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A Baars

Publications and source records attributed to A Baars.

13 recordsLinked to original sources
PubMed2005

Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage melanoma patients.

PURPOSE: To study the effect of autologous tumor cell vaccinations on the presence and numbers of circulating CD8+ T cells specific for tumor-associated antigens (TAA) in metastatic melanoma patients. To investigate the correlation between the presence of tumor-infiltrating lymphocytes (TIL) and circulating TAA-specific CD8+ T cells before and after autologous tumor cell vaccination with overall survival. EXPERIMENTAL DESIGN: Twenty-five stage III and resected stage IV metastatic melanoma patients were adjuvantly treated with a series of intracutaneously injected autologous tumor cell vaccinations, of which the first two contained BCG as an immunostimulatory adjuvant. Tumor samples and blood samples obtained before and after vaccination of these patients were studied for the presence of TAA-specific T cells using HLA-tetramers and results were correlated with survival. RESULTS: In 5 of 17 (29%) melanoma patients, circulating TAA-specific T cells were detectable prior to immunizations. No significant changes in the frequency and specificity were found during the treatment period in all patients. Presence of circulating TAA-specific T cells was not correlated with survival (log rank, P=0.215). Inside melanoma tissue, TAA-specific TIL could be detected in 75% of 16 available tumor samples. In case of detectable TAA-specific TIL, median survival was 22.5 months compared to median survival of 4.5 months in case of absence of TAA-specific T cells (log rank, P=0.0094). In none of the patients, TAA-specific T cells were found both in tumor tissue and blood at the same time. CONCLUSIONS: These data suggest that the presence of TAA-specific TILs forms a prognostic factor, predicting improved survival in advanced-stage melanoma patients. The absence of TAA-specific T cells in the circulation suggests that homing of the tumor-specific T cell population to the tumor site contributes to the effectiveness of antitumor immunity.

Adjuvants, Immunologic↗
PubMed2003

[Good response to treatment with the selective tyrosine-kinase inhibitor imatinib in a patient with metastatic dermatofibrosarcoma protuberans].

A 37-year-old man was diagnosed with metastatic dermatofibrosarcoma. Dermatofibrosarcoma protuberans is a rare skin tumour with a strong tendency for infiltrative growth, resulting in a high rate of local recurrences; metastatic disease develops in approximately 5% of patients, especially in the lungs. On the basis of some recent publications about the use of imatinib in patients with dermatofibrosarcoma, the patient was prescribed this drug. The treatment resulted in a partial response. Imatinib is the first registered selective tyrosine-kinase inhibitor for treatment of chronic myeloid leukaemia. The inhibition of tyrosine kinase interrupts the proliferative signal transduction.

Adult↗
PubMed2002

[Metabolic disregulation after starting feeding: "refeeding" syndrome: the central role of phosphate].

A 47-year-old man was admitted due to serious weight loss after several months in which he had not eaten and had drunk almost solely beer. Shortly after the start of enteral tube feeding, the patient developed serious heart failure. This was associated with severely disrupted electrolyte levels and in particular hypophosphataemia and hypomagnesaemia. This condition is termed refeeding syndrome. The circulating volume increases due to the hyperinsulinaemia which occurs during the feeding phase. Furthermore a shortage of ATP occurs and the heart may fail. In efforts to establish feeding, a weight increase of not more than 1 kg per week should be attempted; if the weight increases by more than this, then fluid retention is the probable cause.

Alcohol Drinking↗
PubMed2002

A phase II study of active specific immunotherapy and 5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma.

Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40-50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity.

Adult↗
PubMed2001

Adjuvant treatment of colorectal cancer: towards tumor-specific immunotherapies.

Colorectal cancer is one of the leading causes of cancer-related mortality. After a series of clinical trials, the adjuvant 5-FU based chemotherapy has established a definitive role in the management of stage III colon cancer. The precise role for chemotherapy in stage II disease remains under investigation and less toxic treatment modalities like active specific immunotherapy have emerged as potentially attractive alternatives. It is most likely that the adjuvant treatment of colon cancer will move towards more tumor-specific immunotherapies using antibody- or vaccination-based strategies. Phase II/III clinical trials investigating these different modalities in colorectal cancer are reviewed.

Adenocarcinoma↗
PubMed2000

Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: experience in 81 patients.

