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Biomedical subjects

G Saeter

Publications and source records attributed to G Saeter.

At least 37 records · Page 2Linked to original sources
PubMed1992

High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study.

From 1984 to 1989, 63 patients with diffuse, malignant mesothelioma of the pleura were treated with 4-8 courses of high-dose methotrexate (HDMTX, 3 g total dose) and citrovorum factor rescue. There were 61 male and two female patients of median age 60 years. CT scan was performed before and after treatment and used for response evaluation. Of 60 patients evaluable for response, 37% showed partial or complete remission, 32% showed no change and 32% showed progressive disease. Median survival from start of treatment for all patients was 11 months, for 42 patients with the epithelial type 12 months, and for 20 patients with sarcomatous or mixed types only 5 months. Toxicity was acceptable, with only five patients (8%) terminating therapy due to toxicity. One toxic death occurred. We conclude that HDMTX is an active regimen in malignant pleural mesothelioma. The significantly shorter survival for patients with the sarcomatous or mixed subtypes indicates that further investigations on the activity of HDMTX in mesothelioma should be limited to patients with the epithelial subtype.

Dose-Response Relationship, Drug↗
PubMed1992

The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience.

The study comprised 97 patients treated by the Scandinavian Sarcoma Group for high-grade, extremity-localized osteosarcoma. Chemotherapy was according to the T-10 protocol, with four courses of high-dose methotrexate (HDMTX) given preoperatively at weekly intervals. Seventeen percent of the patients obtained a good (grade III or IV) histologic response, 62% a moderate (grade II) response and 21% a poor (grade I) response. Grade II-IV responders had significantly higher serum MTX levels than grade I responders. Good responders had significantly better survival than moderate/poor responders, and had a trend towards both lower recurrence rate and longer time to recurrence. Five-year overall and relapse-free survival for all patients was 63% and 53%, respectively. Within a group of patients with similar primary tumour response, there was a trend for better survival with increasing serum MTX levels, indicating that individualization of MTX doses according to renal excretion rates may be indicated. The present results underline the importance of introducing effective chemotherapy from the start of osteosarcoma treatment, and that HDMTX alone seems to be insufficient preoperative therapy. The toxicity of HDMTX is generally mild, but we have by cerebral MRI found signal changes in white matter in 14/22 patients; changes that may represent subclinical MTX CNS toxicity. In the subsequent SSG osteosarcoma protocol, cisplatin and doxorubicin has been added to HDMTX from the start of treatment. Our data also suggest that an aggressive approach involving second-line chemotherapy and surgery is indicated for metastatic disease and that such an approach may lead to long-term survival in up to 30% of patients.

Adolescent↗
PubMed1991

Diploid growth pattern of hepatocellular tumours induced by various carcinogenic treatments.

Hepatocellular carcinomas from rats of different strains, subjected to a variety of carcinogenic treatment regimens in different laboratories (initiation by diethylnitrosamine or dimethylhydrazine, promotion by phenobarbital, 2-acetylaminofluorene, nafenopin, orotic acid or deoxycholic acid, growth stimulation by partial hepatectomy or necrogenic CCl4 treatment), were all found to be predominantly diploid by flow cytometric analysis, in contrast to normal liver tissue in which polyploid nuclei were predominant. A switch from polyploidization to diploid growth would thus seem to be a common property of malignant liver tumours. Benign neoplastic liver nodules were likewise predominantly diploid, with the exception of nodules induced by long-term deoxycholic acid treatment in Fischer rats. In addition to containing a majority of polyploid cells, the latter nodules failed to progress to the carcinoma stage.

Animals↗
PubMed1991

Osteogenic sarcoma: MR signal abnormalities of the brain in asymptomatic patients treated with high-dose methotrexate.

