Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 163 records · Page 9Linked to original sources

PubMed1995

Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry.

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Prognostic value of cytosolic thymidine kinase activity as a marker of proliferation in breast cancer.

Thymidine kinase (TK) is involved in DNA synthesis by the salvage pathway. In this study, thymidine kinase (TK) was determined in routinely prepared cytosols of primary tumors from 290 breast-cancer patients. Enzyme activity was measured using a radioenzymatic method optimized for detection of the fetal isoenzyme. High levels of TK (> or = 126 mU/mg protein) were positively associated with histological grade in both pre/peri-and post-menopausal patients. In pre/peri-menopausal patients, high concentrations of TK were also found more frequently in progesterone receptor (PgR)-negative tumors than in PgR-positive samples. In post-menopausal patients, high levels of TK were associated with large tumor size, estrogen receptor (ER) negativity and PgR negativity. In univariate analysis, high levels of TK were strongly associated with shorter overall survival in both pre/peri- (p = 0.001) and post-menopausal patients (p = 0.02). Pre/peri-menopausal patients whose tumors had high levels of TK also had an increased risk of relapse (p = 0.001). In multivariate analysis (including treatment protocol, patient age, lymph-node involvement, tumor size, histological grade, ER and PgR status), TK status was found to be an independent prognostic factor for recurrence-free survival in pre/peri-menopausal patients with a weight similar to that of PgR status. In post-menopausal patients, TK was the only factor selected for overall survival.

Adult↗

PubMed1995

[Information to cancer patients prior to participation in clinical trials. Evaluation of a structured information program].

Informing patients before starting of antineoplastic treatment is important due to the legal aspects of clinical trials and the anxiety and uncertainty felt by the patients. This study evaluates a structured information programme used in a clinical trial. Thirty-four women were interviewed three months after receiving information about trial, using a tape-recorded structured interview. Results showed that the information was well remembered. The patients were glad to have brought a relative to the two consultations, and the time for deliberation in between was well received. The patients viewed written information as an important source of reinformation. The information provided was positively evaluated. Open and detailed information did not undermine the doctor-patient relationship. Instead it allowed patients to understand and participate in treatment decision and helped to reduce their pre-therapy anxiety and uncertainty. The results support expanding structured information programmes to include not only those patients asked to participate in the clinical trial, but all patients beginning longlasting cancer therapy.

Attitude to Health↗

PubMed1995

Characterization of a serine peptidase responsible for the inactivation of endogenous cholecystokinin in human brain.

Depolarization of slices of human cerebral cortex releases cholecystokinin-8 immunoreactivity, only a fraction of which is recovered in intact immunoreactive form in the medium. This suggests that extensive hydrolysis takes place during short incubations. In the presence of diisopropylfluorophosphate, a serine reagent, the recovery is nearly doubled, however, consistent with the involvement of a serine peptidase activity. The latter was characterized by assessing the protective effects of a series of serine protease inhibitors belonging to the families of peptide chloromethylketones or boronic acids. The relative potency of these inhibitors was similar to corresponding values previously found with rat brain slices indicating that a similar serine peptidase activity is responsible for endogenous cholecystokinin inactivation in the two species.

Amino Acid Sequence↗

PubMed1995

Is carboplatin and oral etoposide an effective and feasible regimen in patients with small cell lung cancer?

The combination of carboplatin and etoposide is an active and well-tolerated regimen in the treatment of small cell lung cancer (SCLC). The aim of the study was to confirm whether the efficacy could be maintained if etoposide was administered orally. 106 consecutive, unselected, and untreated patients with SCLC (limited disease (LD) 44; extensive disease (ED) 62) were treated with a combination of carboplatin 300 mg/m2 intravenously (i.v.) day 1 and etoposide 240 mg/m2 orally days 1-3 every 4 weeks for six courses or until progression. If oral treatment was inconvenient, i.v. etoposide (120 mg/m2 days 1-3) was allowed. Thoracic irradiation (45 Gy in 22 fractions, split course) was given after three courses of chemotherapy to 29 patients with LD. Objective response (complete and partial) was seen in 89% (confidence interval (CI) 75-97) of patients with LD and in 53% (CI 40-66) with ED. Complete response was seen in 41% (CI 26-57) of patients with LD and in 8% (CI 2-18) with ED. Median time to progression for responders was 11 months and 6 months for patients with LD and ED, respectively. Corresponding median survival was 15 months (range 1-45 months) and 8.5 months (0-26 months). Myelosuppression comprised the main toxicity. Leucopenia (WHO III-IV) was observed in 20% and thrombocytopenia (WHO III-IV) in 16% of the cases. One patient died of sepsis during leucopenia. Oral treatment was convenient for most patients and therapy well tolerated. However, 9 patients (20%; CI 9-36%) with LD and 26 patients (42%; CI 29-56%) with ED received at least part of the etoposide treatment i.v.. The present study shows that the combination of carboplatin and oral etoposide is active and well tolerated, and may be used on an outpatient basis in patients with small cell lung cancer.

