Search PubMed⌕ Search

Biomedical subjects

S Seeber

Publications and source records attributed to S Seeber.

At least 181 records · Page 10Linked to original sources
PubMed1993

Prognosis and treatment of disseminated uveal melanoma.

BACKGROUND: The clinical course of uveal melanoma differs greatly from that of cutaneous melanoma. METHODS: Twenty-four patients with metastatic uveal melanoma (13 men and 11 women; median age at diagnosis, 56 years [range, 17-67 years]) were evaluated retrospectively. RESULTS: Main sites of metastases were liver (87%), lung (46%), bone (29%), and skin (17%). Median relapse-free survival time was 36 months (range, 5-240 months). Median survival time after clinical detection of metastases was 9 months (range, 1-54 months). Relapse-free survival time was significantly greater in patients 50 years of age or younger. After manifestation of metastases, the clinical course was more favorable in patients in whom the liver was either not involved at all or not among the first sites of dissemination. These patients had a median survival time of 19 months, compared with 7 months for patients in whom the liver was involved initially. First-line systemic treatment of metastatic disease yielded three cases of stable disease lasting 6-14 months, but no complete or partial response. Three patients received intraarterial liver perfusion as first- or second-line treatment, resulting in one partial response, which lasted 6 months. CONCLUSION: Treatment and prognosis results of patients with metastatic uveal melanoma were poor, especially when the disseminated to the liver; survival time of approximately 9 months can be expected.

Adolescent↗
PubMed1993

Analysis of the p53 gene in patients with isochromosome 17q and Ph1-positive or -negative myeloid leukemia.

Increased incidence of p53 gene aberrations or chromosome 17p monosomy resulting from an isochromosome 17q [i(17q)] has been observed with transition of chronic myelogenous leukemia (CML) to myeloid blast crisis (BC), and in some patients with poor risk acute myeloid leukemia (AML) progressing from myelodysplastic syndrome (MDS). These data suggested that disease progression may be linked to bi-allelic inactivation of p53. Here, we report on p53 gene analyses of nine patients with CML-BC and AML who showed an i(17q) as characteristic cytogenetic anomaly. Using Southern blots, agarose gel electrophoresis and single-strand conformation polymorphism analyses of PCR products from genomic DNA and cDNA, spanning exons 4 through 9, we did not detect any structural abnormalities of the remaining p53 allele. These findings question the hypothesis that p53 gene alterations are the principal molecular event responsible for progression of CML chronic phase or MDS to i(17q)-positive CML-BC or AML, respectively.

Adult↗
PubMed1993

The neu-oncogene product in serum and tissue of patients with breast carcinoma.

BACKGROUND: A soluble 105 kD neu-related protein is detectable in conditioned medium from breast cancer cells expressing the neu-oncogene product and in serum of nude mice bearing tumors that overexpress neu-oncogene. PATIENTS AND METHODS: In 100 patients with primary (n = 33) relapse-free (n = 6) and metastatic (n = 61) breast carcinoma the serum levels of the soluble neu-related protein were investigated by ELISA techniques. Median age was 57 years, range 26-89 years. RESULTS: The neu-protein serum levels were below 40 HNU/ml (human neu-antigen unit) in 72 patients and 40 or more HNU/ml in 28 patients. In 30 patients with primary breast carcinoma, tested before mastectomy, all serum-neu-protein samples were negative. However, 26 of 61 metastasized patients (43%) were serum-neu-protein-positivity. In disseminated disease (n = 61), serum-neu-protein-positivity was more likely to be seen in patients with visceral metastases (18/33 = 54%), than in patients with nonvisceral metastases (8/28 = 28%). Furthermore, monitoring of the serum-neu-protein levels reflected clinical course. For 53 patients original paraffin-embedded tumor material was available for studying immunohistochemical neu-protein expression. In 39/53 (73%) patients immunohistochemical and ELISA data showed corresponding results. In 27/30 (90%) patients, from whom sera and tissue could be obtained at the same time at primary mastectomy, results of immunohistochemistry in primary tumor and serum ELISA were negative and mutually confirmatory. However, the other three patients were positive for immunohistochemical neu-protein expression in primary tumor but negative for serum-neu-protein expression. CONCLUSIONS: Our results suggest that patients with advanced breast cancer and an elevated serum-neu-protein level may have a poor clinical outcome. This test might be a useful tool for monitoring patients with advanced breast carcinoma, but not those with early disease. Further prospective studies are warranted to elucidate the question of whether this test can contribute to determining prognosis and treatment strategies.

