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Biomedical subjects

G Gastl

Publications and source records attributed to G Gastl.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Palliative immunotherapy of cancer].

In addition to surgery, chemotherapy and radiation, immunotherapy of cancer resembles a potential treatment strategy for patients with cancer. To strengthen the immune system might help to control or even to eradicate malignant tumors. Immunoaugmentative strategies include biological response modifiers as interferons and interleukins. Recently, monoclonal antibodies directed against tumor associated antigens and coupled with radioisotopes or cytotoxic agents have become available. Adoptive immunotherapy uses immune effector cells, i.e. T-cells or natural-killer cells that are activated in-vitro by appropriate cytokines. Dendritic cells, either unstimulated or pulsed with tumor derived molecules have shown promising anticancer activity in selected tumors. Immunonutrition, that is the manipulation of immune phenomenons through edibles is a new and interesting topic. Immunologic strategies for the treatment of malignant diseases are currently under intensive preclinical and clinical investigation. Further insights into the mechanisms of host-defense against cancer cells and the modification of immune-effector cells might pave the way to efficient treatment strategies, even in the palliative setting.

Antibodies, Monoclonal↗
PubMed2001

Allogeneic or autologous stem cell transplantation (SCT) for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma: a single-centre experience.

PURPOSE OF THE STUDY: The aim of the study was to evaluate which patient might benefit most from allogeneic stem cell transplantation (SCT) in the treatment of relapsed and/or refractory lymphoma. PATIENTS AND METHODS: Thirty-eight consecutive lymphoma patients receiving either autologous (n = 24) or allogeneic (n = 14) stem cell grafts at our institution from 1986 to 1998 were retrospectively analysed regarding overall survival (OS), disease-free survival (DFS), transplant-related mortality (TRM), and relapse incidence (RI). Uni- and multivariate analyses were performed to identify patient characteristics predictive for outcome after SCT. RESULTS: The probabilities of OS, DFS, TRM, and relapse were 57%, 51%, 29%, and 30% following autologous and 43%, 43%, 29%, and 38% following allogeneic SCT. Disease status (sensitive versus refractory) and the time interval between diagnosis and SCT were the most powerful predictive parameters for OS and TRM, whereas elevated serum LDH levels were signifcant in determining relapse. CONCLUSIONS: In patients with elevated serum LDH levels and bone marrow involvement at the time of transplantation allogeneic was superior to autologous SCT and resulted in better outcome due to a lower relapse incidence strongly suggesting the existence of a graft-versus-lymphoma effect.

Adult↗
PubMed2001

Screening for Aspergillus spp. using polymerase chain reaction of whole blood samples from patients with haematological malignancies.

Sensitive screening for Aspergillus spp. using polymerase chain reaction (PCR) of whole blood samples in patients with haematological disorders has not been performed to date. In a 2-year study, 121 patients admitted to the University Hospital of Innsbruck for cancer chemotherapy without clinical signs of fungal infection were prospectively screened for Aspergillus spp. In 28 out of 121 (23%) patients, Aspergillus DNAaemia was detected. Of these patients, 16 (57%) were positive only once for Aspergillus DNA, but positivity was never associated with invasive aspergillosis. PCR positive episodes were short and resolved without antifungal treatment. Five patients (18%) had intermittent PCR positive results. Seven (25%) patients presented at least two consecutive positive PCR results; one of these patients developed invasive aspergillosis and another two were strongly suspected as having aspergillosis. Based on the criteria of the European Organization for Research and Treatment of Cancer case definitions, sensitivity and specificity of serial PCR monitoring were 75% and 96%. Positive PCR results became negative shortly after commencement of antifungal treatment, but the changes did not correlate with clinical responsiveness to treatment in three patients. Our results indicate the potential usefulness of PCR for screening for Aspergillus spp. in patients at risk, but without antifungal treatment.

Adult↗
PubMed2001

Palliative chemotherapy in pretreated patients with advanced cancer: oral trofosfamide is effective in ovarian carcinoma.

Thirty-four patients with advanced cancer of various origins and documented disease progression were treated with continuous daily doses of 50-150 mg of oral trofosfamide (TRO). Of 31 evaluable patients, 5 responded to this treatment (1 complete remission and 4 partial remissions) and 12 patients had stable disease. Four of 9 patients with advanced ovarian cancer resistant to platinum-containing regimens and paclitaxel responded to oral TRO. The median treatment duration was 26 weeks for responders and 6 weeks for nonresponders, with cumulative doses of up to 46.000 mg TRO. Response duration was 11-47 weeks. No significant side effects were observed. Oral TRO given in the outpatient setting seems to be an attractive therapeutic option for heavily pretreated cancer patients, and it has remarkable antitumor effects in patients with ovarian cancer.

Adult↗
PubMed2001

Optimal timing for the collection and in vitro expansion of cytotoxic CD56(+) lymphocytes from patients undergoing autologous peripheral blood stem cell transplantation.

