Search PubMed⌕ Search

Biomedical subjects

R Lewensohn

Publications and source records attributed to R Lewensohn.

At least 73 records · Page 4Linked to original sources
PubMed1983

Inhibition of nitrogen mustard induced DNA repair synthesis by anthracyclines in human peripheral leukocytes.

DNA repair synthesis was induced by nitrogen mustard in human peripheral leukocytes. When the cells were treated with increasing doses of doxorubicin or daunorubicin a decrease of the DNA repair synthesis was recorded. Daunorubicin had a significantly higher inhibitory effect on the DNA repair synthesis compared to doxorubicin. The inhibitory effect by doxorubicin or daunorubicin on nitrogen mustard induced DNA repair synthesis was compared with the inhibitory effect on replicative DNA and RNA synthesis in human lymphoblasts. The inhibition of DNA repair synthesis was significantly lower than the inhibition of replicative DNA synthesis and RNA synthesis for both drugs.

Cells, Cultured↗
PubMed1982

DNA-repair synthesis in blast cells from patients with acute myeloblastic leukaemia.

DNA-repair synthesis was studied in blast cells from patients with acute myeloblastic leukaemia. The DNA-repair synthesis, measured as 3H-thymidine incorporation, was registered as unscheduled DNA synthesis by autoradiography, and also after suppression of the replicative DNA synthesis by hydroxyurea by liquid scintillation. There was good correlation when results from both methods were compared. A significantly wider variation of unscheduled DNA synthesis was found in leukaemic as compared to normal blast cell populations. There was also a wider variation within individual leukaemic blast cell samples compared to normal samples. A correlation was found between unscheduled DNA synthesis induced by nitrogen mustard and by UV-irradiation in the leukaemic blast cell populations. The UV-induced unscheduled DNA synthesis in some of the leukaemic blast cell populations continued to increase at doses of UV-irradiation at which normal myeloblasts had reached their maximum level of unscheduled DNA synthesis. This indicates that at least some malignant blast cell populations may possess an effective DNA-repair system.

Alkylating Agents↗
PubMed1982

DNA repair synthesis in subpopulations of human lymphocytes.

Human peripheral blood lymphocytes enriched in T or B cells were exposed to ultraviolet irradiation, nitrogen mustard or methylmethane sulphonate and investigated regarding their capacity for DNA repair synthesis. The DNA repair synthesis, measured as [3H] thymidine incorporated, was determined by autoradiography as unscheduled DNA synthesis (UDS). No systematic difference could be found in the capacity for UDS between the T- and B-cell-enriched fractions. A larger individual variation in UDS was found in the B-cell- compared to the T-cell-enriched lymphocytes.

B-Lymphocytes↗
PubMed1982

Different activities of unscheduled DNA synthesis in human melanoma and bone marrow cells.

Unscheduled DNA synthesis (UDS) indicated by melphalan was studied in freshly collected tumor cells from human melanoma metastases. Comparative studies were done on human bone marrow blast cells. Significant levels of UDS comparable with those in myeloblasts were found in only two of eight melanoma cell populations. This difference between melanoma and blast cells was not related to different cellular uptake of melphalan. When UDS was induced by ultraviolet irradiation, significant levels of UDS were found in all melanoma and blast cell populations studied. Also, in a human melanoma cell line, high levels of UDS were found after exposure to ultraviolet irradiation, while treatment with melphalan did not result in detectable levels of UDS. Possible explanations for the divergent results of UDS in melphalan-exposed melanoma cells are discussed.

Bone Marrow↗
PubMed1982

Flow cytofluorometric DNA analyses of metastases of human malignant melanomas.

Flow cytofluorometric analyses of DNA content were performed on 38 subcutaneous and lymph node metastases from 32 patients with malignant melanoma. Cells from 8 tumors had DNA patterns corresponding to diploid DNA values, and the remaining 30 had aneuploid cell populations, mostly in the diploid to tetraploid region. Eight tumors contained more than one cell population. The number of S-phase cells varied from 3% to 34%. The number of S-phase cells was significantly higher in aneuploid as compared to diploid cell populations. Patients with a proportion of S-phase cells greater than or equal to 10% had a significantly shorter survival time as compared to patients with less than 10% S-phase cells.

DNA, Neoplasm↗
PubMed1981

Decreased UV-induced DNA repair synthesis in peripheral leukocytes from patients with the nevoid basal cell carcinoma syndrome.

The UV-induced DNA repair synthesis in peripheral leukocytes from 7 patients with the nevoid basal cell carcinoma syndrome was compared to that in peripheral leukocytes from 5 patients with basal cell carcinomas and 39 healthy subjects. A dose response curve was established for each individual, and maximum DNA repair synthesis was used as a measure of the capacity for DNA repair. The patients with the nevoid basal cell carcinoma syndrome had about 25% lower level of maximum DNA repair synthesis as compared to the patients with basal cell carcinomas and control individuals. The possibility that DNA repair mechanisms may be involved in the etiology to the nevoid basal cell carcinoma syndrome is discussed.

