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Biomedical subjects

K Possinger

Publications and source records attributed to K Possinger.

At least 145 records · Page 8Linked to original sources
PubMed1980

[In vitro resistance testing of tumors in relation to cytostatics. 2. Examinations with human malignomas].

The in vitro test presented here can be used to demonstrate chemotherapy drug (CD) resistance in human tumors showing high metabolic activity. Initially, dose-effect ratios are determined for various CDs in patients showing in vivo CD resistance (primary or secondary) and correlated with the inhibition of incorporation rates for radiolabeled DNA and RNA precursors in tumor cells. The maximal incorporation inhibition noted was 28% for the highest CD concentration used, and 17% for one tenth of that concentration, compared to controls. Accordingly, those tumor cells were termed "resistant" which showed a maximal incorporation inhibition of 28 and 17%, respectively, under the highest CD concentration used for the test. A total of 94 human tumors were tested, and the patient's response to CDs was evaluated after 12 weeks of therapy. In 57 of them, the in vitro test correctly predicted CD resistance as confirmed by the clinical course. There was no resistance demonstrated in vitro in another 13 cases which actually showed progression of disease while receiving CDs. In 24 cases there was good agreement between lack of resistance in vitro and clinical response.

Adenocarcinoma↗
PubMed1979

[Influence of hydroxyurea on DNA synthesis of human bone marrow in vivo (author's transl)].

Four patients, who suffered from malignant, disseminated tumors but had a morphologically intact bone marrow, where given a peroral Hydroxyurea (HU) infusion in a concentration of about 5 x 10(-4) mol over a period of 10 h. As indicator of the DNA synthesis the 3H-TdR-incorporation of bone marrow, gained by puncture before, during, and/or after HU application, was measured. While using HU, the DNA synthesis was extensively inhibited. Fourteen to 16 h after discontinuing the HU it increased by the factor 1.5 to 2 of the initial value, i.e., before treatment. This is interpreted as a partial synchronization of bone marrow cells where effects of cell depletion and recruitment are not to be entirely excluded, Toxicity, such as the decrease of peripheral blood cells or nausea, did not occur.

Adult↗
PubMed1977

[Partial synchronization of tumor cells in vivo with hydroxyurea (author's transl)].

For the partial synchronization of tumor cells, Yoshida ascitic sarcoma bearing rats were treated with Hydroxyurea using two methods, one in the form of a single intraperitoneal injection (0.5 mg/g body weight) and the other by continuous intraascitic infusion over a period of 12h (1.428 mg/g body weight total dose). The synchronization obtained by continuous infusion of Hydroxyurea is superior to that by a one time injection with respect to cell accumulation in one phase of the cell cycle and in the duration of synchronous proliferation. The degree of cell loss caused by infusion depends on the concentration of Hydroxyurea. Concentrations of slightly more than the minimal inhibitory concentration of DNA synthesis cause the least damage to the tumor cells.

Animals↗
PubMed1976

[Resistance testing of cytostatic agents on human tumors (author's transl)].

An in vitro short term incubation of human tumors with different cytostatic agents and their corresponding radioactive precursors of cell metabolism allows detection of those drugs which are inefficacious on the examined tumor. The pretherapeutical knowledge of those substances keeps the patient from unnecessary and damaging cytotoxic treatment. The in vitro and in vivo correlation of this technique was tested on 3 different groups of tumor patients: 1. Chemotherapeutically treated tumor patients with primary or secondary induced resistance against the applied cytostatic agents: all substances which clinically did not influence the tumor growth at the moment of the test also were inefficient in the in vitro test system. 2. Tumor patients who were treated according to a clinical therapy regimen contrary to the results of the in vitro testing: corresponding to the test, no influence on tumor growth was seen. 3. Tumor patients who were treated according to the results of the resistance test: after 8 weeks observation none of these patients had any signs of tumor progression.

Antineoplastic Agents↗
PubMedDate not supplied

Preliminary study on administration of high-titer lipid A antibody serum in sepsis and septic shock patients.

