Biomedical subjects

T Bachleitner-Hofmann

Publications and source records attributed to T Bachleitner-Hofmann.

9 recordsLinked to original sources

PubMed2004

High nuclear grade and negative estrogen receptor are significant risk factors for recurrence in DCIS.

INTRODUCTION: Recommendations for adjuvant treatment of DCIS after breast conservation are controversial. We tried to identify further risk factors in a retrospective study of our own practice. PATIENTS AND METHODS: Three hundred and thirty-two patients treated by breast conservation between 1978 and 2001 at the Department of General Surgery, University of Vienna were analysed. Tumour size, nuclear grade, hormone receptors, p53, her-2/neu, multifocality, microinvasion and post-operative therapy (irradiation, tamoxifen or combination) were analysed for their influence on breast recurrence. RESULTS: Overall recurrence rate was 6.1% (8/132). For patients with DCIS showing high nuclear grade or negative estrogen receptor the risk for development of ipsilateral breast recurrence is significantly higher. Newer factors like p53 and her-2/neu do not have any prognostic significance. No recurrence was observed in patients treated by post-operative irradiation and tamoxifen. CONCLUSION: Nuclear grade remains the most significant factor for breast recurrence after DCIS. Hormone receptor status identifies a subset of patients with more favourable prognosis.

Adult↗

PubMed2003

Dendritic cell-based vaccination in solid cancer.

PURPOSE: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs. PATIENTS AND METHODS: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses. CONCLUSION: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.

Adult↗

PubMed2002

Arsenic trioxide: acute promyelocytic leukemia and beyond.

Arsenic containing treatments have a history of over two millenniums. Recently, arsenic trioxide (As2O3) has been introduced into the treatment of both de now and relapsed acute promyelocytic leukemia (APL), with remarkable clinical success. Several investigations using both freshly isolated APL blast cells as well as APL-derived tumor cell lines have shown that the main mechanism by which As2O3 exerts its antileukemic activity in APL is induction of apoptosis in the leukemic cell population. Recently, it has become evident that the apoptotic effects of As2O3 are not restricted to APL cells but may also be observed in malignant cells of non-APL origin. In the present review, history, current clinical use as well as future perspectives of As2O3 therapy in both hematologic and solid malignancies are discussed, with special emphasis being put on the potential future role of As2O3 in the treatment of non-APL tumors. Of particular importance, enhancing agents suited to increase As2O3-sensitivity in less sensitive tumors (e.g. ascorbic acid) are also addressed.

Angiogenesis Inhibitors↗

PubMed2002

Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells.

Dendritic cells (DCs) have attracted wide interest because of their unique capacity to elicit primary and secondary antitumor responses. We have generated autologous tumor lysate-pulsed DCs from three patients with medullary thyroid carcinoma (MTC) and tested them for their ability to stimulate cytotoxic T-cell responses against autologous MTC tumor cells in vitro. The aim of our investigations was to evaluate the potential efficacy of DC-based immunotherapy in patients with MTC. DCs were generated from peripheral blood monocytes using GM-CSF and IL-4 (immature DCs) or GM-CSF, IL-4, and TNFalpha (mature DCs). Our results indicate that mature tumor lysate-pulsed DCs are able to elicit a human leukocyte antigen class I-restricted cytotoxic T-cell response against autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do not stimulate significant antitumor activity. We feel that our data may be relevant for future clinical trials of active immunotherapy using tumor lysate-pulsed DCs in patients with MTC who have residual or distant disease after surgical treatment. The fact that mature DCs displayed a substantially higher capacity to stimulate autologous antitumor T-cell responses than immature DCs underlines the importance of a maturation step in immunotherapy protocols based on DCs.

Adult↗

PubMed2001

Arsenic trioxide and ascorbic acid: synergy with potential implications for the treatment of acute myeloid leukaemia?

Arsenic trioxide (As2O3) induces remission in a high proportion of patients with acute promyelocytic leukaemia (APL) via induction of apoptosis. Preliminary reports suggest that the apoptotic effect of As2O3 is not specific for APL but can also be observed in non-APL acute myeloid leukaemia (AML) cells, although these are less sensitive than APL cells. Ascorbic acid has recently been demonstrated to enhance the apoptotic effect of As2O3. We have therefore evaluated combined As2O3/ascorbic acid treatment in various clinical samples of AML. Our results indicate a significant synergistic effect of As2O3 and ascorbic acid, suggesting a possible future role of As2O3/ascorbic acid combination therapy in patients with AML.