Adult↗
PubMed1981

Human monocytes and lymphocytes differ in the rate of DNA repair synthesis and viability after exposure to nitrogen mustard.

Unscheduled DNA synthesis was studied in human lymphocytes and monocytes after treatment with nitrogen mustard, methyl-methane-sulphonate and ultraviolet irradiation. The unscheduled DNA synthesis was about 4 times higher in monocytes than in lymphocytes after treatment with nitrogen mustard. Treatment with methyl-methane-sulphonate or ultraviolet irradiation confirmed the higher capacity for unscheduled DNA synthesis in the monocytes. When Ficoll-Isopaque-isolated mononuclear cells were exposed to various doses of nitrogen mustard and incubated for different periods, a dose- and time-dependent increase in trypan blue uptake was found. Furthermore, a corresponding dose- and time-dependent decrease was noted in 3H-uridine incorporation. Since trypan blue uptake will not enable differentiation between monocytes and lymphocytes appearing as a mixed cell population, 3H-uridine flash labeling index was studied after exposure to nitrogen mustard. There was a dose- and time-dependent decrease in 3H-uridine labeling index, suggesting a correlation between the absence of 3H-uridine incorporation and increase in trypan blue uptake. When compared to monocytes, the lymphocytes were more affected in this respect after exposure to nitrogen mustard. The possibility that differences in cytotoxic effect may be related to DNA repair mechanisms is discussed.

DNA↗
PubMed1981

An EBV-associated, Swedish case of Burkitt-type malignant lymphoma.

Morphological, serological, DNA-homology and immunofluorescence studies of a rapidly fatal malignant lymphoma in a 25-year-old Sweden male revealed most of the characteristics of an EBV-associated Burkitt lymphoma. The various findings are discussed in relation to previously reported observations on endemic (African) and non-endemic Burkitt lymphomas.

Adult↗
PubMed1980

Induction of unscheduled DNA synthesis in human myeloma cells.

Unscheduled DNA synthesis (UDS) induced by melphalan, nitrogen mustard and ultra-violet irradiation was studied in bone marrow cells from myeloma patients. In a previous study, normal bone marrow cells in various stages of maturation were found to display a gradual decrease in UDS parallel with the process of maturation. Myeloma cells showed a similar pattern. Poorly differentiated myeloma cells exhibited a similar level of UDS to myeloblasts and erythroblasts. Irrespective of which repair-inducing agent was used, the relationship between the levels of UDS in the various cell types was constant. This indicates that the differences in the level of UDS in the various cell types was not due to differences in the uptake of the repair-inducing agent.

Alkylating Agents↗
PubMed1979

Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of various cell populations disclosed considerable differences in their UDS level, this generally being greatest for the blast populations. During maturation of both myelopoietic and erythropoietic cells, there was a decrease in the UDS level, which was lowest for the end-cell stage. The lymphocytes and monocytes differed considerably in their capacity for UDS. The developed technique would appear to offer an opportunity for determining the capacity for DNA-repair synthesis in malignant bone marrow cells, a factor that has been linked to sensitivity to alkylating agents.

Alkylating Agents↗
PubMed1978

Factors responsible for bone marrow toxicity after treatment of myeloma patients with different alkylating agents.

Leukopenia and thrombocytopenia were studied after loading doses of melphalan (5 mg/daily for 18-25 days) in 71 myeloma patients. Seventy per cent of the patients developed pronounced leukopenia (white cells less than 2.0 X 10(9)/l) and/or thrombocytopenia (platelets less than 100 X 10(9)/l). The patients with pronounced and moderate hematological side-effects, respectively, were compared for weight and age. The body weight was the same in the two groups, indicating that the patient's weight is of minor importance for the dosage of melphalan. There was a numerical difference in age, on the borderline for statistical significance, indicating that the age of the myeloma patient may be of minor importance for the dosage of melphalan. It is possible that more pronounced age differences may be of greater importance in this respect. Fifteen patients with myeloma were treated with cyclophosphamide. Compared with melphalan, the effect on white cells was the smae, while the incidence of thrombocytopenia was statistically significantly lower with cyclophosphamide.

Aged↗
PubMedDate not supplied

Pathologic complete remission after preoperative intracavitary radiotherapy of cervical cancer stage Ib and IIa is a strong prognostic factor for long-term survival: analysis of the Radiumhemmet data 1989-1991.