To determine whether sera containing high titers of lipid A antibody may be applicable at effective doses in treating patients with septicemia, a pharmacokinetic study was performed in seven patients aged 24 to 73 years with gram-negative septicemia and various underlying diseases, one of whom received a placebo, and in one patient without infection. In this study, we attempted to determine the effective dosage, the number of infusions and appropriate administration interval for the prevention and treatment of endotoxin shock. Blood samples from each patient were tested for lipid A antibodies before and at regular intervals after administration using an enzyme-linked immunosorbent assay (ELISA). Selected, pooled human immunoglobulin preparations containing high titers (expressed as exponents of 10) of IgG (titer = 3-4) and IgM (titer = 2-4) lipid A antibodies were administered first at a dosage of 8 ml/kg body weight. After administration, the mean lipid A antibody titer increased from 0.4 to 2.3 for IgG and from 2 to 2.4 for IgM. The initial increase was followed by a drop in titer within 24 h, which was perhaps due to antibody consumption. Following the second administration (24 h after the first) of only 4 ml/kg body weight, the mean IgG and IgM titers increased to 2.4 and 3.3, respectively, and dropped slower. A notable increase in circulating lipid A antibody titers was achieved, and four of six treated patients recovered from the sepsis. The two patients who died entered the study in a pre-terminal state. These studies encouraged us to initiate a randomized, double-blind controlled study.

Adult↗
PubMedDate not supplied

Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis.

An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.

Absidia↗
PubMedDate not supplied

Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer predicting the response to second-line hormone or chemotherapy.

Concentrations of soluble c-erbB-2 were determined in the sera of 64 patients with distant metastasis from advanced breast cancer receiving second-line hormone or chemotherapy in comparison to 35 breast cancer patients without detectable recurrent disease and 17 healthy blood donors. The sera of non-metastatic breast cancer patients contained s-erbB-2 concentrations similar to those of healthy blood donors. Patients with distant metastasis from advanced breast cancer had significantly higher values of s-erbB-2 in comparison to patients with non-disseminated disease (mean: 59.6 vs. 11.6 U/ml; p = 0.022). A significant correlation was observed between s-erbB-2 serum levels and serum LDH concentrations (p < 0.001), levels of alkaline phosphatase (p < 0.001), and the presence of hepatic metastasis (p = 0.001). Time to tumor progression was significantly shorter in patients with s-erbB-2 levels above 40 U/ml (mean: 23.4 vs. 56.7 months; p = 0.002). Furthermore, breast cancer patients with hepatic metastasis and those with elevated s-erbB-2 serum levels above 40 U/ml had limited response to hormone or chemotherapy. Non-responders had significantly higher s-erbB-2 levels (mean: 270.3, range: 42-500 U/ml;) compared with the responder group (mean: 23.1, range: 0-149 U/ml; p < 0.001). Logistic regression analysis indicated that elevated s-erbB-2 serum levels above 40 U/ml independently predicted an unfavorable response to second-line hormone or chemotherapy in patients with advanced metastatic breast cancer.

Adult↗
PubMedDate not supplied

Biomarkers and imaging in non-malignant and malignant osteomalacia.

Deoxypyridinium (DPD) cross-links are a specific parameter for collagen type I degradation. We report the longitudinal tracking of DPD in relation to other bone markers and imaging techniques in a patient with osteomalacia and secondary hyperparathyroidism from reduced light exposure due to attire. This patient was first admitted for diffuse skeletal pain. X-rays showed general demineralization and Looser's transformation zones in the neck of the left femur. MRI examinations of the pelvis and the proximal femora demonstrated bilateral signs of acute sacroiliitis, as well as edema-like lesions in the femoral heads and necks bilaterally. The baseline parathyroid hormone level was 8 times higher than the normal upper limit, whereas 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly reduced. A 7-fold increase in free urinary DPD and a 17-fold increase in bone-specific alkaline phosphatase (bone-AP) were also measured. Percutaneous transiliac bone biopsy revealed markedly increased osteoidosis. Osteomalacia was diagnosed due to chronically reduced sun exposure caused by restrictive attire, and cholecalciferol substitution therapy was begun. After a follow-up of 28 weeks, non-specific parameters of bone turnover (parathyroid hormone, total alkaline phosphatase, serum calcium and serum phosphate) had normalized, while DPD, as a specific bone degradation marker, and bone-AP, as a bone formation parameter, both remained elevated. This example underlines the validity of DPD and bone-AP as indicators of increased bone metabolism: not only were they the parameters with the highest baseline deviation, but they were also the last to normalize.

Adolescent↗
PubMedDate not supplied

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of healthy adults.