Administration, Oral↗

PubMed1995

Pamidronate infusions as single-agent therapy for bone metastases: a phase II trial in patients with breast cancer.

Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69 breast cancer patients with symptomatic progressive bone metastases were given infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13 infusions or until progressive disease (PD) at any site. No other systemic anticancer therapy was allowed. Pain was measured using a visual analogue scale, mobility using a detailed eight-point questionnaire and analgesic intake using a six-point scale. Improvements in pain, mobility and analgesic scores occurred in 61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40% improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively, despite a one category reduction in analgesic intake in 27% of patients. Using this relatively high dose of pamidronate, symptomatic response was independent of the number of bone metastases and also of infusion rate. The infusions were well tolerated with no major toxicities reported. Pamidronate infusions provide useful palliation for breast cancer patients with symptomatic bone metastases.

Adult↗

PubMed1995

Isolation and characterization of a monoclonal antibody binding to the extracellular domain of the flk-2 tyrosine kinase receptor.

The flk-2 tyrosine kinase receptor is expressed on hematopoietic stem cells and on acute leukemias (AML and ALL). We have isolated a rat monoclonal antibody (71E1) that binds to this receptor with a relative affinity of 5 nM. The antibody immunoprecipitates both murine and human forms of flk-2 and can block receptor activation by its cognate ligand. In addition, 71E1 inhibits the in vitro proliferation of the murine leukemic cell line, M1, that expresses high levels of flk-2. These results suggest that 71E1 may have utility as both a reagent for elucidating the biological role of flk-2 in hematopoiesis and as an immunotherapeutic in the treatment of acute leukemias.

3T3 Cells↗

PubMed1995

Splenic irradiation for chronic autoimmune thrombocytopenic purpura in patients with contra-indications to splenectomy.

We treated by splenic irradiation eight patients with chronic idiopathic thrombocytopenic purpura (ITP, seven cases) or secondary autoimmune thrombocytopenic purpura (one case) who had contra-indications to splenectomy. A total dose of 15 Gy was delivered to the spleen, with left kidney protection. One patient had a good durable response (> 1 year); two patients had a good transient response (of 3 months duration) but they responded again to a second course of irradiation; two patients had only partial response, but have required no other treatments for 2 years; the three remaining patients had no response. Side-effects were minor. Therefore splenic irradiation appears to be a therapeutic option in patients with chronic ITP who have contra-indications to splenectomy.

Aged↗

PubMed1995

Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases.

We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high-dose dexamethasone (DXM, 40 mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 x 10(9)l (range 6-26 x 10(9)/l) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM. Five patients had a response (i.e. platelet count at least doubled and increased by > 20 x 10(9)/l), including one almost complete remission and four minor responses (MR). Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side-effects (systemic hypertension with stroke and insulin-dependent diabetes, respectively). In our experience, high-dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side-effects in some cases.

Adult↗

PubMed1995

Glomerular injury in chronic myelomonocytic leukemia.

Among 825 cases of de novo myelodysplastic syndromes (MDS) diagnosed over a period of 13 years in our center, 4 had clinically significant glomerulopathy. All 4 fulfilled diagnostic criteria of chronic myelomonocytic leukemia (CMML), and could be classified in the low or intermediate risk groups according to two scoring systems. Presenting symptoms of renal involvement were edema in 3 cases and acute renal failure in the remaining patient. Three patients had the nephrotic syndrome. Renal biopsy (performed in 2 cases but considered as contraindicated in the other cases) showed AL amyloidosis on one case and extracapillary glomerulonephritis in the other case. The 4 patients were treated with V16 or hydroxyurea and two had renal improvement. Only one previous case of MDS associated with glomerulopathy has been reported before and also very probably had CMML. This, and the response of renal disease to chemotherapy in 2 of our patients suggests a possible relationship between the two disorders. More systematic investigation of glomerular function, in CMML, could possibly disclose a higher incidence of cases of glomerular injury in this type of MDS.

