Markus Fopp - Academia.edu (original) (raw)

Papers by Markus Fopp

Blood, 1998

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acut... more High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% ve...

British journal of …, 1994

Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphobl... more Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11-69 months (median 21 months). The disease-free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of +/- 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.

Acta Haematologica, 1976

Granulocytes were harvested from hematologically normal individuals using continuous flow centrif... more Granulocytes were harvested from hematologically normal individuals using continuous flow centrifugation (CFC) or filtration leukapheresis (FL). The isolated granulocytes were labeled in vitro by 3H-diisopropyl fluorophosphate (3H-DFP) and autotransfused. Their intravascular fate was analyzed by autoradiography. Immediately after autotransfusion the majority of granulocytes administered, collected in the marginal granulocyte pool. Margination was particularly prominent in granulocytes isolated by FL. The distribution of transfused granulocytes between the circulating and the marginal granulocyte pool showed wide and irregular fluctuations in time. Margination of transfused granulocytes was counterbalanced, and its fluctuation between the two intravascular pools was stabilized by prednisone treatment. The transit of transfused granulocytes from blood to tissue seemed to be governed by a random process, the half-disappearance time being either normal or prolonged. Compatible granulocytes administered to hematologically normal recipients circulated for at least 20 h.

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum

family (H-, K-, and N-ras) acquire their transforming potential mainly through distinct point mut... more family (H-, K-, and N-ras) acquire their transforming potential mainly through distinct point mutations leading to alterations in structure and function of the 21 kd ras gene product.&amp;#39;2 These activating mutations are found in a wide variety of tumors. In hematobogic disorders, ras activation is predominantly found in N-ras.39 Our results (unpublished observations)9 show, in agreement with others,7 an N-ras

British journal of cancer, 1978

Blood lymphocytes from 47 patients with lung carcinoma have been tested for cytotoxicity against ... more Blood lymphocytes from 47 patients with lung carcinoma have been tested for cytotoxicity against cells isolated from the autologous tumour. Significant cytotoxic potential was found in 15 cases. The effectors were also tested against allogeneic tumour targets from lung and other sites. Reactions were only rarely detected (2/32 positive against lung and 1/13 positive against non-lung cells). The restriction of cytotoxicity to the autologous combination was also apparent in in vitro-generated effectors. Blood lymphocytes were co-cultivated with autologous tumour and subsequently tested against autologous or allogeneic targets. Cytotoxicity was found in 13/17 lung tumours against autologous tumour, with no reactions recorded against allogeneic tumour targets, but one case positive against the K562 cell line. These data suggest either the expression of individually distinct antigens on human pulmonary neoplasms, or the requirement for histocompatibility between target and effector in cy...

Blood, 1988

We have conducted a follow-up study of a patient with myelomonocytic leukemia exhibiting an N-ras... more We have conducted a follow-up study of a patient with myelomonocytic leukemia exhibiting an N-ras mutation (Gln61----Lys61) using the polymerase chain reaction method and synthetic oligonucleotide hybridization probes. This method allowed us to detect as little as 3% of N-ras-mutated cells within a population. When the patient went into clinical remission, the mutation became undetectable. When a relapse occurred, the blasts did not carry the N-ras mutation. Analysis of M13 cloned amplified N-ras sequences from relapse DNA revealed exclusively the wild type allele of the N-ras gene. These findings suggest that the relapse cell population is derived from a different clone than the acute phase population. Furthermore, the data argue that N-ras mutation is not an initiating lesion in this case of acute myelomonocytic leukemia (AMML).

European Journal of Cancer and Clinical Oncology, 1987

Antiviral Mechanisms in the Control of Neoplasia, 1979

Journal of Medical Virology, 1997

A nested polymerase chain reaction assay (nPCR) was used to investigate the potential of human pa... more A nested polymerase chain reaction assay (nPCR) was used to investigate the potential of human parvovirus B19 DNA to persist in blood or bone marrow samples obtained either from blood donors or cadaveric bone donors or from patients presenting with clinical signs of parvovirus B19 infection. The presence of parvovirus B19 specific antibody in blood was tested by enzyme immunoassay (EIA). B19 virus genome was not detected in any blood sample of 115 blood donors, of whom 92 (80%) had anti-B19 IgG antibody only as an indication of past infection. In contrast; B19 virus DNA was detected in the bone marrow of 4 out of 45 bone donors. Each one of the serum samples available for 3 of these 4 individuals contained anti-B19 IgG antibody. Among 84 patients with clinical manifestations of parvovirus B19 infection, 17 (20%) had B19 virus DNA in bone marrow. Eight of the latter patients had anti-B19 IgG antibody in their blood but neither anti-B19 IgG nor B19 virus DNA. These data document the ability of parvovirus B19 DNA to persist in the bone marrow of asymptomatic individuals and patients with parvovirus B19 infection suspected on clinical grounds.

Investigational New Drugs, 1985

Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin... more Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin. Dosages were escalated from 7 mg/m2/d to 15 mg/m2/d for 3 consecutive days. One patient achieved a partial remission and antitumor activity was seen in most other patients. Stomatitis was dose-limiting at 15 mg/m 2. Phase II trials are warranted and we propose a schedule of 12 mg/m2/d for 3 consecutive days.