BACKGROUND: Currently there is no standard adjuvant treatment following surgical resection of metastatic melanoma. We investigated whether surgery followed by autologous tumor cell-BCG vaccination was beneficial for malignant melanoma patients. In this study we focus on the prognostic value of DTH response following vaccination therapy. PATIENTS AND METHODS: Eighty-one patients with AJCC stage III and IV melanoma were selected. Whenever feasible, radical metastasectomy was performed. ASI was initiated by the administration of three weekly intra-cutaneous vaccinations with 10(7) irradiated autologous tumor cells, starting four weeks after surgery. Depending on the size of DTH response to the first three injections, subsequent vaccinations were planned. The first two vaccines also contained 10(7) BCG organisms as an immune stimulatory adjuvant. RESULTS: Induration as well as erythema correlated strongly with survival (P < 0.0001 and P = 0.0004). After radical metastasectomy in stage III melanoma patients a five-year survival of 48% was observed. In stage IV disease, a five-year survival of 34% was seen, after radical surgery had been performed. When macroscopic disease was present at start of vaccination treatment, no clinical responses occurred. Apart from transient skin ulceration at the site of BCG-containing vaccinations, no serious side effects were observed. CONCLUSIONS: This study shows that large-scale preparation of autologous melanoma cell vaccines is feasible. while vaccination results in DTH responses that correlate significantly with survival. ASI seemed to be beneficial in stage III and stage IV melanoma when given in the adjuvant setting, while causing only very mild side effects.

Adjuvants, Immunologic↗
PubMed1991

Five-day 4'-(9-acridinylamino)methanesulphon-m-anisidide and intermediate-dose cytosine arabinoside in high-risk relapsing or refractory acute myeloid leukemia.

Twenty-two patients with acute myeloid leukemia (AML), having a median age of 48.3 years (range 26-70; 10 male, 12 female), were treated with 4'-(9-acridinylamino) methanesulphon-m-anisidide (m-AMSA) 100 mg/m2 and cytosine arabinoside (AraC) 2 x 1000 mg/m2i.v. on days 1-5. There were 2M1,8 M2, 9 M4, 2M4 Eo, and 1 M5a. Of these, 12 achieved a complete remission, 3 a partial remission and 6 did not respond. The median remission duration was 9.0 months and the median overall survival 8.1 months. Side-effects of induction consisted mainly of haematological toxicity and infections with a median duration of WHO-grade-4 granulopenia and thrombopenia of 20 and 28 days respectively. Organ toxicity was mild with mucositis and cutaneous and liver toxicity being experienced by only a few patients. There was one treatment-related death. Five-day m-AMSA and intermediate-dose AraC is an easy-to-handle condensed treatment schedule with tolerable toxicity. Its effectiveness in relapsed and refractory AML is comparable to combinations of high-dose AraC with m-AMSA, anthracyclines or etoposide.

Acute Disease↗
PubMed1986

Negative staining and immunoelectron microscopy of adhesion-deficient mutants of Streptococcus salivarius reveal that the adhesive protein antigens are separate classes of cell surface fibril.

The subcellular distribution of the cell wall-associated protein antigens of Streptococcus salivarius HB, which are involved in specific adhesive properties of the cells, was studied. Mutants which had lost the adhesive properties and lacked the antigens at the cell surface were compared with the parent strain. Immunoelectron microscopy of cryosections of cells labeled with affinity-purified, specific antisera and colloidal gold-protein A complexes was used to locate the antigens. Antigen C (AgC), a glycoprotein involved in attachment to host surfaces, was mainly located in the fibrillar layer outside the cell wall. A smaller amount of label was also found throughout the cytoplasmic area in the form of small clusters of gold particles, which suggests a macromolecular association. Mutant HB-7, which lacks the wall-associated AgC, accumulated AgC reactivity intracellularly. Intracellular AgC was often found associated with isolated areas of increased electron density, but sometimes seemed to fill the entire interior of the cell. Antigen B (AgB), a protein responsible for interbacterial coaggregation, was also located in the fibrillar layer, although its distribution differed from that of the wall-associated AgC since AgB was found predominantly in the peripheral areas. A very small amount of label was also found in the cytoplasmic area as discrete gold particles. Mutant HB-V5, which lacks wall-associated AgB, was not labeled in the fibrillar coat, but showed the same weak intracellular label as the parent strain. Immunolabeling with serum against AgD, another wall-associated protein but of unknown function, demonstrated its presence in the fibrillar layer of strain HB. Negatively stained preparations of whole cells of wild-type S. salivarius and mutants that had lost wall-associated AgB or AgC revealed that two classes of short fibrils are carried on the cell surface at the same time. AgB and AgC are probably located on separate classes of short, protease-sensitive fibrils 91 and 72 nm in length, respectively. A third class of only very sparsely distributed short fibrils (63 nm) was observed on mutant HB-V51, which lacks both wall-associated AgB and AgC antigens. The identity of these fibrils and whether they are present on the wild type are not clear. The function of long, protease-resistant fibrils of 178 nm, which are also present on the wild-type strain, remains unknown.

Adhesiveness↗
PubMedDate not supplied

Metastasectomy and active specific immunotherapy for a large single melanoma metastasis.

A patient with a large duodenal melanoma metastasis, involving adjacent jejunum and colon, is presented. Treatment consisted of a combination of radical surgery and active specific immunotherapy by means of an autologous tumor cell vaccine and BCG after which a recurrence-free survival of now more than 10 years has been observed. The role of surgery and immunotherapy in the treatment of metastatic melanoma are discussed.

Adenocarcinoma↗