Biomedical subjects

Gudrun Pohl

Publications and source records attributed to Gudrun Pohl.

15 recordsLinked to original sources

PubMed2006

"Laying on of hands" improves well-being in patients with advanced cancer.

GOAL OF WORK: To determine whether the impact of "laying on of hands" on the well-being of patients with advanced cancer is more efficient when performed by a person with self-declared "healing powers" as compared to an actor mimicking the healer in close detail. MATERIALS AND METHODS: A total of 80 patients were registered to participate in a randomized, single-blind phase III trial to evaluate the difference in efficacy of "laying on of hands" by either a "healer" or an actor. Each group consisted of 40 patients, scheduled to receive treatment for 5 min, three times a week. The effect of treatment was measured using a "Well-Being scale", with the difference of the average score of the "Well-Being scale" on day 10 being defined as primary and that on day 5 as secondary endpoint. MAIN RESULTS: There was no significant difference in average score values between the "healer" and the actor with regard to the primary (p = 0.34) or the secondary endpoint (p = 0.94), but the comparison was limited due to major protocol violations by the "healer" who unblinded his status after the first run and quit the study. The study was completed by the actor as a descriptive, explorative study on the impact of "laying on of hands". A significant improvement in symptoms after treatment was found on day 5 (p < 0.001) and on day 10 (p = 0.0002). CONCLUSION: "Laying on of hands" resulted in a significant improvement of cancer- or cancer-therapy-associated symptoms. The magnitude of improvement obtained was similar whether on a self-declared-healer- or an actor-provided "treatment".

Adult↗

PubMed2006

Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer.

Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol 175 mg/m2 over 3h on day 1, ifosfamide 1000 mg/m2 daily on days 1-3, cisplatin 60 mg/m2 on day 1, and prophylactic filgrastim 5 microg/kg daily on days 4-13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36-78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p=0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p=0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC.

Adult↗

PubMed2006

Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms.

Sequence mutations and gene amplifications lead to activation of the PIK3CA-AKT2 signaling pathway and have been reported in several types of neoplasms including ovarian cancer. Analysis of such genetic alterations, however, is usually complicated by contamination of normal cell DNA, artifacts associated with formalin-fixed tissues and the sensitivity of the techniques employed. In this study, we analyzed the sequence mutations in PIK3CA and AKT2 genes using purified tumor cells that were isolated from high-grade ovarian serous carcinomas and serous borderline tumors (SBTs) and assessed gene amplification using a dual-color FISH on tissue microarrays. Somatic sequence mutations in the kinase domain of AKT2 were not detected in any of the 65 ovarian tumors analyzed. Mutations of PIK3CA were rare, occurring only in one (2.3%) of 44 high-grade serous carcinomas and in only one (4.8%) of 21 SBTs. Dual-color FISH demonstrated that PIK3CA and AKT2 were not amplified in SBTs but amplified in 13.3% and 18.2% high-grade carcinomas, respectively. High-level amplification (>3 fold) was more frequently observed in AKT2 than in PIK3CA. Unlike mutations in ERBB2, KRAS and BRAF which are mutually exclusive in SBTs, coamplification of PIK3CA and AKT2 was present in five high-grade carcinomas including the OVCAR3 cells. Amplification in either of the genes occurred in 27% high-grade serous carcinomas. In conclusion, the methods we employed provide unambiguous evidence that somatic sequence mutations of PIK3CA and ATK2 are rare in ovarian serous tumors but amplification of both genes may play an important role in the development of high-grade ovarian serous carcinoma.

Carcinoma↗

PubMed2005

Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations.

Activation of mitogen-activated protein kinase (MAPK) occurs in response to various growth stimulating signals and as a result of activating mutations of the upstream regulators, KRAS and BRAF, which can be found in many types of human cancer. To investigate the roles of MAPK activation in tumors harboring KRAS or BRAF mutations, we inactivated MAPK in ovarian tumor cells using CI-1040, a compound that selectively inhibits MAPK kinase, an upstream regulator of MAPK and thus prevents MAPK activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated tumor cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. Long serial analysis of gene expression identified several differentially expressed genes in CI-1040-treated MPSC1 cells harboring an activating mutation in BRAF (V599L). The most striking changes were down-regulation of cyclin D1, COBRA1, and transglutaminase-2 and up-regulation of tumor necrosis factor-related apoptosis-induced ligand, thrombospondin-1, optineurin, and palladin. These patterns of gene expression were validated in other CI-1040-treated tumor cells based on quantitative PCR. Constitutive expression of cyclin D1 partially reversed the growth inhibitory effect of CI-1040 in MPSC1 cells. Our findings indicate that an activated MAPK pathway is critical in tumor growth and survival of ovarian tumors with KRAS or BRAF mutations and suggest that the CI-1040 induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian tumors.