Adult↗
PubMed1993

Impact of interferon alpha-induced cytogenetic improvement on survival in chronic myelogenous leukaemia.

The objective of this study was to investigate the prognostic impact of the reduction of Philadelphia chromosome (Ph) positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha. Therefore, we evaluated the outcome of patients with previously untreated chronic phase Ph-positive CML, enrolled from 1984 to 1990 into two consecutive IFN trials at our institution. Of a total of 71 patients, 62 (87%) were evaluable for cytogenetic response. No cytogenetic improvement was seen in 16 patients (23%), 28 patients (38%) had a decrease in Ph-positive bone marrow metaphases to levels ranging from 35% to 95%, and nine patients (13%) to levels between 5% and 34%. In nine patients (13%), Ph-positive metaphases were no longer detectable. After a median follow-up period of 33 months, the projected 5-year survival is 55% for the 62 patients evaluable for cytogenetic response. In this patient population there was no significant difference in the survival probability according to patients' risk status as defined by the Sokal score. Categorization according to the extent of Ph reduction, however, allowed three groups with significantly different prognoses to be identified. Patients achieving a Ph reduction to less than 35% were found to constitute a low risk group with a median survival not yet known and a projected 5-year survival of 90%. The 5-year survival rate was 55% for patients with a Ph reduction to levels between 35% and 95%, and less than 10% for those without any cytogenetic improvement. Thus, this study demonstrates that cytogenetic improvement on IFN treatment is an important prognostic factor for survival.

Adolescent↗
PubMed1993

[Delayed retroperitoneal lymph node excision in treatment of advanced non-seminomatous germinal cell tumors. I. Intraoperative findings in marker converted tumor].

Retroperitoneal lymphadenectomy was performed in 462 patients with testicular cancer. A total of 142 patients with advanced non-seminomatous germ cell tumours underwent retroperitoneal lymphadenectomy following cisplatin-based polychemotherapy. After inductive chemotherapy all of the patients described (108/142) showed seroconversion of tumour markers. Histology following RLA revealed vital tumour in 41% and teratoma in 12%. It was not possible to distinguish preoperatively between non-malignant residual tissue and vital tumour. In addition, sonography, computed tomography, and the tumour marker results did not correlate significantly with the intraoperative histopathological findings. Although histopathological confirmed complete remission was achieved in 47% of the patients with chemotherapy alone, subsequent retroperitoneal lymphadenectomy remains mandatory in cases with residual retroperitoneal lesions and pathological partial remission.

Adult↗
PubMed1993

Ifosfamide in the treatment of soft-tissue sarcomas: experience at the West German Tumor Center, Essen.