AIMS: Osteoprotegerin and the receptor activator of the nuclear factor-kappaB ligand (RANKL) are decisive factors for maintaining the balance between bone formation and bone resorption. As new, sensitive ELISAs have been developed recently, reference serum ranges should be established to use these analytes for possible diagnostic purposes. METHODS: Measurements were performed in serum samples of 142 healthy adults (82 women, 60 men) between 20 and 70 years of age (mean age: 46 years) using ELISA kits from Immundiagnostik, Bensheim, Germany. RESULTS: Serum concentrations of osteoprotegerin were age and gender independent and showed a Gaussian distribution, while RANKL concentrations were also age independent but differed between males and females, with a non-Gaussian distribution. For osteoprotegerin a gender-independent upper 97.5 percentile limit of 3.6 pmol/L was calculated while the corresponding limits for RANKL and the ratio of RANKL to osteoprotegerin amounted to 3.29 pmol/L and 2.78 in women and 1.66 pmol/L and 2.18 in men, respectively. CONCLUSIONS: Both osteoprotegerin and RANKL were quantifiable in serum of healthy adults, which means that these compounds can be used as potential diagnostic tools.

Adult↗
PubMedDate not supplied

Discordant results obtained for different methods of HER-2/neu testing in breast cancer--a question of standardization, automation and timing.

BACKGROUND: HER-2/neu positivity is required for the selection of stage IV breast cancer patients for trastuzumab therapy. We compared the results of the recommended immunohistochemistry (IHC) evaluation with the automated ACIS IHC system and with fluorescence in situ hybridization (FISH). These HER-2/neu tissue results were correlated with the serum HER-2/neu (sHER-2/neu) levels at the time of metastatic spread. PATIENTS AND METHODS: A total of 61 IHC slides from 30 patients were stained using the HercepTest. HER-2/neu gene amplification was determined using the Ventana FISH assay. sHER-2/neu levels were measured with the Oncogene Science" ELISA kit. The concordance of HER-2/neu results was determined using the concordance index Kappa (kappa). RESULTS: The best concordance between any IHC and FISH was found for the automated ACIS system (88.5%, kappa=0.68, category "good"). The comparison between the manual interpretations and the automated IHC was categorized as "very good" (95.1%, kappa=0.85). The median sHER-2/neu level of FISH positive patients was significantly higher (67 ng/mL) than that of FISH negative patients (17 ng/mL, p=0.018). The increase in HER-2/neu positivity comparing tissue to stage IV serum was statistically significant (p=0.001). CONCLUSIONS: The concordance between conventional IHC and computerized analysis was very good. The number of patients with stage IV breast cancer with an elevated sHER-2/neu level was much higher than HER-2/neu positivity in tissue. This discrepancy is only partially explained by the influence of tumor load. Patients with an elevated sHER-2/neu level and no tissue overexpression should be considered for retesting of tissue or a new biopsy.

Biomarkers, Tumor↗
PubMedDate not supplied

ADVIA Centaur HER-2/neu shows value in monitoring patients with metastatic breast cancer.

INTRODUCTION: The proteolytic breakdown product corresponding to the extracellular domain (ECD) of the HER-2/neu oncoprotein p185 is found in the circulation of healthy individuals and patients having cancers of epithelial origin. For the current evaluation we sought to determine the analytical performance as well as the clinical utility of the newly developed ADVIA Centaur HER-2/neu assay (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY, USA) in monitoring patients with metastatic breast cancer during the course of disease and treatment and to compare the obtained results with those of CA 15-3. METHODS: The analytical performance (including precision, normal range, interfering substances, minimum detectable concentration, dilution recovery, spiking recovery and high-dose hook effect) were determined. HER-2/neu and CA 15-3 values were measured in retrospective samples obtained from 59 patients with metastatic breast cancer undergoing treatment over a 6-12 month period. Serial changes in serum HER-2/neu and CA 15-3 were correlated with changes in clinical status on a visit-to-visit basis. For each pair of serial measurements, changes of equal to or greater than, or less than 15% for HER-2/neu and 21% for CA 15-3 were considered to indicate progression or lack of progression, respectively. RESULTS: The ADVIA Centaur HER-2/neu assay demonstrated within-run imprecision and total imprecision ranging from 3.0-5.6% and from 3.2-5.7%, respectively. The upper limit of normal was 15.2 ng/mL (90% CI: 14.2-17.0 ng/mL). No significant interference (<5%) was seen with bilirubins, hemoglobin, triglycerides and cholesterol or therapeutic drugs commonly present in the sera of breast cancer patients. The minimum detectable concentration (analytical sensitivity) was found to be 0.5 ng/mL. The patient population in the clinical study included breast cancer patients who responded to therapy (stable, partial or complete response) or had disease progression. HER-2/neu levels showed a concordance of 78.1% (82/105 restaging time points) with the clinical course of disease, whereas CA 15-3 levels showed a concordance of 76.2% (80/105 restaging time points). The concordance with clinical status increased to 85.7% (90/105 restaging time points) when both results were used in combination as a series test. CONCLUSIONS: The ADVIA Centaur HER-2/neu assay provides excellent analytical performance for serial testing of serum HER-2/neu levels. The clinical data demonstrate the usefulness of serum HER-2/neu in monitoring metastatic breast cancer patients during treatment. Furthermore, the results indicate that serum HER-2/neu and CA 15-3 may be useful in identifying disease progression or therapeutic response in different subgroups of women with metastatic breast cancer.

