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C Seynaeve

Publications and source records attributed to C Seynaeve.

At least 55 records · Page 3Linked to original sources
PubMed1999

Involvement of LFA-1 in hepatic NK cell (pit cell)-mediated cytolysis and apoptosis of colon carcinoma cells.

BACKGROUND/AIMS: Previous studies have shown that hepatic natural killer (NK) cells, also called pit cells, have a higher cytotoxicity against certain tumor cells and have a higher expression of the cell adhesion molecule CD11a as compared with blood NK cells. We further investigated the involvement of the adhesion molecules, reported to be involved in target cell killing by blood NK cells, in pit cell-mediated colon carcinoma cell killing. METHODS: 51Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. Adhesion of pit cells to CC531s monolayers was quantitated. RESULTS: Flow cytometric analysis showed that pit cells expressed CD2, CD11a, CD18 and CD54. CC531s cells expressed only CD54. Treatment of freshly isolated pit cells with monoclonal antibodies (mAbs) to CD11a and CD18 inhibited not only the pit cell-mediated CC531s cytolysis but also the pit cell-induced apoptosis of CC531s cells. The combination of mAbs to CD11a, CD18 and CD54 further increased the inhibition of pit cell-mediated CC531s cytolysis and apoptosis. Anti-CD2 mAb did not affect these processes. The binding of pit cells to CC531s cells was also inhibited by anti-CD11a, and CD18 mAbs, but not by anti-CD2 mAb. Anti-CD54 mAb reduced the target cell killing and the binding only slightly. CONCLUSIONS: These results indicate that CD11a/CD18 (LFA-1) present on pit cells plays an important role in pit cell-mediated target cell adhesion, lysis and apoptosis. This finding might explain why pit cells, which have a higher expression of LFA-1 as compared to blood NK cells, are more cytotoxic against tumor cells as compared to blood NK cells.

Animals↗
PubMed1999

The reason for confining the use of adjuvant chemotherapy in soft tissue sarcoma to the investigational setting.

Adjuvant chemotherapy for soft tissue sarcoma has been the subject of many studies. Most studies have been nonrandomized and therefore by definition inconclusive. In addition, most of the 14 performed randomized studies have had small sample sizes. A meta-analysis on the data of these 14 studies suggested a possible survival improvement, albeit not significant. The outcome of the meta-analysis should be interpreted with caution in view of the fact that in 18% of patients, histology data were lacking; ineligibility rates in included studies were high; central pathology was not uniformly performed; and in 6% of patients, sarcomas other than soft tissue sarcomas were included. Because it is generally recommended that meta-analyses of small randomized trials are used only to generate hypotheses for more reliable randomized trials, it is argued that adjuvant chemotherapy in soft tissue sarcomas should remain confined to the investigational setting.

Antineoplastic Agents↗
PubMed1999

Survival in hereditary breast cancer associated with germline mutations of BRCA2.

PURPOSE: Breast cancer in BRCA1 and BRCA2 gene-mutation carriers may differ from so-called sporadic breast cancer in clinical features and behavior. These potential differences may be of importance for the prevention, screening, and, ultimately, treatment of breast cancer in women with such germline mutations. Thus far, there have been very few studies on the survival of BRCA2-associated breast cancer patients. PATIENTS AND METHODS: We determined the disease-free and overall survival of 28 breast cancer patients from 14 consecutive families with eight different BRCA2 germline mutations. These patients' survival and tumor characteristics were compared with those of a control group of 112 sporadic breast cancer patients matched to them by age and year of diagnosis. RESULTS: The 5-year disease-free survival was 52% for each group (P =.91); the overall survival was 74% for BRCA2 carriers and 75% for sporadic cases (P =.50). At the time of diagnosis, tumors from the BRCA2 carriers were borderline significantly larger in comparison to the tumors in sporadic cases (P =.05), but axillary nodal status was not significantly different in the two groups (node-negativity, 63% v 52. 8%, respectively; P =.34). With respect to steroid receptor status, BRCA2-associated tumors were more likely to be steroid receptor-positive, especially regarding progesterone receptor status (100% v 76.7% positive, respectively; P =.06). Stage-adjusted recurrence and death rates were nonsignificantly better for BRCA2 cases (hazard ratios of 0.84 and 0.59 [P =.61 and P =.19], respectively). In contrast, after 5 years, the rate of metachronous contralateral breast cancer in BRCA2 patients was 12% (v 2% in controls; P =.02). CONCLUSION: Patients with hereditary breast cancer due to BRCA2 have a similar prognosis when compared with age-matched sporadic breast cancer patients. Contrary to our previous observation regarding BRCA1-associated breast cancer, BRCA2 tumors tended to be steroid receptor-positive, instead of steroid receptor-negative.