Acute Disease↗

PubMed2000

[Surgical axilla dissection. Technical standard or obsolete method?].

Axillary lymph node status remains the single most important prognostic parameter and has crucial therapeutic implications in patients with breast carcinoma. Surgical dissection of the axilla is commonly regarded as the standard procedure of axillary staging, its sensitivity and specificity being 99% and 100%, respectively. Apart from giving reliable information on the individual prognosis axillary dissection also contributes to efficient local tumor control in the axilla, as it reduces the risk of local recurrence to less than 1.4% if more than 10 lymph nodes are removed. Alternative, less or non-invasive axillary staging methods have either not yet been sufficiently standardized (immunoscintigraphy, PET-scan, prediction of axillary lymph node status by means of individual risk factors) or are associated with a considerable risk of false-negative staging (up to 50% of patients with positive axillary lymph nodes are not detected by palpation alone, ultrasonography or CT-scan). The basic principles of axillary sampling and axilloscopic dissection are questionable because the number of lymph nodes removed during these procedures is commonly less than 10. With its sensitivity/specificity being comparable to that of standard axillary dissection sentinel lymph node biopsy represents a highly promising approach which will in the future potentially lead to significant optimization of the clinical management of patients with breast cancer, especially those diagnosed in early stages (T1 a, T1 b and T1 c).

Axilla↗

PubMed1999

The role of interferon-alpha in the treatment of idiopathic myelofibrosis.

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow, varying degrees of extramedullary hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic peripheral blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and calmodulin. Because of the variable clinical course of IMF, attempts have been made to define prognostic parameters that can be helpful in detecting patients with a shortened life expectancy. The most important adverse prognostic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. However, no standardized prognostic score for IMF has yet been established. Therapeutic strategies in IMF remain predominantly supportive. The most common are blood transfusions, androgens, and cytoreductive agents such as hydroxyurea. Bone marrow transplantation is increasingly being taken into consideration, but it still has to be regarded as an experimental approach. Interferon-alpha (IFN-alpha) has shown promising results in early hyperproliferative stages of IMF but has no or only very little effect in more advanced stages of the disease. Whether IFN-alpha is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials.

Humans↗

PubMedDate not supplied

Heat treatment of hepatocellular carcinoma cells: increased levels of heat shock proteins 70 and 90 correlate with cellular necrosis.

Immunotherapy, i.e. stimulation of the body's immune response against tumor cells, is a promising approach in cancer treatment. In this context, heat shock proteins (HSP) have been shown to function in tumor antigen chaperoning. HSP are evolutionarily conserved and show increased expression in response to chemical and physical stress. Two members of the HSP family, HSP 70 and 90, seem to further act as immunostimulating agents because of their possible involvement in tumor antigen presentation. We cultured the human hepatocellular carcinoma cell line HepG2 and investigated its HSP content under normal and hyperthermic conditions. Flow cytometry showed increased levels of HSP 70 and 90 after heat shock at 41.8 degrees C for 60 minutes, measured after a subsequent incubation time of five hours, as compared to untreated cells in vitro. We further observed a clear correlation between the HSP 70 and 90 levels and the necrotic cell subpopulation in heat shocked tumor cells. We conclude that HSP expression in HepG2 cells can be enhanced by heat shock treatment in vitro. We suggest that this mechanism can be exploited in increasing tumor immunogenicity.

Antibodies, Monoclonal↗

PubMedDate not supplied

Marked and sustained improvement of systemic sclerosis following polychemotherapy for coexistent multiple myeloma.

We present the case of a patient who had systemic sclerosis (SSc) with progressive cutaneous and pulmonary involvement and a coexisting monoclonal gammopathy which gradually progressed to overt multiple myeloma. Strikingly, successful VMCP (vincristine, melphalan, cyclophosphamide and prednisolone) polychemotherapy for myeloma was accompanied by a marked and sustained improvement of SSc that has persisted for 2 years after chemotherapy. Most noticeable was a substantial skin softening in our patient, with a > 50% reduction in the skin thickness score following VMCP treatment. Our case suggests that polychemotherapy may represent a promising treatment option in patients with SSc who are refractory to available treatments.

Aged↗