The response of ifosfamide-based chemotherapeutic regimens was retrospectively analyzed in adult patients with advanced soft-tissue sarcoma who were treated at the West German Tumor Center, Essen, between 1978 and 1990. Single-agent ifosfamide was given either in split doses of 60-80 mg/kg by 4-h infusion over 5 days or as a continuous 24-h infusion of 5 g/m2. Ifosfamide was given either in split doses of 40-50 mg/kg over 5 days or as a continuous infusion of 5 g/m2 in combination with doxorubicin (40-60 mg/m2, day 1), cisplatin (20 mg/m2, days 1-5), or etoposide (100 mg/m2, days 1, 3, and 5). Mesna was given to all patients as prophylaxis against urotoxicity. Of 54 evaluable patients receiving single-agent ifosfamide, 5 achieved a complete response (CR) and 10 showed a partial response (PR), for an overall response rate of 28%. Objective responses were more frequent in previously untreated patients (47%) than in pretreated patients (15%; P < 0.01). The addition of doxorubicin (n = 41) or cisplatin (n = 29) to ifosfamide did not significantly increase the response rate (29% and 41%, respectively) or median duration of remission as compared with ifosfamide alone. In addition, no significant difference was observed between the two ifosfamide regimens used: the 24-h continuous-infusion schedule (5 g/m2 per course, 27% response rate) and the 5-day fractionated regimen (10-15 g/m2 per course, 19% response rate). We conclude that the response and the median duration of remission produced by single-agent ifosfamide compare favorably with the results achieved using single-agent doxorubicin and the usually more toxic combination regimens.

Adolescent↗
PubMed1993

[The clinical picture and therapy of aggressive fibromatosis (desmoids)].

Desmoid tumors are accounted among histologically benign soft tissue tumors. Though metastases do not occur the clinical course of the disease with their tendency to grow locally aggressive and to relapse after curative intended surgery is similar to sarcomas. After surgical excision adjuvant therapy of desmoid tumors is necessary in such cases, where a radical excision with a wide margin is not possible, or must be doubted or after the surgical excision of a locally recurrent tumor. Radiation doses of 50 to 60 Gy reduce the risk of local recurrence of desmoid tumors to 18%. In such cases, where surgery and radiotherapy have been leading to incomplete responses, systemic therapy with hormones (tamoxifen or progesterone), with alkylating agents (e. g. ifosfamide) or with prostaglandin antagonists (indomethacin) is possible. The published data on therapeutic responses to the treatment of desmoid tumors are scarce. We are reporting on seven of our own cases, treated with surgery and radiotherapy (four) or with a combination of surgery, radiotherapy, hormones and chemotherapy (three).

Adult↗
PubMed1993

[Current developments in chemotherapy of advanced testicular tumors].

The chemotherapy of disseminated testicular cancer is subject to continuous change and further improvement. Because of the high efficacy, with a curability over 90% for patients with good prognostic criteria, ongoing trials investigate how far the toxicity can be reduced without a negative impact on the cure rate. Besides the standard protocols for good risk (PEB x 3; PE x 4) the substitution of cisplatinum by carboplatinum (CEB) or bleomycin by vinblastine (VPV;CEV) is currently being tested in prospective randomized trials. In patients with poor prognostic criteria, e.g. advanced disease according to the Indiana classification, the cure rate is only 50-60% with standard PEB x 4. The substitution of bleomycin by ifosfamide (PEI) seems to improve this result significantly, whereas dose escalation of platinum to double dose alone is not effective. A major advance can be expected from the early introduction of very high dose chemotherapy, within the first weeks of induction chemotherapy either by administration of megadose chemotherapy as a single cycle or by administration of sequential intermediate-dose cycles, using haematopoietic growth factors and peripheral blood progenitor cells. These types of dose-intensive regimens will be compared with standard PEB or PEI in prospective randomized trials in poor risk nonseminomatous germ cell tumours in first-line treatment as well as for salvage chemotherapy. For seminoma, however, due to the high platinum sensitivity the possibility of a carboplatinum single-agent chemotherapy for good risk seminoma patients is currently being investigated in prospective trials. The development of these new treatment strategies needs even more intense cooperation and joint effort from specialists in urology, surgery, radiotherapy, haematology, and medical oncology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Clonogenic assay is not predictive but reflects therapeutic efficacy of interferons in the treatment of chronic myelogenous leukemia.

