdR incorporation into DNA, histology and tumour volume were recorded. Mitomycin C and cisplatin gave the same pattern of cell cycle perturbations, although the changes induced by cisplatin were more profound. There was an initial increase of the fraction of cells in the S phase, concomitant with a reduction of the fraction of cells in G0 + G1 phase. When these perturbations were normalized a transient increase of the fraction of cells in G2 + M phase was observed. However, while cisplatin caused an initial transient depression of DNA synthesis, the Mitomycin-C-treated tumours exhibited a short-lasting increase of DNA-synthesis. The maxima of the induced changes in cell cycle phase distribution and DNA-synthesis lasted for only 24-48 h, which may be of importance for scheduling combinations of drugs. Though both drugs induced profound changes in tumour volume growth and cell kinetics, there was no change in the histopathological picture of the treated tumours. Routine histopathological examination is thus not likely to be of value evaluating the effect of chemotherapy.

Animals↗
PubMed1984

Flow-cytometric DNA analysis in primary breast carcinomas and clinicopathological correlations.

Flow-cytometric DNA analyses of single cell nuclei were performed on nuclear suspensions prepared from biopsies of primary breast carcinomas in 638 patients. Propidium-iodide-stained cell nuclei were analysed in an Ortho 50-H Cytofluorograph. The patients were staged by the TMN classification. Sixty percent of all the patients had aneuploid primary breast carcinomas; of size T1, T2, T3, and T4 tumors, 51%, 63%, 67%, and 75% were aneuploid, respectively. The proportions of aneuploid tumors in each of the tumor stages SI, SII, SIII, and SIV were 47%, 62%, 67%, and 69%, respectively. This trend to increasing aneuploidy proportions with more advanced disease was significant in contrast to the degree of aneuploidy found in relation to axillary nodal tumor involvement. Multiple aneuploid cell populations were found in 109 (17%) tumors. With a mean follow-up time of 16 months, 92 patients have relapsed out of 540 completely staged patients with unilateral breast cancer with no distant metastases at the time of initial treatment. When the influence of various treatments and tumor stage are not considered, the recurrence rate was twice as high among patients with aneuploid primary tumors than among patients with euploid tumors. The differences in relapsing rates among patients with euploid and aneuploid primary tumors decreased with more advanced disease. Out of 170 patients with T1 tumors, 17 relapsed and 16 of these were aneuploid. No such difference in relapse rate in relation to ploidy was, however, found in patients with more advanced primary disease.

Adult↗
PubMed1984

Prediction of survival in breast cancer. Principles and current status of hormone receptors and DNA content as prognostic factors.

The probability of survival in breast cancer patients is the net result of a number of factors. The presence of distant metastases, mostly occult, the size and growth rate of the systemic tumour burden and causes of mortality other than breast cancer are major determinants of the outcome after primary treatment. We emphasize the need for separating these different options as a prerequisite for individualized primary treatment and follow-up and also for a rational selection of patients for adjuvant therapy. Several lines of evidence suggest that the oestrogen receptor (ER) content reflects the growth rate of the tumour cells rather than their proneness to metastasize. A high ER content in the primary tumour would accordingly predict an extended disease-free survival and a relatively long survival after relapse rather than a low ultimate frequency of distant disease and mortality. Available data indicate that the progesterone receptor concentration extends--and possibly replaces--this prognostic implication of ER. Analyses of the clinical course in relation to the DNA content of the tumour cells are still at an early stage, but preliminary results point to a poorer prognosis in aneuploid than in euploid tumours, especially among patients with breast cancer of an early stage. It remains to be established, however, whether the distribution of the nuclear DNA content is mainly an expression of tumour growth rate or whether it is also an indicator of metastatic potential, and thus of long-term survival; and if so, whether it has this capacity independently of established prognostic factors such as axillary node status, tumour size and morphological characteristics.

Breast Neoplasms↗
PubMed1983

Relationship between the amounts of EBV-DNA and EBNA per cell, clonability and tumorigenicity in two ebv-negative lymphoma lines and their EBV-converted sublines.

