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G Saeter

Publications and source records attributed to G Saeter.

70 records · Page 4Linked to original sources
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↗
PubMed1986

Changes in cellular ploidy and autophagic responsiveness during rat liver carcinogenesis.

Liver carcinogenesis was initiated in young rats by diethylnitrosamine/partial hepatectomy and promoted by dietary 2-acetylaminofluorene (for 4 weeks). Eight weeks after initiation, hepatocytes were isolated by means of collagenase perfusion and analyzed by means of flow cytometry. Whereas cells and cell nuclei from normal or hepatectomized livers were predominantly tetraploid, most of the hepatocytes/nuclei from carcinogen-treated rats were diploid. Neoplastic liver nodules and hepatocellular carcinomas also contained almost exclusively diploid nuclei, suggesting that diploidization may be an essential feature of liver carcinogenesis. Two-parametric analysis (simultaneous flow cytometric determination of DNA and protein content within the same cell) revealed that the diploid cells were only half as big as the tetraploid cells. They could therefore be separated from the latter by centrifugal elutriation. Normal, isolated hepatocytes responded to amino acid deprivation by increasing their rates of autophagic sequestration (measured with electroinjected (14C)sucrose as a probe) and endogenous protein degradation, the resulting protein loss eventually leading to cell death. Hepatocytes from carcinogen-treated rats were much less responsive to amino acid deprivation, preserved their protein better, and survived for longer periods of time in culture than did normal cells. The reduced autophagic responsiveness may conceivably give carcinogen-altered cells a survival advantage even in vivo, that could contribute to their outgrowth during carcinogenesis.

2-Acetylaminofluorene↗
PubMed1984

Carcinoma of the prostate with soft tissue or non-regional lymphatic metastases at the time of diagnosis: a review of 47 cases.

The clinical course of 47 patients with carcinoma of the prostate who at the time of initial presentation had metastases to soft tissue or non-regional lymph nodes was retrospectively reviewed. The response rate to primary hormonal treatment (orchiectomy or oestrogens) and the duration of response were similar to those of 47 other patients presenting with skeletal metastases only. The survival of the patients in the study group was not statistically different from that of patients with skeletal metastases only. The results suggest that patients presenting initially with metastases to non-regional lymph nodes or soft tissue should be treated by the same therapeutic methods as for disseminated prostatic cancer in general (oestrogens or orchiectomy). Slight or no urinary symptoms at the time of initial presentation in spite of a locally advanced tumour was a common finding; 20% of the patients had normal serum prostatic acid phosphatase despite the presence of disseminated disease. Lymph node enlargement in the left supraclavicular fossa was the most common site of non-regional lymphatic spread. Elderly males with metastatic carcinoma in this region should be investigated for the possibility of prostatic cancer.

Adult↗
PubMedDate not supplied

Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide.

We report on the clinical course and outcome of 28 patients, treated at The Istituti Ortopedici Rizzoli between 1995 and 1997 for osteosarcoma of the extremities metastatic to the lung at presentation. The treatment for these patients was the following: primary chemotherapy with cisplatin, adriamycin and high dose of methotrexate and ifosfamide followed by simultaneous resection of primary and metastatic lesions (when feasible), and further chemotherapy. After primary chemotherapy, lung metastases disappeared in 6 patients, whereas metastases in 3 remained surgically unresectable. These 9 patients received surgical treatment of the primary tumor only. In the remaining 19 patients, after chemotherapy, a simultaneous resection of the primary and metastatic tumor was performed. The resection of metastatic lesions was complete in 18 cases and incomplete in one. Three of the 4 patients who did not achieve a tumor-free status died in a few months and one is still alive with uncontrolled disease. With a median follow-up of 32 months (19-43) of the 24 patients who achieved remission, 12 (55%) remained continuously free of disease, 11 relapsed with new metastases and 1 died of chemotherapy-related toxicity. The 2-year DFS and OS were 36% and 53% respectively. These results are much worse than those achieved in 114 contemporary patients with localised disease (2-year DFS: 81%) treated in the same period and they are superimposible to the results achieved in 23 patients previously treated with the same protocol, but with standard dose of ifosfamide (2-year DFS: 32%). However, it must be underlined that, as regards prognosis, patients with metastatic disease at presentation are a hetero-geneous group. The DFS was significantly higher for patients with only one or two metastatic lesions than for patients with 3 or more lesions (2 year DFS: 78% vs. 28%). In 12 of the 19 patients who had a complete simultaneous resection of the primary and metastatic tumor, a strong correlation between the degree of necrosis of the primary and metastatic lesions was found. We conclude that in patients with osteosarcoma of the extremity with lung metastases at presentation: a) the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic tumors works very well only for those patients who present with one or two metastatic nodules whereas for patients with 3 or more pulmonary metastases the prognosis is very poor; b) within the 4-drug regimen used in this study, the increment of ifosfamide dose from 10 g/m2 to 15 g/m2 for cycle does not improve prognosis; c) the strong correlation found between the histologic response of the primary tumor and metastases supports the strategy, largely used nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemo-therapy on the basis of the primary tumor histologic response to preoperative chemotherapy.

Adolescent↗
PubMedDate not supplied

Intracranial primary leiomyosarcoma arising in a teratoma of the pineal area.

The case of a 33-year-old man with a primary leiomyosarcoma arising in a mature teratoma in the pineal area is presented. The tumor extended into the posterior part of the third ventricle and caused hydrocephalus. Its smooth muscle derivation was confirmed by immunohistochemistry and electron microscopy. The patient has been followed for more than 2 years after surgery and postoperative radiotherapy. He has full working capacity and there are no signs of tumor recurrence. To our knowledge this is the first presentation of a leiomyosarcoma derived from a teratoma in the pineal area.

Adult↗