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Biomedical subjects

W Dippold

Publications and source records attributed to W Dippold.

At least 19 recordsLinked to original sources
PubMed1998

[Palliative chemotherapy in metastatic and locally advanced gastrointestinal tumor].

Systemic chemotherapy ensures better quality of life than supportive treatment alone in incurable patients. Mean survival for the total group of patients with gastric, pancreatic and colorectal cancer can be extended only by months, however, this does not preclude that in individual cases survival time may reach years. The future of tumor therapy consists in sooner treatment of early stages and improved adjuvant therapeutic methods.

Antineoplastic Agents↗
PubMed1997

[Prostate carcinoma associated spontaneous factor VIII:C inhibitor hemophilia. Successful therapy of severe hemorrhagic complication with porcine factor VIII in a 75-year-old patient].

Inhibitors of factor VIII are a rare condition in non-hemophiliacs, but they are frequently responsible for life threatening hemorrhage. Acquired factor VIII:C inhibitors represent the spontaneous development of autoantibodies that partially or completely neutralize the plasma coagulant activity of the clotting factor. The autoantibodies can arise in diverse clinical settings, in older adults they are frequently associated with immunologic disorders or malignancies. We report of a 75-year-old man with acquired factor VIII:C inhibitor associated with adenocarcinoma of the prostate and a successful treatment of a severe bleeding complication with porcine factor VIII. A 75-year-old man was admitted because of a hematoma of his right cheek and an isolated prolonged aPTT. Acquired factor VIII:C inhibitor was identified as the cause and immuno-suppressive therapy was begun. In the clinical course severe hemorrhaging occurred and was successfully treated with porcine factor VIII (Hyate:C). The initially high inhibitor titer of 32 Bethesda Units (BU) disappeared. As the cause of acquired factor VIII:C inhibitor a newly diagnosed adenocarcinoma of the prostate is likely. After complete remission of acquired factor VIII:C inhibitor radiation therapy was begun. Six months after severe hemorrhaging the patient was clinically stable and PSA levels were normal. This case demonstrates the necessity of a precise diagnosis and therapy regimen of this coagulopathy based on clinical and laboratory data. In the absence of hemorrhage immuno-suppressive therapy with corticosteroids is indicated, in a patient with severe bleeding and high inhibitor titer (> or = 5 BU) porcine factor VIII should be administered.

Adenocarcinoma↗
PubMed1997

Chemotherapy in advanced pancreatic cancer.

Patients with advanced adenocarcinomas of the pancreas have an exceptionally poor prognosis. Modest activity has been demonstrated with single agents (response rates of 25% at best with 5-fluorouracil [5-FU] and mitomycin). Better results have not been obtained by combination chemotherapy. Improvements in the palliation have been achieved by treatment with 5-FU, folinic acid (FA), and interferon-alpha-2A (IFN-alpha) weekly in the context of a phase II trial. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR), and 28 (49%) had no change of disease (NC). The median survival time was 10 mo for patients with progressive disease. Twenty-two out of 36 patients with tumor-related pain whose tumors were affected in terms of PR, MR, and NC became free of pain during treatment. Fever (56%), nausea (37%), and diarrhea (33%) were common toxicities observed. Therefore, biochemical modulation of 5-FU with FA and IFN-alpha shows some positive effects in the treatment of pancreatic cancer with moderate toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

The 9-O-acetylated disialosyl carbohydrate sequence of CDw60 is a marker on activated human B lymphocytes.

Gangliosides with a terminal 9-O-acetylated disialosyl group (CDw60 structures) show a restricted surface expression on human leukocytes. Hithereto, they have only been detected on subpopulations of human T lymphocytes. Using the defined CDw60 antibody UM4D4 and two new antibodies with preferential CDw60 activities, F6 and Z17, we demonstrate for the first time that CDw60 is an activation marker on human B lymphocytes. In vitro phorbol ester-stimulated human peripheral blood B lymphocytes as well as in vivo activated tonsillar B lymphocytes became CDw60 positive. CDw60 expression of these cells exceeds that of resting and activated T-lymphocytes.

Acetylation↗
PubMed1996

alpha(1,3)Fucosyltransferase expression in E-selectin-mediated binding of gastrointestinal tumor cells.

E-selectin recognizes the oncofetal antigen sialyl-Lewis X, which is highly expressed in adenocarcinoma. Five alpha(1,3)fucosyltransferases (FT) have been cloned that confer cell-surface expression of sialyl-Lewis X on transfected cells. We show here that 12/18 gastrointestinal-tumor cell lines bind specifically to immobilized E-selectin and that in sialyl-Lewis-X-positive cells binding is inhibited with a monoclonal antibody against sialyl-Lewis X. Using RT-PCR, we determined the expression of the alpha(1,3)fucosyltransferases III, IV, V, VI and VII in gastrointestinal tumor cells. Transcripts of FT IV and FT VII are abundantly expressed in all tested cells. Therefore no single fucosyltransferase could be correlated with the expression of sialyl-Lewis X and the ability of the tumor cells to bind to E-selectin. The data suggest that in gastrointestinal-tumor cells sialyl-Lewis X is necessary but not sufficient for E-selectin binding.