Apoptosis↗

PubMed2005

Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE: The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer. PATIENTS AND METHODS: Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment. RESULTS: MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006). CONCLUSION: Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.

Adult↗

PubMed2005

Apolipoprotein E is required for cell proliferation and survival in ovarian cancer.

Apolipoprotein E (ApoE) has been recently identified as a potential tumor-associated marker in ovarian cancer by serial analysis of gene expression. ApoE has long been known to play a key role in lipid transport, and its specific isoforms may participate in atherosclerogenesis. However, its role in human cancer is not known. In this study, apoE expression was frequently detected in ovarian serous carcinomas, the most common and lethal type of ovarian cancer. It was not detected in serous borderline tumors and normal ovarian surface epithelium. Inhibition of apoE expression using an apoE-specific siRNA led to G(2) cell cycle arrest and apoptosis in an apoE-expressing ovarian cancer cell line, OVCAR3, but not in apoE-negative cell lines. Furthermore, the phenotype of apoE siRNA-treated OVCAR3 cells was reversed by expressing engineered mutant apoE with introduced silent mutations in the siRNA target sequence. Expression of apoE in nuclei was significantly associated with a better survival in patients who presented peritoneal effusion at the time of diagnosis (5-year follow-up, P = 0.004). This study suggests a new role of apoE in cancer as apoE expression is important for the proliferation and survival in apoE-expressing ovarian cancer cells.

Apolipoproteins E↗

PubMed2005

Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a gestational neoplasm derived from the extravillous (intermediate) trophoblast of the implantation site. PSTT is characterized by a highly invasive phenotype, but the molecular mechanisms are poorly understood. In this report, we demonstrate that PSTTs expressed the activated (phosphorylated) form of mitogen-activated protein kinase (MAPK) in 84% of cases, whereas the normal extravillous trophoblastic cells did not. To characterize the role of MAPK activation in PSTT, we established the first PSTT cell culture, IST-2, from a surgically resected PSTT. IST-2 cells expressed HLA-G and Mel-CAM but not E-cadherin, an immunophenotype characteristic of PSTT. IST-2 cells were highly motile and invasive in culture as compared to choriocarcinoma JEG-3 cells and normal extravillous trophoblastic cells. Based on wound assay, time-lapse videomicroscopy for cell tracking, and invasion chamber assays, we found that the motility and invasion of IST-2 cells were significantly reduced (P<0.01) after treatment with the MEK inhibitors CI-1040 and PD 59089, which prevent activation of MAPK. In contrast, neither compound had any effect on normal extravillous trophoblastic cells or JEG-3 cells. In conclusion, our findings demonstrate a functional role of MAPK activation in the motility and invasion of PSTT.

Benzamides↗

PubMed2004

Principle and applications of digital PCR.

Digital PCR represents an example of the power of PCR and provides unprecedented opportunities for molecular genetic analysis in cancer. The technique is to amplify a single DNA template from minimally diluted samples, therefore generating amplicons that are exclusively derived from one template and can be detected with different fluorophores or sequencing to discriminate different alleles (e.g., wild type vs. mutant or paternal vs. maternal alleles). Thus, digital PCR transforms the exponential, analog signals obtained from conventional PCR to linear, digital signals, allowing statistical analysis of the PCR product. Digital PCR has been applied in quantification of mutant alleles and detection of allelic imbalance in clinical specimens, providing a promising molecular diagnostic tool for cancer detection. The scope of this article is to review the principles of digital PCR and its practical applications in cancer research and in the molecular diagnosis of cancer.

Allelic Imbalance↗

PubMed2004

Anemia in multiple myeloma.