The purpose of this study was to evaluate the treatment results of preoperative brachytherapy and the prognostic value of pathologic complete remission after preoperative intracavitary irradiation in patients with stage Ib and IIa cervical carcinoma in relation to recurrence rate and survival. The clinical records of 185 patients with stage Ib (129 patients) and IIa (56 patients) cervical carcinoma, consecutively admitted to Radiumhemmet from January 1989 to December 1991 were reviewed. The median follow-up time was 71 months. In 121 patients the treatment consisted of uterovaginal intracavitary irradiation, according to the Stockholm technique, followed by surgery. Tumor remission assessed in the surgical specimen was classified as pathologic complete remission (pCR) if no microscopic tumor was found or incomplete pathologic remission (non-pCR) if microscopic residual tumor was found. Postoperative external beam radiation was added to cases with metastases in pelvic nodes or residual tumor in the resection margins. The disease-specific 5-year survival was 87% and 75% for stage Ib and IIa, respectively, for the patient population treated with preoperative intracavitary radiotherapy and surgery. After intracavitary radiation, 79% of the patients obtained pCR of the primary tumor. Five-year survival in those with pCR was 95%, compared with 46% in those with non-pCR (P < 0.0001). Patients with pCR and no lymph node metastases had a 98% 5-year survival as compared to a 5-year survival of 64% in patients with non-pCR and node negativity (P < 0.0001). Locoregional relapses were diagnosed in 2% of the patients with pCR compared to 54% in patients with non-pCR (P < 0.0001). Multivariate analysis revealed non-pCR (RR = 6.42) and node positivity (RR = 4.59) as nonfavorable factors for survival, while tumor size was not found to be of independent significance for survival. Pathologic complete remission after intracavitary irradiation is a strong favorable prognostic factor in node-negative patients. The combination of preoperative intracavitary radiotherapy and surgery results in a high cure rate and aids in identifying patients at risk for relapse who might be subject to adjuvant therapy.

Brachytherapy↗
PubMedDate not supplied

Expression and activity of DNA-dependent protein kinase in normal human leukocytes.

BACKGROUND: DNA-PK is a serine/threonine protein kinase that has been shown to play an important role in V(D)J recombination, Ig switching and DNA double strand break (DSB) repair. We have investigated DNA-PK in whole cell extracts from B and T lymphocytes, monocytes and granulocytes and the effects of phorbolmyristate acetate (PMA) and Concanavalin A (Con A) on DNA-PK in B and T lymphocytes. MATERIALS AND METHODS: Lymphocytes were separated from human peripheral blood using the E-rosette technique and DNA-PK was analysed using Western blot, DNA-PK kinase activity assay and flow cytometry. RESULTS: The levels of DNA-PK activity and content varied among the leukocytes. PMA and Con A stimulation consistently increased both DNA-PK activity and content in B lymphocytes as cells entered the S phase. Up-regulation could normally not be seen in T lymphocytes, although cells entered the S phase following PMA and Con A stimulation. CONCLUSION: Mitogenic stimulation up-regulates DNA-PK activity and protein expression in B lymphocytes. T lymphocytes show interindividual differences in DNA-PK. Regulation of DNA-PK is not strictly cell cycle dependent for all cell types.

Adult↗
PubMedDate not supplied

Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival.

BACKGROUND: Human papilloma virus (HPV), which is frequently present in tonsillar carcinoma seems to be a prognostically favourable factor for patient survival and also for low risk of relapse. Since HPV may abrogate the function of wild type p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53 status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and patient survival. MATERIALS AND METHODS: Pre-treatment primary tonsillar carcinoma specimens were obtained retrospectively from 40 patients, 21 complete responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage III and IV tumours. The paraffin-embedded biopsies were analysed for presence of HPV DNA, by general and type specific PCR, and for p53 overexpression by immunohistochemical staining with the murine Mab DO-1. RESULTS: It was possible to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53 immunostaining (p53+) were not correlated with response to RT, since 8/18 CR patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR patients were p53+. A tendency towards a survival benefit in patients with HPV+ tumours was observed and this tendency was significant for patients with stage IV HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A difference in survival between patients with p53+ cancer as compared to patients with p53- lesions was not demonstrated. In conclusion, although presence of HPV and p53 immunoreactivity in tonsillar carcinoma could not be related to RT response, determination of HPV and p53 status may still prove useful as predictive/prognostic markers.

Biomarkers, Tumor↗
PubMedDate not supplied

Cytotoxicity and DNA cross-linking induced by peptide conjugated m-L-sarcolysin in human melanoma cells.

Peptichemio is a complex of six peptides containing m-L-sarcolysin which is used in cancer chemotherapy. One of the peptides, L-propyl-m-sarcolysyl-L-p-fluorophenylalanine (PSF), is highly toxic to melanoma cells. We have compared the effects of melphalan, m-L-sarcolysin and PSF on human melanoma cell lines. PSF was 35-fold and 28-fold more toxic to RPMI 8322 melanoma cells than melphalan and m-L-sarcolysin, respectively. Similar differences in the cytotoxic effects of PSF and m-L-sarcolysin were also seen with two other melanoma cell lines. The cytotoxicity of both PSF and m-L-sarcolysin to RPMI 8322 melanoma cells was potentiated by depletion of cellular glutathione. Both PSF and m-L-sarcolysin caused a protracted induction of DNA cross-links in RPMI 8322 cells, with maximum at 24 hours after drug exposure. PSF induced 9-fold higher levels of DNA interstrand cross-links than m-L-sarcolysin, indicating that the increased cytotoxicity of this drug is associated with a more efficient induction of DNA damage.

DNA, Neoplasm↗