Aged↗

PubMed1995

Dehydroascorbate reductase activity in bovine lens.

The bovine lens was studied for the presence of dehydroascorbate reductase activity. The activity was found to be restricted primarily to the mitochondrial fraction isolated from the cortex-epithelial fraction of the tissue. It was not detectable in the cytosolic fraction. The Km of reaction with dehydroascorbate was approximately 0.45 mM. These studies suggest that the reduction of dehydroascorbate to ascorbate in the mitochondria takes place enzymatically as well as nonenzymatically, GSH being the source of reducing electrons in both the cases. The enzymatic mechanism may assume a greater role in situations of oxidative stress which lead to GSH depletion. The presence of this enzyme in the mitochondria is considered with a normally more severe oxidative condition therein.

Animals↗

PubMed1994

[The significance of chemotherapy for survival after recurrent breast cancer. A population based study of patients treated in the 1950's, 1960's and 1970's].

In a population-based study survival after recurrence was compared in three cohorts of patients each with a primary diagnosis of breast cancer in either 1959, 1969 end 1979. The use of chemotherapy after recurrence in these cohorts was either none, sporadic or widespread. This allowed a retrospective analysis of the survival impact of chemotherapy. Our data suggest that chemotherapy in recurrent breast cancer prolongs survival by 9.5 months in patients who survive more than two weeks from the start of treatment for their recurrence, given the basic assumption that the natural history of breast cancer and the influence of endocrine therapy have not changed significantly during the 20-year period covered by the study.

Adult↗

PubMed1994

[Chemotherapy in metastasing breast cancer--is it beneficial?].

Carcinoma of the breast is the most common type of cancer among women in Denmark (3,000 new cases a year). About half of the patients will at some time develop metastases. Treatment of extended disease is controversial. Public discussion has focused on whether it is desirable to treat these patients with chemotherapy or not. This case story describes four cases with long term survival (nine, ten, 14, 19 years after début of metastases). This underlines that it is possible within the existing types of treatment to achieve both extended survival and acceptable life quality. The doctor's dilemma is that he does not know whom treatment helps. We conclude that treatment should be offered to all patients. This will be of benefit to the whole group.

Adult↗

PubMed1994

[Support to spouses of patients with cancer].

Psychosocial problems frequently arise in the families of cancer patients. Using a questionnaire, information about the problems experienced by 120 spouses to cancer patients was collected. The response rate was 85%. The results show that the patient and the children are the most important persons in supporting the spouses. Sixty-one percent felt relieved of having somebody to talk to about their problems. The amount of contact to friends and family mainly remained unchanged. Approximately 1/3 of the spouses had to work more than the normal 37 hours a week, which compromised their abilities to support the patients. Professional help was sought by 1/4 of the spouses in an attempt to solve their problems in relation to the patient's disease. Men are more likely to have their problems solved by professional support than women. Among the spouses there is a great wish for information and support offered primarily by the oncological department. It is concluded that the spouses needed more support, wanted more information, and asked for the possibilities to talk about their emotional problems. This need is emphasized by the present strategy in the health system, where still more patients are treated on an out-patient basis. It is important that the professional support is offered from the time of the diagnosis.

Adult↗

PubMed1994

[Use of Q10 in cancer patients].

The aim of the study was to quantify the use of alternative therapy, and especially the use of coenzyme Q10 in cancer patients. The study was conducted as a cross-sectional questionnaire study. During a two week period all in- and out-patients in the Department of Oncology and Haematology, Odense University Hospital, were asked about their use of alternative treatment. A total of 769 questionnaires were answered, a response rate of 97%. Of these patients 343 (45%) used alternative medicine, and 137 (18%) used coenzyme Q10. The use of alternative medicine and coenzyme Q10 was more frequent in women than in men, and in patients with recurrent disease than in patients with primary disease. A search of the literature revealed no documentation for the use of coenzyme Q10 either as an antineoplastic agent or as an adjunct to antineoplastic therapy. It might be possible that coenzyme Q10 can protect the myocardium from doxorubicin induced damage.

Adult↗

PubMed1994

Flow cytometric DNA ploidy defines patients with poor prognosis in node-negative breast cancer.