Anemia is a common complication in patients with multiple myeloma (MM) and occurs in more than two thirds of all patients. The most frequent underlying pathophysiological mechanism is anemia of chronic disease (ACD), relative erythropoietin (EPO) deficiency (due partly to renal impairment) and myelosuppressive effects of chemotherapy, but many other factors may account for or contribute to anemia in myeloma. In patients who achieve complete remission after chemotherapy, anemia usually normalizes. Nonresponders and relapsing myeloma patients often continue to suffer from anemia. Treatment options for anemic myeloma patients include red blood cell (RBC) transfusions and recombinant human erythropoietin (rHuEPO). Red blood cell transfusions convey an immediate effect and rapidly increase the patient's hemoglobin level. Unfortunately, effects of RBC transfusions are only transient and can be associated with several risks, including infections and mild to even life-threatening immunologic reactions. rHuEPO is biologically equivalent to the human endogenous hormone EPO, and its application leads to an increase of hemoglobin levels over an extended time without the risks of blood transfusions. Several studies reported a significant improvement of erythropoiesis, reduction in transfusion need, and improved quality of life by using rHuEPO as long-term treatment of myeloma-associated anemia. Recently, an international expert panel recommended the use of rHuEPO for anemic myeloma patients where other possible causes of anemia have been eliminated.

Anemia↗

PubMed2003

High p27Kip1 expression predicts superior relapse-free and overall survival for premenopausal women with early-stage breast cancer receiving adjuvant treatment with tamoxifen plus goserelin.

PURPOSE: To determine the predictive value of p27Kip1 in premenopausal women with early-stage hormone receptor-positive breast cancer. PATIENTS AND METHODS: We retrospectively examined tumor specimens from 512 patients with breast cancer who were enrolled onto Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5. In this trial, premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease were randomly assigned to receive either 5 years of tamoxifen plus 3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil. p27Kip1 expression was assessed by immunohistochemistry, and its association with clinical outcome was determined. Statistical analyses were performed to test for interaction between p27Kip1 status and treatment. RESULTS: High p27Kip1 expression (nuclear p27Kip1 staining in >/= 50% of tumor cells) independently predicted superior relapse-free survival (RFS) and overall survival (OS) in both the total study population (RFS: relative risk [RR], 0.53; 95% CI, 0.34 to 0.82; P =.004; OS: RR, 0.29; 95% CI, 0.15 to 0.58; P <.001) and patients treated with combination endocrine therapy (RFS: RR, 0.32; 95% CI, 0.16 to 0.63; P =.001; OS: RR, 0.16; 95% CI, 0.05 to 0.53; P =.003). The interaction between p27Kip1 expression and treatment was statistically significant for RFS (P =.04) but not for OS (P =.27). CONCLUSION: High p27Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor-positive breast cancer for adjuvant combination endocrine therapy.

Adult↗

PubMed2003

Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy.

Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p2lWaf1, p27KiP1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.

Adult↗

PubMed2003

Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with preoperative chemotherapy.

Our purpose was to determine the expression of the drug resistance factors multidrug resistance protein (MRP1), lung resistance protein (LRP) and P-glycoprotein (Pgp) in breast carcinoma patients treated with preoperative chemotherapy. We have studied the expression of these proteins in breast carcinomas by immunohistochemistry both prior (n = 80) and after (n = 68) preoperative chemotherapy and compared their expression with response to preoperative chemotherapy. In paired samples prior and after chemotherapy expression of drug resistance factors was significantly lower in prechemotherapy samples as compared with postchemotherapy specimens. This was observed for MRP1 (62% vs. 88%, P < 0.001), LRP (65% vs. 97%, P < 0.001) and Pgp (55% vs. 100%, P < 0.001). Prechemotherapy expression of MRP1 was more frequently observed in patients with distant metastases than in those without (50% vs. 8%, P = 0.02). No associations were observed between LRP expression and clinical parameters. Pgp expression was more frequently detected in lobular carcinomas than in ductal carcinomas (93% vs. 46%, P = 0.001) and in patients with positive lymph nodes than in patients with negative lymph nodes (65% vs. 31%, P = 0.008) but was independent of other clinical parameters. No significant associations were found between the prechemotherapy or postchemotherapy expression of either of these three proteins and response to preoperative chemotherapy. However, prechemotherapy MRP1 expression was significantly associated with shorter progression-free survival of the patients (P = 0.02), whereas no such associations were observed for either LRP or Pgp. In conclusion, preoperative chemotherapy increases the expression of MRP1, LRP and Pgp. Response to chemotherapy is not associated with pre- or postchemotherapy expression levels of these drug resistance proteins but time to progression may be influenced by prechemotherapy MRP1 expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Anemia in lung cancer: clinical impact and management.