Patients with chronic myelogenous leukemia (CML) have been treated with interferon (IFN) alpha-2b alone or in combination with IFN gamma. In order to predict clinical response to IFN, bone marrow samples from 15 CML patients were incubated with serial dilutions of IFN alpha-2b to obtain the IC50 values for erythroid burst forming units (BFU-E) and granulocyte-macrophage colony forming units (CFU-GM). A dose-dependent inhibition of at least one lineage was observed in all but one sample. An inhibitory effect of greater than 50% was reached for BFU-E in 8/14 patients and for CFU-GM in 10/14 patients. All three patients with no response (NR) to IFN treatment had IFN-sensitive BFU-E and CFU-GM. In four patients with hematologic remission (HR) or partial hematologic remission (PHR), BFU-E or CFU-GM were affected very little by the inhibitory effect of IFN. These observations suggest no predictive value for pretesting IFN sensitivity in vitro. The in vivo effect of IFN on the hemopoietic progenitor cells BFU-E and CFU-GM was evaluated in patients treated with either IFN alpha-2b alone (n = 11), or in combination with low dose IFN gamma (n = 10). All patients were newly diagnosed and not pretreated. After a median treatment duration of 11 months (range 3-25) a significant decrease in BFU-E and CFU-GM was observed in both groups of patients. We conclude that in vitro colony growth reflects the therapeutic efficacy of IFN.

Adult↗
PubMed1992

Relation between leukocyte counts and cortisol secretion in CML patients undergoing combined TNF alpha/IFN alpha therapy.

During long-term interferon alpha-2b (IFN) therapy of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients, short-term effects of tumor necrosis factor alpha (TNF) on peripheral leukocyte counts, as well as cortisol and corticotropin (ACTH) release were studied. TNF (40-160 micrograms/m2) was given as a 2-h infusion on 5 consecutive days every 3 weeks, in addition to s.c. daily IFN injections (4 mio U/m2), to four (two male/two female) patients, who had been treated for more than 8 months with IFN and additionally for 0-7 months with TNF. Leukocyte counts, cortisol, and ACTH were determined at 30-min intervals between 4 p.m. and midnight. Profiles were determined the day before and on day 1 of TNF therapy. Leukocyte numbers decreased 30 min after start of TNF administration and increased 30-60 min later with a rebound until the next TNF application. The increase of leukocyte counts was due mostly to neutrophil granulocytes. ACTH levels increased 30 min, cortisol 60 min, and leukocyte counts 90 min after start of TNF infusion. Metopirone, an inhibitor of cortisol synthesis given to one patient, suppressed the TNF-induced stimulation of cortisol secretion and subsequent increase of leukocyte counts, while ACTH blood levels were enhanced. It was concluded that leukocyte count increases after TNF/IFN administration might be related to TNF-evoked cortisol secretion.

Adrenocorticotropic Hormone↗
PubMed1992

Cytotoxicity of adriamycin, idarubicin, and vincristine in acute myeloid leukemia: chemosensitization by verapamil in relation to P-glycoprotein expression.

A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in blasts isolated from 37 patients with newly diagnosed and pretreated acute myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was studied in relation to the expression of the membrane efflux pump P-glycoprotein (PGP) as determined by a semiquantitative flow-cytometric proceder. A slight positive correlation was found between the fraction of cells expressing PGP and the ID50 values for ADM and VCR, but not between cellular PGP content and sensitivity to IDA. The overall data showed no significant sensitization effect of VRP. However, in specimens with more than 10% cells expressing PGP, 2 microM VRP sensitized cells to ADM and VCR significantly. The median of sensitization ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the cytotoxicity of IDA was observed. Related to the clinical status, the median fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n = 16) in comparison to patients with de novo AML (n = 19). No differences in ID50 values were observed between newly diagnosed and pretreated patients. However, SRs for ADM and VCR were higher in samples of pretreated patients compared with de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in leukemic blasts by application of chemosensitizers or, potentially, alternative anthracyclines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Tumor necrosis factor alpha modifies resistance to interferon alpha in vivo: first clinical data.