Adult↗
PubMedDate not supplied

c-erbB-2 in serum of patients receiving fractionated paclitaxel chemotherapy.

Humanized anti-c-erbB-2 antibodies (Herceptin) in a weekly schedule are a new therapeutic option for the treatment of c-erbB-2-positive, advanced breast cancer (ABC). Addition of Herceptin to first-line chemotherapy for c-erbB-2 overexpressing ABC increased anticancer activity in a randomized phase III trial. However, except from standard UICC response criteria, there are hitherto no recommendations as to how to monitor Herceptin therapy. In a therapy optimizing study with weekly dose-intensified paclitaxel monotherapy (schedule: 90 mg/m2 weekly x 6, q9w), we correlated the clinical course of stage IV breast cancer in UICC criteria with the course of the shed c-erbB-2 protein fragment and the CA 27.29 serum level. Serum samples were taken weekly from 35 patients to measure the serum c-erbB-2 and CA 27.29 protein levels over time. Up to now, 10 patients (28.5%) are c-erbB-2 positive (> 15 U/mL), with a median baseline protein expression of 65 U/mL. While the overall response rate in the study is 36%, the response rate among c-erbB-2-positive patients is 62%, indicating a high sensitivity of c-erbB-2 positive patients to dose-intense paclitaxel treatment. In all responders the c-erbB-2 serum level decreased below the detection limit either before the clinical diagnosis of response or by the end of the next cycle. However, the normalization of the c-erbB-2 serum level was not specific for responders as patients with stable or progressive disease presented normalized levels or a > 50% decrease of the baseline level, too. The courses of the c-erbB-2 protein levels correlated closely with the courses of CA 27.29. The decrease in the serum c-erbB-2 oncoprotein level might indicate a regression of c-erbB-2 positive tumor load. This may even happen in progressive disease according to UICC criteria when the c-erbB-2-negative tumor fraction progresses while the c-erbB-2-positive fraction is controlled. Another explanation would be that the mechanisms of c-erbB-2 shedding change under chemotherapy, with less of the c-erbB-2 protein fragment being released to the serum, which would make the c-erbB-2 positive tumor cells a better target for anti-c-erbB-2 antibody treatment.

Antigens, Tumor-Associated, Carbohydrate↗
PubMedDate not supplied

The course of the urinary DPD-crosslink secretion in metastatic breast cancer--a possibility for response assessment.

BACKGROUND: Urinary deoxypyridinoline (DPD)-crosslinks have been shown to be a highly specific parameter for type I collagen metabolism. MATERIALS AND METHODS: In a prospective breast cancer study, urine samples were collected in after-care patients and in patients with bone metastases. DPD-crosslinks were measured every three weeks using a fully automated chemiluminescence immunoassay. Bone metastases were confirmed by bone scan and/or x-ray, and were followed-up over six months. To validate the test, a receiver operating characteristics (ROC)-curve was set up to find the DPD cut-off concentration which separates patients with no evidence of disease (NED) from patients with bone metastases. RESULTS: 73 breast cancer patients (41 with NED, 32 with bone metastases) were included into the ROC analysis. At a DPD cut-off value of 8 nmol/mmol creatinine, we found the best sensitivity (84.4%) for the detection of bone metastases with a specificity of 70.7%. Patients with stable bone disease under intravenous pamidronate treatment (90 mg q3w) and specific therapy had a significant (p = 0.007) fall of the DPD-crosslinks in comparison to the progressive subset with 72.7% falling below 8 nmol/mmol. CONCLUSIONS: We conclude that the net bone turnover is not increased at a DPD-crosslinks elimination < 8 nmol/mmol.