Anemia has a high prevalence in patients with lung cancer. Its frequency and severity depend on tumor stage, duration of disease, and previous and current treatment. Anemia affects the health-related quality of life and impacts prognosis and outcome of therapy. Despite this clinical relevance, anemia is often underrecognized and undertreated. Treatment options include the administration of hematopoietic growth factors and red blood cell transfusions. Blood transfusions result in rapid but often transient improvement of anemia. Administration of epoetin or darbepoetin alfa increases hemoglobin levels, decreases blood transfusions, and improves quality of life in patients with lung cancer. Trials determining the exact association of anemia with response to chemotherapy/radiation therapy and survival are ongoing. Oncologists must be aware of the clinical relevance of anemia and offer adequate treatment options to their patients.

Anemia↗

PubMed2003

Low p27Kip1 expression is an independent adverse prognostic factor in patients with multiple myeloma.

PURPOSE: To determine the clinical relevance of p27(Kip1) in multiple myeloma (MM), we examined the relationship between p27(Kip1) expression at diagnosis and clinical as well as laboratory parameters, including response to chemotherapy and overall survival in 74 previously untreated patients with MM. EXPERIMENTAL DESIGN: Expression of p27(Kip1) was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded bone marrow biopsies. p27(Kip1) expression was classified as low (</=5% p27(Kip1)-positive myeloma cells) or high (>5% p27(Kip1)-positive myeloma cells). RESULTS: Low p27(Kip1) expression was observed in 23 (31%) patients. The response rate to standard dose chemotherapy (including vincristine, doxorubicin, and dexamethasone induction before high-dose chemotherapy) was 70%, with no significant difference between patients with low or high p27(Kip1) expression (83 versus 65%; P = 0.1). Kaplan-Meier analysis of all 74 patients revealed that patients with low p27(Kip1) expression had a significantly shorter overall survival (median, 3.7 years versus 4.7 years; P = 0.03) than those with high p27(Kip1) expression. Patients with high p27(Kip1) expression receiving high-dose chemotherapy experienced prolonged overall survival as compared with those with low p27(Kip1) expression (median not yet reached versus 2.9 years; P = 0.008). By multivariate Cox regression analyses, low p27(Kip1)(P = 0.03), deletion of chromosome 13q14 (P = 0.02), and beta(2)-microglobulin (P = 0.01) were identified as independent adverse prognostic factors for overall survival. According to the number of independent unfavorable prognostic factors present in each patient, low-risk, intermediate-risk, and high-risk patients with different overall survival times were defined (median overall survival, 6.3 versus 4.2 versus 1.8 years; P < 0.001). CONCLUSIONS: Low p27(Kip1) expression is an independent adverse prognostic factor in patients with MM. The proposed risk score might be useful for risk-adapted treatment in the future.

Adult↗

PubMed2002

Cyclin D3 is a predictive and prognostic factor in diffuse large B-cell lymphoma.

Cyclin D3 is an important regulator for transition from G(1) to the S phase of the cell cycle. Cyclin D3 expression is associated with cell proliferation in lymphoid tissues, but its impact on clinical outcome in non-Hodgkin's lymphomas has not been studied. Therefore, we determined the clinical relevance of cyclin D3 expression in patients with diffuse large B-cell lymphoma. We examined the relation between cyclin D3 expression at diagnosis and response to conventional polychemotherapy and overall survival in 81 previously untreated patients with diffuse large B-cell lymphoma. Cyclin D3 expression was assessed by immunohistochemistry. Cyclin D3 immunostaining ranged from 0-100% (median, 30%) of the lymphoma cells. Patients with high (>or=50% cyclin D3-positive lymphoma cells) cyclin D3 expression had a more advanced clinical stage (P = 0.003) and more often had extranodal disease in more than one site (P = 0.007) than patients with low cyclin D3 expression. Patients with high cyclin D3 expression had a significantly lower complete response rate (17% versus 74%; P < 0.001) and a shorter overall survival (3-year survival rate, 18% versus 74%; P < 0.001) than those with low cyclin D3 expression. Multivariate analyses that included cyclin D3 and the International Prognostic Index demonstrated that cyclin D3 expression had independent effects on the complete response rates and overall survival of the patients. In conclusion, high cyclin D3 expression is an independent predictive and prognostic factor associated with poor clinical outcome in patients with diffuse large B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