Patients with Philadelphia-positive chronic-phase chronic myelogenous leukemia (CML) resistant to interferon (IFN) alpha were treated in a phase I/II study with recombinant human tumor necrosis factor alpha to overcome IFN alpha resistance. Doses of 40, 80, 120 or 160 micrograms/m2 TNF alpha were given as 2-h infusions on 5 consecutive days every 3 weeks. IFN alpha (4 x 10(6) IU/m2 s.c., daily) treatment was continued. Six patients were treated, completing 1-24 (median, 12) treatment cycles. Five of the six patients achieved partial hematological remission, while the remaining patient had to stop treatment because of WHO grade 4 thrombocytopenia following the first TNF alpha cycle. No complete hematologic remission or cytogenetic improvement was seen. Side-effects were similar to those described for both substances alone. Maximum tolerable TNF doses usually varied between 80 micrograms/m2 and 160 micrograms/m2. To examine possible pathways of TNF activity in these patients, interferon receptor status and (2'-5')-oligoadenylate synthetase levels were examined in peripheral blood mononuclear cells. Both parameters remained unchanged during TNF alpha treatment. These preliminary data point to significant clinical efficacy of additionally applied TNF alpha in IFN alpha-resistant CML patients.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders.

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low-dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied. Elevated ANA titers were found in 5/19 (26%) of CML patients at the time of diagnosis and in 3/18 (17%) of patients treated with hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of autoimmune disease appeared. All these patients were under long-term IFN treatment and were in remission of disease. In three patients criteria for systemic lupus erythematosus were fulfilled. Severity of side effects had led to the discontinuation of IFN treatment in these patients. The data indicate that IFN-alpha and IFN-gamma can induce ANA associated with autoimmune disease in patients with myeloproliferative disorders.

Adult↗
PubMed1992

No correlation between site of breakpoint in the BCR gene and platelet counts in Philadelphia chromosome-positive CML.

In chronic myelogenous leukemia (CML) malignant cells are characterised by the Philadelphia chromosome (Ph), resulting from a translocation t(9;22). The position of the breakpoint within the major breakpoint cluster region (M-bcr) on chromosome 22 has been shown to correlate with the clinical course of the disease or, more recently, thrombopoietic activity. We have therefore determined the breakpoint localisation in 53 Ph-positive CML patients. Following the 5'/3'-region definition of Inokuchi et al. Leukemia Research 15, 1067 (1991) [1], 22 of our patients have 5' and 31 of our patients have 3' orientated breaks. No correlation was found between platelet counts and breakpoint localisation.

Chromosome Aberrations↗
PubMed1992

Opposite sensitivity to the antiproliferative action of interferon-alpha and granulocyte-macrophage colony-stimulating factor in monoblastic U937 cells.

Three variants of the human monoblastic cell line U937 with different degrees of sensitivity to the antiproliferative action of interferon-alpha (IFN-alpha were examined for phenotypic differences. The highly IFN-sensitive variant U937-V expressed twice as many IFN-alpha binding sites as both its IFN-alpha-resistant derivative U937-VR and the cell line U937 exhibiting a 20-fold reduction in IFN-alpha sensitivity as compared to U937-V cells. All three variants were IFN-reactive with regard to induction of 2',5'-oligoadenylate (2-5A) synthetase activity and were similarly sensitive to the growth-inhibiting action of IFN-gamma and tumor necrosis factor. Responsiveness to the antiproliferative effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), however, was confined to cell lines U937 and U937-VR. Although expressing a comparable number of GM-CSF receptors, the highly IFN-sensitive variant U937-V was refractory to GM-CSF. Flow cytometry revealed a marked difference in the expression of the antigen CD11b which was detectable on 85% of cells of the U937-V line but only on approximately 25% of cells derived from the U937 and U937-VR lines. Results thus demonstrate opposite sensitivity of U937 cells to the growth-inhibiting action of IFN-alpha and GM-CSF, apparently dependent on the state of U937 differentiation as determined by expression of the CD11b antigen.

2',5'-Oligoadenylate Synthetase↗