The advent of lesions with high signal intensity in periventricular white matter was incidentally observed on T2-weighted images in one patient who underwent magnetic resonance (MR) imaging of the brain after administration of high-dose methotrexate (HDMTX) for osteogenic sarcoma. Twenty-one additional symptom-free patients who had been treated with the same regimen and 10 patients who had undergone cisplatin-based chemotherapy for testicular cancer also underwent examination. Fourteen of the patients with osteosarcoma showed high-signal-intensity lesions in white matter on T2-weighted images. The interval between the last course of chemotherapy and MR imaging was a factor in this finding, as 12 of 14 patients who underwent examination within 2 years after chemotherapy had a positive finding, as opposed to two of eight patients who underwent examination later. The patients with testicular cancer had normal MR images. The occurrence of MR imaging abnormalities in asymptomatic patients treated with HDMTX for osteogenic sarcoma may be subclinical evidence of treatment-related central nervous system toxicity.

Brain↗
PubMed1991

Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study.

From 1982 to 1989, 97 patients with extremity-localized, high-grade osteosarcoma were treated according to the T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (Cancer 49:1221-1230, 1991). Observed histologic response was no certain chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative cisplatin/doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial chemotherapy effect is important for the final outcome in osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for tumor response, suggesting a dose-response relationship for HD MTX treatment.

Adolescent↗
PubMed1990

Liver tumor promoters stimulate growth of transplanted hepatocellular carcinomas.

Cell suspensions or tissue fragments from primary hepatocellular carcinomas and benign neoplastic nodules, induced by treating rats with chemical carcinogens, were transplanted by intraportal injection or subcapsular implantation in the livers of syngeneic host rats. Both nodule and carcinoma transplants produced high numbers of hepatocellular carcinomas in the hosts 2 to 5 mo after transplantation. Treatment of the host rats with liver tumor promoters (phenobarbital or 2-acetylaminofluorene) greatly stimulated tumor outgrowth, demonstrating that even established carcinoma cells can be promoter-sensitive. Tumor outgrowth was also stimulated by partial hepatectomy of the hosts, the regenerative stimulus interacting synergistically with the tumor promoters.

2-Acetylaminofluorene↗
PubMed1990

Management of patients with poor-prognosis nonseminomatous germ cell cancer.

The treatment and outcome of 57 patients with poor-prognosis metastatic nonseminomatous germ cell cancer were reviewed. The patients were treated between 1980 and 1986. Poor-prognosis patients were characterized by the presence of at least one of the following findings: (1) retroperitoneal tumor mass greater than 10 cm; (2) greater than 3 lung metastases, the largest being greater than 2 cm; (3) extrapulmonary, extralymphatic, metastases; and (4) extragonadal primary tumor. The intended treatment consisted of cisplatin-based combination chemotherapy followed by secondary surgery. From 1980 to 1983 a modified Einhorn regimen was used (cisplatin 100 mg/m2 per cycle; CVB). In case of unacceptable vinblastine toxicity, this drug was substituted by VP-16 (500 mg per m2 per cycle; BEP20). From October 1983 the intention was to replace at least 3 of the CVB/BEP20 cycles by BEP60 cycles (days 1-3: cisplatin 60 mg/m2, days 1-3: VP-16 120 mg/m2; days 1, 5, 15: bleomycin 30 mg). There were 33 patients in the CVB/BEP20 group and 24 patients in the BEP60 group. Two patients of the CVB/BEP20 group and 6 patients of the BEP60 group were not evaluable for response, but are included in the survival analysis. The reasons for exclusion from response evaluation were that these patients could not receive the intended chemotherapy in appropriate doses due to severely reduced pretreatment general condition or due to early death. Fourteen patients with multiple lung metastases but no other poor-prognosis criteria had a 93% survival indicating that they did not represent poor-prognosis germ cell cancer. After excluding these 14 patients, the 4-year survival was 58% for 19 CVB/BEP20 patients and 72% for BEP60 patients. This difference did not reach the level of statistical significance in this limited series. The introduction of high-dose cisplatin had thus not led to clearly superior treatment results as compared to CVB/BEP20.

Adolescent↗
PubMed1989

Diploid nature of hepatocellular tumours developing from transplanted preneoplastic liver cells.