Actuarial Analysis↗
PubMed1999

High-dose chemotherapy in adult sarcomas: no standard yet.

The management of patients with sarcoma involves a multidisciplinary approach, with surgery, radiotherapy, and chemotherapy all playing their part. The role of high-dose chemotherapy in this heterogeneous and rare disease remains controversial and unproven. Adult soft tissue sarcomas (STS) generally are poorly responsive to standard chemotherapy, with doxorubicin (DOX) and ifosfamide (IFOS) being the only available agents showing response rates of greater than 20%. Combination regimens generally do not add efficacy, but do add toxicity. For both active agents, a dose-response relationship has been shown. Therefore, and in the absence of new and better drugs or schedules, dose-intensifying and even high-dose chemotherapy regimens (HDCT) with cellular support have been studied. Unfortunately, most of these trials were noncontrolled, studying heterogeneous patient groups. Furthermore, these strategies never resulted in a significantly longer overall survival (OS), and therefore remain highly investigational. Primarily, the search for new active drugs should be encouraged. Although HDCT cannot be considered common practice in STS, the role of this strategy as consolidation therapy in well-defined subsets of patients, using prognostic factors, could be explored further in carefully designed studies. The Ewing tumor family (ET), as a distinct entity, is more responsive to chemotherapy and considered a systemic disease. Results from small, noncontrolled studies indicate that consolidation therapy by megatherapy and hematologic support contributes to an improved outcome in "high-risk" Ewing patients compared with historical controls. However, the exact role of HDCT remains to be determined in properly designed randomized studies with well-defined patient groups and appropriate sample sizes. The collaboration between cooperative groups in the design and execution of randomized studies with appropriate sample sizes should be encouraged. This approach might provide us with essential answers enabling further progress. In addition, each sarcoma patient should, as much as possible, be treated within the context of a properly designed study.

Adult↗
PubMed1998

[Chemotherapy in metastasized breast carcinoma].

Metastatic breast cancer is still an incurable disease. Standard hormonal and chemotherapeutic treatment modalities yield at the best a survival advantage of 1 to 2 years. However, palliation is still the second, very important goal of treatment for metastatic disease. First-line chemotherapeutic treatment with an anthracycline-containing regimen induces a response in about half the patients. In second-line treatment docetaxel is an effective agent even in patients failing first-line therapy with an anthracycline-containing regimen. There is no effective standard third-line chemotherapy scheme.

Anthracyclines↗
PubMed1998

Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1.

BACKGROUND: Hereditary breast cancer has been associated with mutations in the BRCA1 and BRCA2 genes and has a natural history different from sporadic breast cancer. We investigated disease-free and overall survival for patients with a proven BRCA1 alteration. METHODS: We estimated disease-free and overall survival for 49 Dutch patients from 19 consecutive families with a proven specific BRCA1 mutation and one family with strong evidence for linkage to the BRCA1 gene. We compared clinical outcome and data on tumour size, histology, axillary nodal status, contralateral breast cancer, and oestrogen-receptor and progesterone-receptor status with those of 196 patients with sporadic breast cancer, matched for age and year of diagnosis. FINDINGS: Disease-free survival for BRCA1 and sporadic patients at 5 years was 49% (95% CI 33-64) and 51% (43-59), respectively (p=0.98). Overall survival at 5 years was 63% (47-76) and 69% (62-76), respectively (p=0.88). Recurrence and death rates did not differ significantly between groups. Hazard ratios for recurrence and death among BRCA1 patients were 1.00 (0.65-1.55) and 1.04 (0.63-1.71) relative to sporadic patients (p=0.88), and these did not differ significantly after adjustment for prognostic factors. Patients with BRCA1-associated breast cancer had twice as many progesterone-receptor-negative tumours (p<0.005) and development of contralateral breast cancer was four to five times as frequent as in the sporadic group (p<0.001). INTERPRETATION: We showed that disease-free and overall survival were similar for sporadic and hereditary breast cancer in the presence of different tumour characteristics, which has implications for screening prophylactic therapy, and different treatments of hereditary breast cancer.

Adult↗
PubMed1998

Imaging surface and submembranous structures with the atomic force microscope: a study on living cancer cells, fibroblasts and macrophages.