To identify the optimal time for the collection of CD56(+) cytotoxic lymphocytes for adoptive immunotherapy in patients undergoing high-dose chemotherapy (HDCT) and peripheral blood stem cell (PBSC) transplantation, 18 breast cancer patients receiving either three cycles of epirubicin/paclitaxel (CT x 3) followed by HDCT and PBSC transplantation (n = 12) or CTx6 (n = 6) were studied. Blood samples were obtained before each CT/HDCT cycle, from PBSC collections, and repeatedly after autografting for up to 12 months. The number of CD56(+)3(-) and CD56(+)3(+) lymphocytes, their in vitro expandability with interleukin-2, and their cytotoxicity against MCF-7 and Daudi cells were analyzed. Six healthy females served as controls. CD56(+) cell counts in both treatment groups were subnormal but stable during the observation period. The cytotoxicity of the expanded CD56(+) cells was normal and unaffected by the treatment. The in vitro CD56(+) cell expandability (controls, 100 +/- 31-fold, mean +/- SEM) was normal before CT1 and CT2, but reduced in PBSC harvests performed after CT2 and application of G-CSF (21 +/- 6-fold; p < 0.01). After PBSC harvesting, the CD56(+) cell expandability increased to 185 +/- 74-fold and 170 +/- 69-fold (before CT3 and HDCT). This increase was not observed in those patients who did not undergo PBSC mobilization. Two weeks after autografting, the CD56(+) cell expandability was minimal (6 +/- 1-fold), and recovered to 34 +/- 6-fold. Thus, CT, HDCT and autografting do not alter the frequency and inducible cytotoxicity of CD56(+) cells in breast cancer patients. However, the proliferative capacity of CD56(+) cells obtained from PBSC harvests and after autografting is impaired. Therefore, instead of the PBSC graft, maximally expandable CD56(+) cells obtained at least 1 week after PBSC collection should be considered for adoptive immunotherapy after PBSC autografting.

Adult↗
PubMed2000

Ep-CAM overexpression in breast cancer as a predictor of survival.

The epithelial glycoprotein Ep-CAM is overexpressed in colon cancer and breast cancer. We assessed the frequency and prognostic significance of Ep-CAM in tissue specimens from 205 patients with invasive breast cancer, by immunohistochemical staining with a monoclonal antibody specific for the Ep-CAM antigen. Ep-CAM overexpression was found in 35.6% of samples and was associated with poor disease-free and overall survival.

Antigens, Neoplasm↗
PubMed2000

Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of VEGF during bacterial meningitis, VEGF was measured in cerebrospinal fluid (CSF) and blood of 37 patients with bacterial meningitis and 51 control patients, including 16 patients with viral meningitis. Circulating VEGF levels were similar in bacterial meningitis patients and control patients. VEGF(CSF) was detected in 11 (30%) of 37 of bacterial meningitis patients (range, <25-633 pg/mL) but in none of the control patients. The median VEGF index was 6.2 (range, 0.6-42), indicating intrathecal production. Median CSF cell counts, protein levels, and CSF: serum albumin ratios were higher for patients with detectable VEGF(CSF), although the difference was not statistically significant. VEGF immunoreactivity in autopsy brain specimens was found in the inflammatory infiltrate of patients with bacterial meningitis. These results indicate that inflammatory cells secrete VEGF during bacterial meningitis and that VEGF may contribute to blood-brain barrier disruption.

Adolescent↗
PubMed2000

Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.

BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis. METHODS: We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens. FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium. INTERPRETATION: These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.

Adult↗
PubMed2000

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Adolescent↗
PubMed2000

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression.

Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum. Samples were collected from 14 patients with primary brain tumors of various histology (six glioblastomas, one protoplasmatic astrocytoma, two pilocytic astrocytomas, one ependymoma, one meningioma, and three craniopharyngiomas) and two patients with solitary cystic brain metastases from adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic lung cancer the concentration of VEGF in serum and cyst fluid was determined during disease progression. During 60 days of follow-up VEGF concentrations in the cyst fluid collected by puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive VEGF is produced at the tumor site and abundantly released into the cyst fluid of primary and metastatic brain tumors. Interestingly, this abundant local release is not reflected in serum VEGF levels, even in the case of very high VEGF concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the formation of tumor cysts in brain tumors and correlates with local disease progression.

Adolescent↗
PubMed2000

Treatment of patients with advanced chronic myelogenous leukemia with interferon-alpha-2b and continuous oral cytarabine ocfosfate (YNK01): a pilot study.

The efficacy of continuous oral cytarabine ocfosfate (YNK01) (300 mg/day) in combination with interferon alpha (IFNalpha, 5x10(6) IU/day) was evaluated in patients with advanced chronic myelogenous leukemia, who previously failed to respond to IFNalpha-based therapies. Dose escalations up to 900 mg YNK01 were allowed in patients who failed to respond. In view of our results, four patients developed a complete hematological response after YNK01 was started. Among those who initially responded to YNK01, one complete cytogenetic response was achieved 18 months later. Although the data are preliminary, this is the first study showing that continuous administration of YNK01 along with IFNalpha is effective in patients with advanced chronic myelogenous leukemia.