Hepatocyte suspensions were transplanted to the livers of syngeneic Wistar Kyoto rats by means of intraportal injection. Labelling of the donor cells with 51Cr or tritiated thymidine showed that 20% of the cells survived the transplantation procedure and were permanently retained by the recipient liver. Hepatocytes transplanted from normal livers produced no tumours, whereas donor cells from preneoplastic livers of rats treated with the carcinogens diethylnitrosamine and 2-acetylaminofluorene produced neoplastic nodules and hepatocellular carcinomas in the recipients. The number of tumours per host liver was proportional to the number of hepatocytes transplanted. Treatment of the host rats with phenobarbitone accelerated tumour development, causing liver cancer in the majority of the animals within three months. As opposed to the polyploid surrounding liver, both phenobarbitone-promoted and unpromoted host tumours contained predominantly (70-90%) diploid cells, regardless of the wide range of transplant ploidies (10-80% diploid cells) achieved by means of centrifugal elutriation. The results indicate that all host tumours arise from diploid donor hepatocytes and that the acquisition of a constitutive, predominantly non-polyploidising growth pattern may be a characteristic property of hepatocellular tumours.

2-Acetylaminofluorene↗
PubMed1989

Neuroendocrine dysdifferentiation and bombesin production in carcinogen-induced hepatocellular rat tumours.

Primary rat hepatocellular tumours, induced by a combination of diethylnitrosamine and 2-acetylaminofluorene, were examined for the presence of neuroendocrine peptides by immunocytochemical methods. Two-thirds of the tumours showed positive immunostaining for either neuron-specific enolase (NSE), protein S-100 or bombesin. NSE was commonly observed both in hepatocarcinomas and in neoplastic nodules, whereas protein S-100 was more frequently seen in carcinomas (49% positive) than in nodules (13% positive). Bombesin, previously shown to function as an autocrine growth factor in small-cell carcinoma of the lung, was present in neurosecretory granules in 13% of the nodules and 29% of the carcinomas. Normal, preneoplastic and peritumorous liver tissue, including the frequent atypical foci present in the latter two categories, was uniformly negative for all neuroendocrine markers. The foci, like the nodules and carcinomas, generally stained positively for the liver tumour marker glutathione S-transferase type P (GSTP). The results suggest that dysdifferentiation of altered hepatocytes in a neuroendocrine direction may be a common, late event in liver carcinogenesis which could possibly contribute to tumour formation, e.g. by establishing autocrine or paracrine circuits.

Animals↗
PubMed1988

Changes in ploidy distributions in human liver carcinogenesis.

Cellular and nuclear DNA content was measured by flow cytometry and the fraction of binucleated cells by fluorescence microscopy in normal adult human livers, hepatocellular carcinomas, cirrhotic 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 binucleated tetraploids containing two diploid nuclei. Thus, polyploidization 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 euploid hepatocellular carcinomas and one investigated case of focal nodular hyperplasia, the percentage of polyploid cells was significantly reduced. Four other carcinomas exhibited a prominent aneuploid (hypotetraploid) peak in addition to the diploid peak. An abnormally low fraction of binucleated cells was also indicated in these tumors. Liver tissue surrounding the tumors had a ploidy distribution similar to that of normal liver. The results suggest that, like in several models of experimental hepatocarcinogenesis, human hepatocellular tumor growth is associated with a decreased polyploidization tendency and a corresponding increase in diploid, divisional growth, which may give the tumors a growth advantage relative to the surrounding liver.

Adolescent↗
PubMed1988

Shift from polyploidizing to nonpolyploidizing growth in carcinogen-treated rat liver.

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.

2-Acetylaminofluorene↗
PubMed1988

2-Acetylaminofluorene promotion of liver carcinogenesis by a non-cytotoxic mechanism.

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 (gamma-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 cytotoxicity (selection of AAF-resistant hepatocytes), since neither AAF alone nor DEN + AAF has any inhibitory effect on overall liver growth.