Base Sequence↗
PubMed1996

Elevated serum E-selectin in patients with liver metastases of colorectal cancer.

E-selectin, an endothelial cell adhesion molecule, mediates the initial step of leucocyte adhesion to activated vascular endothelium. The soluble isoform of E-selectin promotes angiogenesis in rat cornea. In the present study, we investigated whether leucocyte adhesion and angiogenesis are also involved in tumour progression and metastasis of colorectal cancer. Therefore, we determined the level of circulating soluble E-selectin in serum samples of 38 patients with colorectal cancer; 20 patients with non-metastatic and 18 patients with metastatic disease. Median levels of soluble E-selectin were found to be significantly higher in metastatic tumour disease (88.7 ng/ml, range 25-203 ng/ml) than in healthy controls (34.9 ng/ml, range 15-59 ng/ml, P = 0.01), in patients with primary tumours or with local recurrences (39.5 ng/ml, range 22-100 ng/ml). Furthermore, there was no correlation with the serum level of C-reactive protein, fibrinogen or tumour necrosis factor alpha suggesting that the elevation of E-selectin is independent of inflammation in tumour patients. Therefore, we propose that elevated soluble E-selectin may reflect increased neovascularisation in metastatic tumour tissue.

Adult↗
PubMed1996

Activity of the DNA repair protein O6-methylguanine-DNA methyltransferase in human tumor and corresponding normal tissue.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main determinant of resistance of cells towards the cytostatic effect of N-nitrosoureas. Here we report the activity of MGMT in different types of human tumors. Colorectal tumors showed the highest mean of MGMT activity (481 +/- 258 fmol/mg protein) followed by ovarian tumors (437 +/- 291 fmol/mg), breast (306 +/- 204 fmol/mg), testicular (299 +/- 179 fmol/mg), and brain tumors (55 +/- 44 fmol/mg). Only in breast and brain tumors were MGMT-deficient samples found, with a frequency of 3 and 5%, respectively. No significant difference in mean MGMT activity was observed between breast tumors of grading I, II, and III. For brain tumors there was a tendency of MGMT to decline with increasing grading. Breast and colorectal carcinomas were compared with the corresponding normal tissue obtained from the same patient. The data showed for 11 out of 12 pairs of breast tissue and for 13 out of 15 pairs of colorectal tissue that MGMT activity in the tumor was equal to or, more frequently, higher than the activity found in the corresponding normal tissue. Thus, it appears that in these groups of tumors, increase of MGMT activity during tumor formation and progression is the rule rather than the exception.

Brain Neoplasms↗
PubMed1995

7-O-acetyl-GD3 in human T-lymphocytes is detected by a specific T-cell-activating monoclonal antibody.

The monoclonal antibody U5, which is a potent inducer of proliferation in human T-cells, was found to bind to an alkali-sensitive derivative of ganglioside GD3. Using immunochemical and spectroscopic methods, the structure of the U5 antigen was determined as 7-O-acetyl-GD3. The antibody U5 did not react with 9-O-acetyl-GD3 and bound severalfold more stronger to 7-O-acetyl-GD3 than to GD3. U5 is the first antibody known to detect preferentially 7-O-acetyl-GD3. Flow cytometric analysis showed that each major class of human leukocytes contained a significant fraction of cells binding the U5 antibody.

Animals↗
PubMed1995

Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial.

Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients (23%) had progressive disease (PD). The median survival time was 10 months for all patients, 22 months for patients with partial remission and 5 months for patients with progressive disease. Many patients with tumour-related pain whose tumours were affected in terms of PR, MR, NC were free of pain during treatment with this regimen (22/36 patients). The common toxicities observed were fever (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical modulation of 5-FU with FA and IFN-alpha has some positive effects in the treatment of pancreatic cancer of moderate toxicity.

Adenocarcinoma↗
PubMed1995

Combination 5-fluorouracil (FU), folinic acid (FA), and alpha-interferon 2B in advanced gastric cancer: results of a phase II trial.

BACKGROUND: Based on encouraging treatment results with FU/FA or FU/IFN in gastrointestinal tract cancer, a phase II study was conducted to evaluate the effects and toxicity of combination FU/FA/IFN in patients (pts) with inoperable/metastatic gastric cancer. PATIENTS AND METHODS: IFN 6 M.U. s.c. 1 x/week, FU 500 mg/m2 bolus i.v. 1 x/week and FA 500 mg/m2 1 x/week as a 2-hour infusion. Of 72 treated pts, 72 (22 females, 50 males) are evaluable for response and toxicity. Median age was 55.6 years (28-80), and median Karnofsky performance status was 80% (70-100). Sites of measurable disease were inoperable primary tumors/local recurrence (18), liver metastasis (22), lymph nodes (31) and peritoneum (20). One pt had bone marrow metastasis and another had paraneoplastic hyperfibrinolytic coagulopathy. RESULTS: 10/72 pts had complete response, 20/72 pts partial response, 40/72 pts tumor stabilization and 2/72 pts progressive disease. The median duration of response (CR/PR) was 9 months, the median progression-free interval 6 months, the median survival time was 9 months, and for responding patients (CR/PR) 12.5 months. TOXICITY: 1/72 pts had WHO grade 4 toxicity (diarrhea), 5/72 pts had WHO grade 3 toxicity (nausea 1, diarrhea 4). Except for 1 treatment-limiting grade 4 toxicity, no modifications of dose or schedule due to toxicity were required. Thirty-six of 44 pts experienced a significant reduction in tumor-related pain under treatment. CONCLUSION: Biochemical modulation of FU with FA and IFN is effective in advanced gastric cancer. Moderate toxicity, outpatient treatment setting and high rates of amelioration tumor-related pain contribute to an effective palliation.