Flow cytometric DNA analysis was performed on fine-needle aspirates from frozen tumour biopsies from 421 node-negative, non-adjuvantly-treated breast-cancer patients with a median observation time of 6.75 years. Among premenopausal patients (n = 175), those having at least one DNA "hypoploid" subpopulation defined as DNA index (DI) < 0.96 or 1.44 < or = 1.92 (n = 81) were characterized by early recurrences (log-rank p = 0.05), Wilcoxon p = 0.007), poor overall survival (OS) (p < 0.001) and poor survival after recurrence (p < 0.001). In the postmenopausal group (n = 246), there were no significant difference among 7 different DI classes regarding either recurrence-free survival (RFS) or OS. S-phase fraction (SPF), divided into quartiles, predicted OS in premenopausal patients only (p = 0.02). Conventional multivariate Cox analysis of OS in the premenopausal group revealed hypoploidy to be the only independent prognostic factor involving a relative risk (RR) of 22.8. Age < or = 40 years was of marginal significance, whereas SPF, histological grade (WHO), oestrogen and progesterone receptor (PgR) content, tumour size and number of lymph nodes removed were excluded from the model. Application of the conventional Cox model to the premenopausal group regarding RFS was found inappropriate due to lack of proportionality of the hazards of hypoploidy due to lack of proportionately of the hazards of hypoploidy, SPF and histological grade. However, introduction of time-dependent co-variates using 2 years as cut-off level showed hypoploidy with a RR of 3.52 and age < or = 40 years with a RR of 3.28 to be independent prognostic factors. In the postmenopausal group, the conventional Cox model identified the number of lymph nodes removed to be the only independent prognostic factor regarding RFS as well as OS, whereas SPF < 9% (lowest quartile) was of marginal significance in RFS analysis. Hypoploidy was correlated to high SPF, low PgR content and low differentiation, indicating that hypoploid tumours proliferate rapidly and hormone-independently. These patients may therefore benefit from adjuvant chemotherapy administered while tumour burden and risk of drug resistance are still low.

Adult↗

PubMed1994

Formation of pressure waves during in vitro excimer laser irradiation in whole blood and the effect of dilution with contrast media and saline.

Pressure waves during excimer laser ablation of vascular tissue may be responsible for complications of coronary excimer laser angioplasty. In this experimental study, pressure waves were measured during excimer laser irradiation in blood and contrast media using a polyvinilidenefluoride hydrophone. At a distance of 4 mm lateral to the tip of a 1.7 mm multifiber laser catheter, excimer laser irradiation in blood resulted in a linear increase of peak pressures from 1,365 +/- 165 kPa at 30 mJ/mm2 to 2,866 +/- 404 kPa at 60 mJ/mm2. In contrast media, peak pressure increased from 3,172 +/- 573 kPa (30 mJ/mm2) to 5,763 +/- 467 kPa (60 mJ/mm2). Contrast media and saline were added to blood. At a concentration of 60% contrast in blood, a 3.4 fold increase of peak pressures was documented as compared to pure blood. Further increase of the concentration did not result in higher pressure waves. Concentrations of saline in blood of 90% and 96% reduced the peak pressures by 16% and > 50%, respectively, as compared to pure blood.

Angioplasty, Laser↗

PubMed1994

The cardioprotector ADR-529 and high-dose epirubicin given in combination with cyclophosphamide, 5-fluorouracil, and tamoxifen: a phase I study in metastatic breast cancer.

The purpose of this study was to determine the maximal tolerable dose (MTD) of epirubicin and ADR-529 given in combination with cyclophosphamide, 5-fluorouracil, and tamoxifen. A total of 64 breast cancer patients with locally advanced disease or a first metastatic event were included. Using fixed doses of cyclophosphamide, 5-fluorouracil, and tamoxifen, cohorts of ten patients were treated with escalating doses of epirubicin and ADR-529. With the use of protocol criteria specifying evaluation after the first course, the MTD was not reached. Dose reductions carried out due to hematologic toxicity during the first four courses made it impossible to escalate doses of epirubicin beyond 80 mg/m2 given together with ADR-529 600 mg/m2. The vascular toxicity of ADR-529 necessitated central venous access in a number of patients. For phase III evaluation of ADR-529 given together with cyclophosphamide, epirubicin, 5-fluorouracil, and tamoxifen (CEF/TAM) we recommend using epirubicin/ADR-529 at 60/600 mg/m2. Together with evaluation of the cardioprotective properties of ADR-529, we recommend evaluating the impact of ADR-529 on the efficacy of cytotoxic therapy and investigating further the toxicity of ADR-529.

Adult↗