Biomedical subjects

Verena Voelter

Publications and source records attributed to Verena Voelter.

7 recordsLinked to original sources

PubMed2006

New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site.

Although increasing evidence suggests that CTL are important to fight the development of some cancers, the frequency of detectable tumor-specific T cells is low in cancer patients, and these cells have generally poor functional capacities, compared with virus-specific CD8(+) T cells. The generation with a vaccine of potent CTL responses against tumor Ags therefore remains a major challenge. In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags. Nonetheless, the eventual impact on tumor development in vaccinated melanoma donors remained limited. The comprehensive study of vaccinated patient metastasis shows that vaccine-driven tumor-infiltrating lymphocytes, although activated, still differed in functional capacities compared with blood counterparts. This coincided with a significant increase of FoxP3(+) regulatory T cell activity within the tumor. The consistent induction of effective tumor-specific CD8(+) T cells in the circulation with a vaccine represents a major achievement; however, clinical benefit may not be achieved unless the tumor environment can be altered to enable CD8(+) T cell efficacy.

Adult↗

PubMed2006

Ex vivo detectable human CD8 T-cell responses to cancer-testis antigens.

Clinical trials have shown that strong tumor antigen-specific CD8 T-cell responses are difficult to induce but can be achieved for T-cells specific for melanoma differentiation antigens, upon repetitive vaccination with stable emulsions prepared with synthetic peptides and incomplete Freund's adjuvant. Here, we show in four melanoma patients that ex vivo detectable T-cells and thus strong T-cell responses can also be induced against the more universal cancer-testis antigens NY-ESO-1 and Mage-A10. Interestingly, all patients had ex vivo detectable T-cell responses against multiple antigens after serial vaccinations with three peptides emulsified in incomplete Freund's adjuvant. Antigen-specific T-cells displayed an activated phenotype and secreted IFNgamma. The robust immune responses provide a solid basis for further development of human T-cell vaccination.

Antigens, Neoplasm↗

PubMed2006

Erythropoietin-alfa during neoadjuvant chemotherapy for locally advanced esophagogastric adenocarcinoma.

BACKGROUND: In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy. METHODS: Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications. RESULTS: Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events. CONCLUSIONS: Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Adenocarcinoma↗

PubMed2005

Immuno-monitoring of CD8+ T cells in whole blood versus PBMC samples.

The study of natural T cell responses against pathogens or tumors, as well as the assessment of new immunotherapy strategies aimed at boosting these responses, requires increasingly precise ex vivo analysis of blood samples. For practical reasons, studies are often performed using purified PBMC samples, usually cryopreserved. Here, we report on FACS analyses of peripheral blood T cells, performed by direct antibody staining of non-purified total blood. For comparison, fresh PBMC, purified by Ficoll, were analysed. Our results show that the latter method can induce a bias in subpopulation distribution, in particular of CD8+ T cells, and sometimes lead to inaccurate measurement of antigen specific CD8+ T cell responses. Direct analysis of total blood can be applied to longitudinal immuno-monitoring of T cell-based therapy. While the need to purify and cryopreserve PBMC for subsequent studies is obvious, the use of whole blood has the advantage of providing unbiased results and only small amounts of blood are used.

Blood Cells↗

PubMed2005

[Breaking bad news].

Breaking bad news is one of the most stressful duties of the physician in oncology. Among other issues, it includes discussion of cancer diagnosis or the failure of therapy. The oncologist is often puzzled by an apprehension regarding the delivery of bad news. The fear to be exposed to unexpected strong emotional reactions by the patient, such as aggression or despair, may cause the oncologist to adopt unproductive coping strategies such as discussion about technical details while avoiding to deliver the main message. However, good communication skills are the key for a satisfying conversation with the patient. The oncologists' discomfort induced by the above mentioned apprehension is one of the most important barriers for a successful conversation.

Communication↗

PubMed2004

Incidence of anemia in patients receiving neoadjuvant chemotherapy for locally advanced esophagogastric cancer.

BACKGROUND: There is rising evidence that anemia and blood transfusion increase perioperative mortality in cancer patients. Patients who are treated with neoadjuvant chemotherapy with a curative intent are exposed to toxicity that may negatively affect their future outcome. METHODS: The charts of 29 patients (21 males; median age, 59.5 years; range, 37 to 73), receiving neoadjuvant chemotherapy for cT3 esophagogastric adenocarcinoma operated at a single university center in the year 2002, were retrospectively reviewed to assess the incidence of anemia and blood transfusions. RESULTS: Twenty-six patients received platinum-based chemotherapy over a period of 12 weeks and three patients more than 6 weeks. The median hemoglobin level (Hb level) before chemotherapy was 14.0 g/dL (range, 10.4 to 15.9 g/dL), the median decline of the Hb level was 2.9 g/dL (range, 0.3 to 6.3 g/dL); this drop was statistically significant (p < 0.001, 95% confidence interval). Patients who received preoperative blood transfusions (n = 8, 28%) had a significantly increased risk of developing postoperative complications (p = 0.028). CONCLUSIONS: Preoperative chemotherapy for locally advanced esophagogastric cancer induces anemia and therefore leads to preoperative blood supplementation in a considerable number of patients. Data indicate that this may counteract the beneficial effects of neoadjuvant treatment.

Adenocarcinoma↗

PubMed2003

Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study.

PURPOSE: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. METHODS AND MATERIALS: Twenty-eight patients (19 males; median age 63, range 28-75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN+: 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30-105 mg/m(2)/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid x 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. RESULTS: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m(2)). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. CONCLUSIONS: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m(2)/week. Further Phase II exploration at this dose is warranted.

Adolescent↗