2-Acetylaminofluorene↗
PubMed1988

The polyploidizing growth pattern of normal rat liver is replaced by divisional, diploid growth in hepatocellular nodules and carcinomas.

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 experimental model.

2-Acetylaminofluorene↗
PubMed1987

Progressive loss of vision in patients with high-grade non-Hodgkin's lymphoma.

Three cases of double-sided neuritis of the optic nerve in patients with lymphomas are described. Two patients with lymphoblastic lymphoma had no other signs of central nervous system (CNS) relapse. All three cases responded to high doses of corticosteroids and/or radiotherapy, suggesting a lymphomatous cause of the papillitis. Optic nerve involvement is reported to be rare in lymphomas, but may become more prominent with aggressive systemic therapy controlling manifestations outside the CNS. Possible causes of optic neuritis in patients with lymphoma are discussed and therapeutic measures are suggested.

Adolescent↗
PubMed1987

Gynaecomastia following cytotoxic therapy for testicular cancer.

Sixteen patients in complete remission after chemotherapy or radiotherapy for testicular cancer developed gynaecomastia which appeared 2 to 9 months after the end of therapy and had a mean duration of 4.8 months. These patients had statistically significant higher levels of oestradiol, FSH and oestradiol/testosterone ratio than a control group without gynaecomastia that had received similar treatment. Both groups tended to have testosterone levels in the lower normal range and all patients had normal levels of beta-HCG, prolactin and progesterone. The gynaecomastia in our patients was probably the result of an absolute increase in oestradiol or an increase relative to testosterone. Cytotoxic therapy affects both spermatogenesis and Leydig cell function, with a resultant rise in gonadotrophins which may in turn increase testicular oestrogen secretion. In testicular cancer patients, gynaecomastia may be a sign of tumour activity but it may also be caused by hormonal changes resulting from cytotoxic therapy. It is our experience that the latter treatment-related type is harmless, transient and unrelated to the patient's prognosis.

Adolescent↗
PubMed1987

Transplantation of preneoplastic rat hepatocytes by intraportal injection.

Hepatocyte suspensions prepared from inbred male Wistar-Kyoto rats were transplanted to the livers of syngeneic recipients by injection into the portal venous system immediately after partial hepatectomy. Donor cells were labelled with 51Cr in vitro before transplantation. Animals were sacrificed 1 hr, 10 hr, 48 hr, or 1 week later and the liver radioactivity was measured in a gamma counter. Total liver radioactivity declined rapidly during the first 10 hr after transplantation, and then stabilized. After 1 week, 15-20% of the injected radioactivity still remained, indicating that this fraction of the injected cells was retained by the liver. The percentage was unaffected by the number of cells injected. In another experiment, 10(6) hepatocytes from a carcinogen-treated rat were transplanted to syngeneic rats fed 0.05% phenobarbital in the diet. Recipients developed liver carcinomas from 7 weeks after transplantation, and at 5 months 4 out of 5 animals showed severe debility and had large hepatocellular carcinomas. This model generates tumors considerably faster than those previously described, and is well suited for the study of the tumorigenic potential of subclasses of cells in liver carcinogenesis.

Animals↗
PubMed1986

Fifty-five patient years' experience with a totally implanted system for intravenous chemotherapy.

A subcutaneously implanted injection system represents a new method of central venous access. Seventy-eight injection capsules were implanted in 75 cancer patients undergoing intermittent chemotherapy. The actuarial median functional survival of the injection capsules was 16 months, and with a cumulative function time of 55 patient years the complication rate was only one complication every 990 days. No cases of septicemia and few cases of local infection or clotting of the system were seen. Patient activities were not restricted, and maintenance of the system between treatment courses was unnecessary. However, in 9% of the implants a tendency to erosion through the skin was observed, necessitating explantation or reimplantation. Injection capsules seem to be particularly suited for intermittent chemotherapy, including short-term infusions and blood sampling.

Adolescent↗