Adult↗
PubMedDate not supplied

Adjuvant high-dose chemotherapy with epirubicin and ifosfamide in nodal positive breast cancer.

INTRODUCTION: Morbidity and mortality, disease-free- and overall survival were analysed in an adjuvant high-dose chemotherapy (HDCT) study with ifosfamide and epirubicin for high-risk (> or = 10 positive lymph nodes) breast cancer. PATIENTS AND METHODS: A total of 21 patients (pts) were treated with 4 cycles of ViEC (vindesine, epirubicin, cyclophosphamide) as standard chemotherapy. After the second cycle, CD34+ stem cells were mobilised with G-CSF. HDCT consisted of epirubicin 100 mg/m2 on days (-5)-(-4) before stem-cell rescue and ifosfamide 5000 mg/m2 on days (-5)-(-2). RESULTS: No therapy-related deaths occurred. Mucositis WHO grade III/IV in 52% and neutropenic fever in 81% were the most relevant toxicities. Nausea and vomiting WHO grades III/IV were found in 62.2%. The median duration of leucopenia grade IV was 7 days (range: 4-11) with a median time to platelet recovery > 50,000/microliter of 6 days (range: 4-11). After a median follow-up time of 21 months (range: 12-49 months), six of 21 pts (28.6%) relapsed. Two patients died 12 and 18 months after initial diagnosis. CONCLUSIONS: Adjuvant HDCT with epirubicin and ifosfamide is safe and shows good tolerability for high-risk breast cancer.

Adult↗
PubMedDate not supplied

Tumor type M2 pyruvate kinase expression in advanced breast cancer.

BACKGROUND: Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls. MATERIALS AND METHODS: Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA). RESULTS: In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly. CONCLUSION: Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.

Adult↗
PubMedDate not supplied

A comparison of bone-related biomarkers and CA27.29 to assess response to treatment of osseous metastatic breast cancer.

BACKGROUND: The assessment of bone metastases by clinical examination or imaging techniques is still considered unreliable. We compared a specific marker of bone resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca), alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases in patients with breast cancer. MATERIALS AND METHODS: Second morning voided urine was collected from 2 groups of patient (pts), those without evidence of disease (n = 118), and those with bone metastases (n = 85) under specific therapy plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC) curves were established for each of the 4 biomarkers to determine whether they could distinguish the 2 subsets of pts with clinically sufficient validity, and to establish the corresponding cut-off values. RESULTS: Neither Ca nor AP was useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we found a specificity of 69% and a sensitivity of 53% for diagnosing bone metastases. Best results, however, were seen for CA27.29. A cut-off value of 30 U/ml resulted in a specificity of 62% and a sensitivity of 81%. CONCLUSIONS: CA27.29 was the best parameter for the discrimination of stage IV breast cancer with bone metastases. The primary advantage of DPD lies in the monitoring of bone metastases under specific therapy.

Adult↗
PubMedDate not supplied

Predictive relevance of soluble CD44v6 serum levels for the responsiveness to second line hormone- or chemotherapy in patients with metastatic breast cancer.

Concentrations of soluble CD44 standard (sCD44std) and CD44 variant 6 (sCD44v6) isoforms were determined in the sera of 59 patients with distant metastasis from breast cancer receiving second line hormone- or chemotherapy, in comparison to 46 breast cancer patients without detectable recurrent disease and 21 healthy blood donors. The sera of non-metastatic breast cancer, patients contained sCD44std and sCD44v6 concentrations similiar to those of healthy blood donors. In sera of patients with distant metastasis from recurrent breast cancer the median values of sCD44std and sCD44v6 were significantly higher (sCD44std: 502 ng/ml, p=0.03; sCD44v6: 193 ng/ml, p = 0.002) in comparison to healthy blood donors and patients with non-metastatic disease (p<0.001 for both parameters). A significant correlation was observed between sCD44v6 serum concentrations and the number of metastasized organs (p=0.0018), serum LDH concentrations (p<0.0001), tumor grading (p=0.025) and the presence of hepatic metastasis (p=0.028). Furthermore, sCD44v6 expression was associated with the patient's responsiveness to second line hormone- or chemotherapy. Non-responders had significantly higher sCD44v6 levels compared with the responder group (median: 447 ng/ml vs 171 ng/ml; p=0.0007). Logistic regression analysis indicated that sCD44v6 serum levels above 250 ng/ml (p =0.033) and the presence of hepatic metastasis (p=0.009) were independent factors predicting an unfavourable response to therapy.

Adult↗