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Wolfram Trudo Knoefel

Publications and source records attributed to Wolfram Trudo Knoefel.

8 recordsLinked to original sources
PubMed2006

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker.

BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.

Antigens, Neoplasm↗
PubMed2005

Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration.

The liver has a large capacity for regeneration after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSCs) to participate in liver regeneration. Here we report on three patients subjected to intraportal administration of autologous CD133(+) BMSCs subsequent to portal venous embolization of right liver segments, used to expand left lateral hepatic segments as FLRV. Computerized tomography scan volumetry revealed 2.5-fold increased mean proliferation rates of left lateral segments compared with a group of three consecutive patients treated without application of BMSCs. This early experience with portovenous application of CD133(+) BMSCs could suggest that this novel therapeutic approach bears the potential of enhancing and accelerating hepatic regeneration in a clinical setting.

AC133 Antigen↗
PubMed2004

Malignant fibrous histiocytoma of the extremities and trunk: an institutional review.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common subtype of soft-tissue sarcoma. Detailed understanding of this tumor type may lead to improved therapeutic strategies. METHODS: An institutional review was performed on all patients with primary MFH of the extremities and trunk operated on between 1988 and 2000. RESULTS: Ninety-seven patients with histologically confirmed MFH (G1, n=8; G2, n=25; G3, n=64) were analyzed. Local recurrence was 31% after a median of 13 months. Distant metastases occurred in 29 patients (30%). After a median follow-up of 4.5 years, 54 patients were alive without evidence of disease; median survival time was 84 months at a cumulative 5-year survival rate of 70%. Tumor size significantly influenced disease-free survival (T2 vs T1, P<.01, risk ratio [RR] 6.0), as did tumor depth (subfascial tumors, P<.01, RR 3.1) and presence of positive lymph nodes (P=.02, RR 6.9). Positive microscopic margins and subfascial tumors were associated with an increased local recurrence rate (RR 4.8, P<.001 and RR 3.5, P=.02, respectively). Significant multivariate risk factors of distant metastases were tumor size, depth, and grade. Though not performed in a randomized fashion, a subgroup analysis indicated that adjuvant radiation therapy significantly reduced local tumor failure. CONCLUSION: We conclude that aggressive, albeit limb-preserving resection of MFH, should be performed at initial operation to minimize risk of local recurrence; a strict follow-up especially of subfascial tumors should be performed.

Abdominal Neoplasms↗
PubMed2002

Cytotoxic T lymphocyte mediated recognition of human pancreatic cancer cells.

T lymphocytes play an important role in tumor rejection and their response to human malignant melanoma has been well documented. In contrast, the existence of cytotoxic T lymphocytes (CTL) to pancreatic cancer remains unclear. Tumor-associated lymphocytes (TAL) and peripheral blood monocytes (PBMC) were isolated from pancreatic cancer patients. Tumor-specific CTL were generated from TAL and PBMC using solid-phase anti-CD3, low-dose IL-2 (50 IU/ml) and repetitive autologous tumor stimulation. The specificity of CTL was tested in standard cytotoxicity assays using autologous tumor cells, autologous fibroblasts when available, several allogeneic pancreatic tumor cells and the NK-sensitive cell line K562. Anti-HLA-Class I MAb, W6/32, was used to demonstrate that tumor-specific CTL were HLA-Class I restricted. HLA-molecules of human pancreatic cancer cells were washed out using acid elution. Eight consecutive, histologically confirmed pancreatic cancer specimen as well as peripheral blood mononuclear cells were analyzed. CTL were capable of lysing autologous tumor cells significantly after 3 stimulations with autologous tumor cells. T cell mediated recognition was HLA-Class I restricted as shown by incubation with MAb anti-HLA-Class I. In case of HLA-A2 positivity, incubation of tumor cells in cytotoxicity assays resulted in significant inhibition. Autologous fibroblasts or K562 cells were lysed significantly less. HLA-Class I molecule elution resulted in significantly lower recognition of these cells by CTL. These results show for the first time in a larger series the possibility of generating CTL in human pancreatic cancer. The identification of new tumor associated antigens or tumor antigens will be crucial for establishing new treatment strategies.

Adenocarcinoma↗
PubMedDate not supplied

Comparison of various sources of antigen-presenting cells for the generation of GP2-tumor peptide specific cytotoxic T-lymphocytes.

BACKGROUND: The need for new therapeutic regimens for cancer has led to the identification of tumor antigens in several tumors. Yet, potent antigen-presenting cells (APC) are being identified and characterized in order to find those most able to induce T-cell-mediated immunity. To facilitate the generation of cytotoxic T-lymphocytes (CTL) specific for known antigens, various sources of antigen-presenting cells (APC) were compared for their efficiency. MATERIALS AND METHODS: Allogeneic dendritic cells (DC), T2 cells and two Epstein Barr virus-transformed B cell lines, JY and TK-6, were used as antigen-presenting cells (APC). T-cells from normal donors were stimulated with solid-phase anti-CD3 antibody and reactivated with peptide-pulsed APC three times at weekly intervals. To minimize any potential alloreactivity, eighteen random combinations of JY, TK6 and T2 were used for three peptide stimulations. The APC were pulsed with the HLA-A2-binding HER2/neu-derived tumor antigen p654-662 (GP2). RESULTS: In addition to either T2 or DC alone, most combinations of APC induced significant recognition of GP-2-pulsed target cells to a varying degree. The stimulation index varied from 0.5 to 8.1 using combinations of APC. The level of peptide recognition correlated with recognition of HLA-A2+, HER2/neu+ pancreatic cancer cells; in contrast, HLA-A2-negative pancreatic cancer cells were not recognized. The recognition of tumor cells was HLA-restricted as evidenced by blocking studies with anti-HLA class I and anti-HLA-A2 antibodies. CONCLUSION: Tumor peptide-specific CTL can be generated using allogeneic B cell lines, which may provide a useful alternative to T2 or dendritic cells.

Antigen-Presenting Cells↗
PubMedDate not supplied

CD44s expression is associated with improved survival in soft tissue sarcoma.

Expression of CD44 has been identified as a prognostic factor in several malignant diseases. Few studies have correlated CD44 expression in soft tissue sarcoma with subsequent tumor progression or recurrence. We sought to investigate the clinical significance of CD44s (standard) in adult soft tissue sarcoma (STS). Tumor specimens of 62 patients with STS were evaluated by immunohistochemistry for CD44s expression. The primary outcome measures were survival and local recurrence. Of 62 analyzed specimens, 49 tumors were CD44s-positive compared to 13 CD44s-negative tumors. Kaplan-Meier survival analysis indicated significantly better survival among patients whose tumor was CD44s-positive (p=0.015). CD44s expression (hazard ratio, 3.1; 95% confidence interval, 1.5 to 7.0), tumor size (hazard ratio, 11.7; 95% confidence interval, 1.8 to 322) and resection quality (R1 vs. R0: hazard ratio, 8.7; 95% confidence interval, 3.1 to 24.5) were independent predictors of survival in multivariate analysis. CD44s expression correlates with prognosis of soft tissue sarcomas and therefore may have a pathogenetic role in tumor progression. Our results suggest that expression of CD44s in primary STS provides value regarding the progression of STS and, therefore, could be useful in selecting patients for adjuvant treatment.

Adult↗