The effect of EBV-conversion of two EBV-negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between 1.1 and 4.9 times compared to the original "parental" lines. Tumorigenicity was increased in one out of 2 BJAB-derived, EBV-positive lines and in 3 of 6 Ramos-derived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV-genomes/cell, the amount of EBNA/cell and tumorigenicity.

Animals↗
PubMed1982

Expression of theta antigen on mouse thymocytes during the cell cycle.

Cells from normal mouse thymus were subdivided according to size and analysed for surface antigen expression, protein content and DNA expression and content. It could be shown, that the expression of theta-antigen followed protein accumulation in individual cells. Protein content on the other hand, was correlated with DNA synthesis even if it varied over a greater range. Only one subgroup of small non-DNA-synthesizing cells was calculated to have a higher density indicative of a more condensed state together with an increased surface antigen content. These cells might represent the G0 state of the remnant proliferating population and most resembled the small cortical cells.

Animals↗
PubMed1982

Treatment of chronic lymphocytic leukaemia and well-differentiated lymphocytic lymphoma with continuous low- or intermittent high-dose prednimustine versus chlorambucil/prednisolone.

Prednimustine, a new antitumour drug, is a chlorambucil ester of prednisolone. The present prospective randomized study compares the effect of continuous low-dose (B) and intermittent high-dose (C) prednimustine in previously untreated patients with progressive CLL and WDLL. The control group received continuous chlorambucil/prednisolone therapy (A). One hundred and eighteen patients, 88 CLL and 30 WDLL, were evaluable. Response to therapy (greater than 50% improvement) was noted in 61, 55 and 57% in groups A, B and C respectively. The difference was not statistically significant. Time to response, response duration and survival did not show any differences between the groups. Responding patients survived longer than patients with stationary and progressive disease. Median survival time was 72 months from diagnosis and 52 months from start of therapy, with no differences between the treatment groups. Toxicity of prednimustine was usually mild and similar to that of the two constituents. Treatment schedule C showed a slight advantage with regard to frequency of side effects. In conclusion, in this study the therapeutic effect of prednimustine was equal to that of its constituents administrated separately.

Adult↗
PubMed1980

Decreased density in membrane localized macromolecules in cells enlarged after X-irradiation or polyploidization.

Cytophotometric measurements of DNA, dry mass (total proteins) and surface localized IgM and Ia were performed on individual cells of a Burkitt lymphoma derived cell line after X-irradiation and after polyploidization. Blockage of cell division was achieved with 250 r, and an arrest in G2 was found 48 hr after irradiation. The cells unable to divide increased in volume and total protein content. Cell enlargement was also achieved by polyploidization. The amount of surface localized IgM and Ia did not keep up pace with the increase in total proteins, thus their density decreased. This was reflected in decreased sensitivity of the enlarged cells to the cytotoxic effect of specific antisera.

Cell Line↗
PubMed1980

DNA and its synthesis in individual tumor cells from human upper respiratory tract squamous cell carcinomas.

Measurements of cytophotometric Feulgen DNA content and incorporation of 3H-thymidine were made in individual tumor cells from 58 patients with squamous cell carcinomas of the head-neck region. These measurements were correlated with a point ranking system for pathological grading for these types of tumors. Two of the parameters of the grading system, mode of invasion and nuclear polymorphism which had been found to be important factors in prognosis in clinical studies were correlated to the objective cellular DNA measurements. In 40 carcinomas, 10 were found to have a predominantly diploid distribution of DNA values, while the remaining 30 tumor values were either multiples of diploid or were aneuploid. Generally, tumors with low point rankings for individual morphological parameters tended to have diploid DNA values. Those tumors with higher DNA values usually had larger point rankings and more advanced clinical stage. When tumor cells from biopsies of 39 patients were studied by 3H-thymidine incorporation, no relevant connections between the labeling index and cellular DNA amounts, malignancy grading, or clinical stage were found.

Carcinoma, Squamous Cell↗
PubMed1979

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Aged↗
PubMed1978

Prognostic factors in Hodgkin's disease. II. Role of the lymphocyte defect.

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or decreased from Hodgkin's disease. Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8). All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.

Adolescent↗