Adult↗
PubMed1995

Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.

The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells indicating that the GD3 molecule is not a marker for a certain functional T cell subset. In contrast to anti-CD3 mediated activation, the responsiveness of T cells to stimulation via GD3 was dependent on the cell surface expression of the molecule and could be enhanced by costimulation via CD2, CD3, CD26 or CD28. In addition, anti-GD3 antibodies delivered a potent costimulatory signal for antigen-induced proliferation of CD4+ T lymphocytes. In summary, our experiments illuminate the mechanisms of anti-GD3 antibody induced T cell activation.

Antibodies, Monoclonal↗
PubMed1994

Inhibition of anti-GD3-ganglioside antibody-induced proliferation of human CD8+ T cells by CD16+ natural killer cells.

The ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4+ and CD8+ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8+ and CD4+ T cells of normal donors containing less than 5% CD16+ natural killer (NK) cells. In contrast to CD4+ T cells, CD8+ T cells proliferated only weakly in the presence of 15% CD16+ NK cells. The proliferative response of purified CD4+ and CD8+ T cells (< 5% NK cells) correlated with the antibody-dependent induction of integral and soluble interleukin-2 (IL-2) receptors and was reduced to 20% by an anti-IL-2 receptor antibody. Our results show, that the GD3 molecule represents an activation molecule for both CD4+ and CD8+ T cells and that CD16+ NK cells selectively inhibit anti-GD3 antibody-induced proliferation of CD8+ T cells.

Antibodies, Monoclonal↗
PubMed1994

Sustained elimination of hepatitis B virus from serum induced in a patient with chronic hepatitis B and advanced human immunodeficiency virus infection.

A 48-year-old male patient was admitted with acquired immunodeficiency syndrome (stage III, Centers for Disease Control 1993) and viremic hepatitis B. Blood CD4 count was 15/microliters. Discontinuation of prednisolone, previously prescribed by the patient's family practitioner because of elevated liver enzymes, resulted in severe hepatitis (alanine aminotransferase > 300U/l). Administration of interferon-alpha (9 x 10(6) U s.c. 3 x weekly) was initiated. Serum markers of viral replication disappeared, and aminotransferase levels returned to normal within a few weeks. The patient's serum was found negative for HBsAg after 3 months. Immunohistochemical analysis of liver biopsies before and during interferon therapy showed disappearance of all hepatitis B virus antigens and a marked reduction in inflammatory activity. Hepatitis B virus seroconversion remained stable until the patient died from the syndrome 2 years later. This case shows that in spite of severe HIV-associated immune deficiency with CD4 counts constantly below 100/microliters, interferon-alpha can lead to sustained serological and histological improvement of viremic hepatitis B. Previous administration and discontinuation of cortisone may have helped to reach this effect.

AIDS-Related Opportunistic Infections↗
PubMed1994

Immunological response to intrathecal and systemic treatment with ganglioside antibody R-24 in patients with malignant melanoma.

Murine monoclonal antibody (MAb) R-24 reacts with the ganglioside GD3 that is highly expressed on malignant melanoma. 2 patients with melanosis of the meninges received MAb R-24 intrathecally. Regressive changes in tumour cells were observed in both patients after intrathecal application of MAb R-24 (1-10 mg, 8-10 h, over 5-6 weeks). The first patient suffered from brain metastases and died a few weeks later, whereas the second achieved a complete remission with no evidence of disease 6 years after intrathecal R-24 treatment. No R-24-related neurotoxicity has occurred to date. The administration of MAb R-24 caused an increase of inflammatory cells in the cerebrospinal fluid (CSF) of both patients. Cytotoxic lymphocytes, cultured from the CSF, showed high cytolytic activity against allogeneic melanoma cells in vitro. In addition, 15 patients with advanced melanoma, in which the brain was not affected, were treated with R-24 intravenously using high dose R-24 (5 or 10 mg/m2) or low dose R-24 (1 mg/m2). No remissions were registered in the high dose group, with only 1/6 patients experiencing a mixed response. In contrast, 2/9 patients treated with low dose R-24 achieved a partial remission, one achieving a minor response and the other a mixed response. Toxicity was related to the dose of R-24 administered. Urticaria, burning and pruritus were the prominent side-effects, mostly occurring at the high dose level. Immunological monitoring during and after intravenous treatment showed no significant changes in peripheral blood lymphocytes, natural killer cell activity or antibody-dependent cellular cytotoxicity, although transient changes were observed. There was no correlation between immunological parameters and clinical response.

Adult↗