Adult↗
PubMed2000

Mammaglobin gene expression: a superior marker of breast cancer cells in peripheral blood in comparison to epidermal-growth-factor receptor and cytokeratin-19.

Various molecular markers have been used for the detection of circulating breast cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). Using nested RT-PCR, we compared the specificity and sensitivity of human mammaglobin (hMAM), epidermal-growth-factor receptor (EGF-R), and cytokeratin 19 (CK-19) expression as markers for circulating carcinoma cells in the peripheral blood of patients with breast cancer. Blood samples from 12 patients with ductal carcinoma in situ, 133 patients with invasive breast cancer, 20 patients with hematological malignancies, 31 healthy volunteers, and tumor tissues from 40 patients with invasive breast cancer were screened for mRNA encoding hMAM, EGF-R, or CK-19 by nested RT-PCR. In all breast cancer tissues, mRNA for hMAM, EGF-R, and CK-19 was detectable. In blood samples from patients with invasive breast cancer, 11 (8%), 13 (10%), and 64 (48%) were positive for mRNA encoding hMAM, EGF-R, or CK-19, respectively. Blood samples from none of the healthy volunteers and patients with hematological disorders were positive for hMAM, while CK-19 mRNA was found in the blood of 12 (39%) healthy volunteers and transcripts for EGF-R and CK-19 were detectable in 5 (25%) and 2 (10%), respectively, of the patients with hematological malignancies. Only hMAM mRNA expression in blood correlated with clinical parameters such as nodal status, metastasis, and CA 15-3 serum levels. In summary, hMAM transcripts detectable in blood by RT-PCR represent the most specific molecular marker for hematogenous spread of breast cancer cells. With the nested RT-PCR method, aberrant EGF-R mRNA expression might occasionally be found in hematological malignancies, whereas CK-19 mRNA expression proved to be rather nonspecific. The prognostic value of hMAM RT-PCR-based tumor cell detection in peripheral blood should be further tested and validated in prospective studies.

Adult↗
PubMed2000

Evaluation of optimal survival of primitive progenitor cells (LTC-IC) from PBPC apheresis products after overnight storage.

Optimal overnight (ON) storage of PBPC aphereses is becoming an increasingly important issue and different options for storing PBPC products exist. The survival of primitive progenitor cells is of major interest, as recent data suggest that these progenitors are not only important for long-term engraftment but also contribute significantly to the early phase of hematopoietic engraftment after myeloablative therapy. We therefore investigated the survival of primitive progenitor cells (ie long-term culture initiating cells, LTC-IC) before (ie within 2 h after finishing the apheresis procedure) and after ON storage lasting 16 to 20 h. In addition, we compared the % of recovery of LTC-IC with that of mature progenitors (ie colony-forming cells, CFC) and with the % viability of the mononuclear cells in the apheresis product. Aliquots of PBPC aphereses products were tested in collection bags at room temperature (RT), in EDTA tubes both at RT or 4 degrees C +/- the addition of autologous plasma (AP; 2.6-fold the apheresis volume) and +/- the possibility of gas exchange. Mean viable cell counts did not show strong differences between the different storage conditions and were poor predictors for the survival of CFC and LTC-IC. At RT (collection bags, EDTA tubes +/- gas exchange) recoveries (% of input) of both, CFC (18%, 18% and 31%) and LTC-IC (10%, 4%, 17%) were low. The addition of AP at RT improved the survival of CFC and LTC-IC to 66% and 38%, respectively. Optimal recoveries for both types of progenitors (CFC: 99%, LTC-IC: 109%) were obtained at 4 degrees C in the presence of AP. In addition, a good correlation between the survival of CFC and LTC-IC was obtained (r = 0.76) suggesting that the analysis of CFC may also allow some conclusions to be drawn on the survival of LTC-IC. Bone Marrow Transplantation (2000) 25, 197-200.

Blood Component Removal↗
PubMed2000

Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood.

Serum levels of vascular endothelial growth factor (VEGF-S) have been reported to correlate with tumor stage and prognosis in various human malignancies. The source of soluble VEGF in peripheral blood remains obscure. We therefore measured the concentration of immunoreactive VEGF in 241 serum samples and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation between the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but not VEGF-P was found. VEGF-S levels were 58.43 +/- 42.50 pg/ml (mean +/- SD) in patients with a PC < 50 x 10(9)/l, 203.29 +/- 176.56 pg/ml for a PC of 50-150 x 10(9)/l, and 457.42 +/- 475.41 pg/ml for a PC > 150 x 10(9)/l. Interestingly, VEGF-P levels were substantially lower than the corresponding VEGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of the platelets very high VEGF levels were found. The VEGF content per 10(9) platelets was calculated at 2.51 +/- 2.39 pg and was dependent on the mean platelet volume. In summary, VEGF release from platelets during blood clotting was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in peripheral blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the diagnostic and prognostic value of VEGF-S in cancer patients must be interpreted with caution. Our data provide the basis for predicting VEGF-S in relation to PC in vivo, and for reevaluating former studies of VEGF-S in patients with malignant or nonmalignant disease.

Adult↗