International Journal of Cancer, 1978

Blood lymphocytes from 22 cancer patients were examined for cytotoxicity against autologous tumou... more Blood lymphocytes from 22 cancer patients were examined for cytotoxicity against autologous tumour cells in a short-term %r release assay. Only three showed reactivity. In an attempt t o increase cytotoxic potential in these and Induce reactivity in non-reactive cases, the lymphocytes were cultured alone or with autologous tumour cells for 6 days, Upon subsequent testing against frozen, stored targets, nine samples reacted, including two of those with primary reactivity. In seven cases augmented cytotoxicity was evident in mixed cultures compared with lymphocytes cultured alone. Two of 10 cases showed cytotoxicity against the K562 cell line after culture and, in two of 13 tests in which allogeneic tumour biopsy targets were used, weak reactivity was bound. Cytotoxiclty for autologous tumour biopsy cells was uniformly accompanied by positive blastogenesis in MLTl assays. In four cases blastopenesis occurred without the induction of cytotoxiclty.

International Journal of Cancer, 1988

DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukem... more DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT + GAT transitions in codon I2 and one CAA + AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a followup study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N-ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N-ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.

European Journal of Haematology, 2009

Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myel... more Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myeloid leukaemia (AML) from a Swiss Phase III multicentre study (SAKK 30/85), we measured the m-RNA expression of the genes from the multidrug resistance gene 1 (MDR1), the multidrug resistance associated protein (MRP), glutathione-S-transferase (GST) pi, bcl-2 and topoisomerase (topo) IIalpha. P-glycoprotein (p-gp) was measured by Western blot, and GST activity by functional assays. To analyse progression-free (PFS) and overall survival (OS), parameters were prospectively divided into &amp;quot;low&amp;quot; and &amp;quot;high&amp;quot; groups, according to their median values (exceptions: MDR1 and p-gp). Median follow-up was 60 months. MDR1- and MRP mRNA levels correlated with each other (r=0.54, Spearman), FABM4/M5 and extramedullary disease. &amp;quot;Low&amp;quot; bcl-2-mRNA predicted longer PFS: 22 months vs. 7 months (median,p=0.02, log rank), and longer OS: 64 months vs. 14 months (p=0.06). &amp;quot;Low&amp;quot; topo IIalpha predicted poorer outcome: median PFS 9 vs. 19 months (p=0.03); median survival 12 months vs. &amp;quot;not reached&amp;quot; (p=0.03). An improved outcome tendency, albeit nonsignificant, was seen in p-gp-negative patients. In a Cox model adjusted for age, performance status, presence of Auer rods, FAB type and clinical response, bcl-2 and topo IIalpha mRNA levels retained their predictive values.

$Research paper thumbnail of Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma$

Cancer Immunology, Immunotherapy, 2006

Background: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor anti... more Background: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer. Patients and methods: Autologous DC of HLA-A*0201 + patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA 14-22), prostatic acid phosphatase (PAP 299-307), prostate-specific membrane antigen (PSMA 4-12), and prostate-specific antigen (PSA 154-163). DC were intradermally applied six times at biweekly intervals followed-in the case of an enhanced immune response-by monthly booster injections. Immune monitoring during the time of ongoing vaccinations (12-59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in vitro cytotoxicity assays. Results: Of the initial six patients, three qualified for long-term multi-epitope DC vaccination. This regime was tolerated well by all three patients. The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time. Conclusions: DC-based multi-epitope immunotherapy with repeated boosting in men with hormonerefractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.

British Journal of Haematology, 1985

The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (A... more The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS-D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15-100%): the MS2 group of 14 cases with 10-70% NCAE positive cells (SB: 65-100%) and the MS3 group of 11 cases with 70-100% NCAE positive cells (SB: 89-100%). Ia expression was determined by complement-dependent cytotoxicity, immunofluorescence and immunoperoxidase methods. A similar high percentage (80%) of patients from both group MS1 and MS2 expressed Ia on the surface of 32-100% of the cells. Furthermore, individual comparison of all cases from these two groups showed no correlation between Ia, NCAE and SB expression. Only in the 11 cases from the MS3 group, which included nine cases of promyelocytic leukaemias, was there a correlation between very low expression of Ia antigen with the high NCAE expression. Thus, for AML with a low degree of differentiation the expression of Ia seems to be independent of conventional cytochemical markers of cell maturation.

Annals of Hematology, 1997

MTS1, a tumor suppressor gene located on chromosome 9p21, has been shown to be altered in a numbe... more MTS1, a tumor suppressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol. No deletion of the MTS1 gene was found in any of the AML samples tested. There was no significant association between expression of MTS1 and response to therapy, progression-free, or overall survival. Except for a negative correlation between MTS1 level and leukocyte count at diagnosis (p = 0.03), there was also no association with any of the known prognostic parameters in AML. We conclude that MTS1 shows a significantly higher expression in leukemic than in normal peripheral blood cells, that deletion of MTS1 is not a frequent event in AML, and that its expression is not significantly correlated with outcome of the disease.

Annals of Hematology, 1993

Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has bee... more Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia. All patients were treated during a 5-year period in 12 hospitals on a common protocol of the Swiss Study Group for Clinical Cancer Research (SAKK). Protocol 30/85 comprises a double induction and one course of consolidation. Of 206 registered patients, 199 were evaluable; 118 of 199 (59%) patients entered completed all three cycles of chemotherapy. These 118 patients received a median (range) of 18 (3-44) units of red blood cells and 12 (2-61) platelet transfusions during 112 (70-129

Leukemia, 1999

Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and... more Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (␤: 0.68, s.e.: 0.28, P = 0.015) and overall survival (␤: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.