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DNA content was measured by flow cytometry in isolated nuclei from 71 neoplastic nodules and 15 hepatocellular carcinomas isolated from rat liver at various times after treatment with an initiation—promotion regimen employing diethylnitrosamine and 2-acetylaminofluorene. Nodules and carcinomas contained mostly diploid nuclei as compared with both surrounding and normal hepatocytes which were predominantly polyploid. There appears to be a positive correlation between the degree of diploidy in nodules and their rate of proliferation. No aneuploid populations were identified in any neoplasm despite good peak resolution. These results show that an alteration in proliferation pattern from normal polyploidizing growth to diploid — diploid divisional growth is a consistent characteristic throughout the carcinogenic process in our experunental model. [ABSTRACT FROM PUBLISHER]

2-Acetylaminofluorene (AAF), given in the diet at 0.02% for 4 weeks, is an effective promoter of liver carcinogenesis initiated by partial hepatectomy (PH) plus diethylnitrosamine (DEN) in the inbred rat strain Wistar Kyoto. AAF promotes the early (6 week) appearance of phenotypically altered (γ-glutamyltranspeptidase-positive) cells as well as the later appearance of neoplastic nodules (2–4 months) and hepatocarcinomas (4–8 months). Promotion does not seem to involve selective cytotoxkity (selection of AAF-resistant hepatocytes), since neither AAF alone nor DEN+AAF has any inhibitory effect on overall liver growth. [ABSTRACT FROM PUBLISHER]

Cellular and nuclear DNA content was measured by flow cytometry and the fraction of binudeated ceDs by fluorescence microscopy in normal adult human livers, bepatoceflular carcinomas, cirrbotic livers surrounding tumors, and in some benign liver conditions. In five normal livers about one-half of the hepatocytes were polyploid; the majority of these were binudeated te-traploids containing two diploid nuclei. Thus, potyploidiza-tion in human liver does not progress as far as, for example, in the rat, where 80%-90% of adult hepatocytes are polyploid, mostly with tetraploid or octoploid nuclei. In five human euplold hepatocellular carcinomas and one investigated case of focal nodular hyperplasia, the percentage of polyplold cells was significantly reduced.. Four other carcinomas exhibited a prominent aneuplold (hypotetraplold) peak in addition to the diplold peak. An abnormally low fraction of binucleated cells was also indicated in these tumors. Liver tissue surrounding the tumors had a ploldy distribution similar to that of normal liver. The results suggest that, like In several models of experimental hepatocardnogenesis, human bepatocellular tumor growth Is associated with a decreased polyploldization tendency and a corresponding increase in diploid, divisional growth, which may give the tumors a growth advantage relative to the surrounding liver. U Nati Cancer Inst 1988;8O.148O—1485] [ABSTRACT FROM PUBLISHER]

Liver growth patterns in normal and carcinogen-treated young Wistar Kyoto rats were analyzed in terms of absolute hepatocyte numbers and ploidy distributions, calculated from DNA measurements made by flow cytometry and microscope counts of binucleated cells. Polyploidizing growth was observed during normal liver development, dominated by progressive polyploidization and a decrease in the number of diploid cells. Nonpolyploidizing growth was seen during liver regeneration and after treatment with 2-acetylaminofluorene (AAF). This mode of growth was characterized by an increase in all mononucleated ploidy classes in the absence of net polyploidization (no increase in binucleated cells). Additional diploid proliferation was detected after initiation with diethylnitrosamine followed by promotion with AAF. This selectively expanding diploid hepatocyte population, which persisted after AAF withdrawal, could represent the AAF-promoted progeny of diethylnitrosamine-altered cells with constitutive nonpolyploidizing growth properties. [J Natl Cancer Inst 1988; 80: 950–957] [ABSTRACT FROM PUBLISHER]

Background: In 2007, previous syphilis infection was diagnosed in a blood donor who had given blood regularly for 15 years. This was discovered when the donor was tested for syphilis, as a new donor in another blood bank. The time of infection is unknown. An expert group, set up by The Norwegian Directorate of Health, was commissioned to evaluate the risk of syphilis transmission through blood products in Norway., Material and Methods: The expert group based its evaluation on the epidemiology of syphilis, risk of infection and properties of the syphilis bacterium, especially in relation to blood donation. Specific information about the actual incident, made available by the Norwegian Directorate of Health, was also evaluated., Results: Of 54 blood recipients 21 were alive and 18 (86 %) were tested for syphilis, all with a negative result. For 11 deceased the hospital records were studied without discovering signs of syphilis infection., Interpretation: The risk of transfusion-transmitted syphilis is low for several reasons: The prevalence of syphilis in the population is low, a compulsory interview and completion of a questionnaire before donation in Norway excludes patients who are ill or at risk of being infected; the proportion of fresh blood donations is very low and syphilis bacteria die quickly during normal storage conditions for blood. An incidental infection is symptomatic and easily treated by antibiotics. The expert group recommends to not start syphilis testing of each blood donor but to continue the present routine testing of new donors.

Background: Chemotherapeutic treatment regimes are established for most cancer forms. In general, these substances have extremely narrow therapeutic windows, which render cancer patients vulnerable to over- and underdosing. Individual drug dosing is currently based on the patients' body surface area. This practice is an extrapolation from animal studies. Recent advances in molecular medicine raise the question of whether the present dosing strategy should be adjusted to individual functional DNA variants affecting the metabolism, transport and efficacy of anticancer drugs., Material and Methods: This review is based on selected references retrieved from PubMed and the authors' experience in drug treatment of cancer patients., Results: Several single nucleotide polymorphisms and other DNA variants that contribute to varying clinical response to chemotherapeutic agents were identified. For some drugs it has been shown that unfavourable DNA variants can lead to life-threatening side effects and/or suboptimal treatment., Interpretation: There is a compelling need for prospective, randomized studies to establish the prognostic values of pharmacogenomic markers. With few exceptions the current knowledge is insufficient to include genotype analyses in routine planning of anticancer drug treatment. In most clinical situations, individual drug dosing according to body surface area in addition to therapeutic drug monitoring and close clinical surveillance is still the preferred approach to treat cancer patients.

Background: The Norwegian Radium Hospital's sarcoma group is a multidisciplinary group with a leading role in the diagnosis and treatment of bone and soft tissue sarcomas in Norway., Material and Methods: From 1980 through 1999, 1,355 patients with soft tissue sarcoma and 458 patients with bone sarcoma were treated. In a retrospective analysis of trends over time, patients were allocated to consecutive five-year periods., Results: Patient characteristics were relatively stable, but there was an increasing proportion of soft tissue sarcomas being referred without prior surgery. Treatment principles have remained unchanged, with surgery with or without radiotherapy dominating in soft tissue sarcoma and surgery with or without chemotherapy in bone sarcoma. The amputation rate for bone sarcoma has fallen from 78% to 17%, and survival has increased significantly for both soft tissue and bone sarcoma patients., Interpretation: The results indicate significant improvements in the quality of treatment of soft tissue and bone sarcoma. More resources for treatment and organizational development of a multidisciplinary group may contribute to improved quality of care.