Atomic force microscopy (AFM) has been used to image a wide variety of cells. Fixed and dried-coated, wet-fixed or living cells were investigated. The major advantage of AFM over SEM is the avoidance of vacuum and electrons, whereas imaging can be done at environmental pressure and in aqueous conditions. Evidence of the successful application of AFM in biological imaging is provided by comparing results of AFM with SEM and/or TEM. In this study, we investigated surface and submembranous structures of living and glutaraldehyde-fixed colon carcinoma cells, skin fibroblasts and liver macrophages by AFM. Special attention was paid to the correct conditions for the acquisition of images of the surface of these cells, because quality SEM examinations have already been abundantly presented. AFM imaging of living cells revealed specific structures, such as the cytoskeleton, which were not observed by SEM. Membrane structures, such as ruffles, lamellipodia, microspikes and microvilli, could only clearly be observed after fixing the cells with 0.1% glutaraldehyde. AFM images of living cells were comparable to SEM images of fixed, dried and coated cells, but contained a number of artefacts due to tip-sample interaction. In addition, AFM imaging allowed the visualization of cytoplasmic submembranous structures without the necessity for further preparative steps, allowing us: (i) to follow cytoskeletal changes in fibroblasts under the influence of the microfilament disrupting agent latrunculin A; (ii) to study particle phagocytosis in macrophages. Therefore, in spite of the slow image acquisition of the AFM, the instrument can be used for high-resolution real-time studies of dynamic changes in submembranous structures.

Adenocarcinoma↗
PubMed1998

Hepatic stellate cells and liver retinoid content in alcoholic liver disease in humans.

Body retinoids are stored in the lipid droplets of hepatic stellate (Ito) cells. In chronic liver disease, the stellate cells differentiate into myofibroblast-like cells, a process whereby they lose their retinoid-containing lipid droplets. We studied the relation between liver retinoid content, the number of lipid droplets per stellate cell, and the number of stellate cells per mm2 in human alcoholic liver disease. Semithin sections of liver biopsies from normal subjects and patients with early (steatosis, inflammation, and mild fibrosis) and late (cirrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease were morphometrically evaluated. Liver retinoid content was determined by HPLC. In normal patients, liver retinoid content was 901 +/- 213 IU/g of liver (mean +/- SEM). There was a decrease in liver retinoid content in early alcoholic liver disease (409 +/- 50 IU/g) and a further reduction in cirrhosis (153 +/- 50 IU/g). In patients with acute alcoholic hepatitis, retinoid content was strikingly low (5.2 +/- 1.8 IU/g). There was a progressive decrease in the number of stellate cells per mm2 associated with progressive liver damage. We found a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups (overall correlation: 0.71). In normal subjects, the mean number of lipid droplets per stellate cell was 7.4 +/- 0.7. In patients with early alcoholic liver disease and in patients with alcoholic cirrhosis, this value was increased to 13.6 +/- 0.8 and 10.4 +/- 2.0, respectively. In patients with acute alcoholic hepatitis, only a few lipid droplets were present (4.2 +/- 0.5). There was a good correlation between liver retinoid content and mean number of lipid droplets in normal patients (r = 0.58). In alcoholic cirrhosis, however, correlation was poor (r = 0.34). In early alcoholic liver disease, the correlation was absent (r = 0.004). In conclusion, the major finding of our study is that the correlation between the mean number of lipid droplets per stellate cell and liver retinoid content varies according to the hepatic pathology considered. Marked lipid droplet accumulation occurs in stellate cells in early alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but there is no correlation between the mean number of lipid droplets per stellate cell and liver retinoid content. Therefore, not retinoids but probably lipids are responsible for the accumulation of lipid droplets. We also find that there is a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups. Finally, we confirm the decrease in hepatic retinoid content that occurs in alcoholic liver disease in humans, even at the early stages of the disease.

Biopsy↗
PubMed1997

[Multidisciplinary treatment of superior sulcus (Pancoast) tumors].

Ten patients with a Pancoast tumour, seven with pulmonary carcinoma, three with a soft tissue tumour, were treated surgically with or without preoperative chemotherapy or external radiotherapy, and with postoperative external radiotherapy mostly in combination with brachytherapy using a flexible intraoperative template. The results were highly variable, e.g. one patient died after three months, another was still alive without tumour after 36 months. Optimal treatment requires cooperation of experienced surgeons, radiotherapists and medical oncologists.

Adult↗
PubMed1996

Adverse effect on bone marrow protection of prechemotherapy granulocyte colony-stimulating factor support.

BACKGROUND: Increased proliferation of endogenous bone marrow progenitor cells in response to the administration of hematopoietic growth factors, followed by reduced cell cycling or entrance of the cells into a quiescent state upon withdrawal of the growth factors, may have clinically relevant effects on the tolerance of the hematopoietic system to subsequent myelotoxic treatments. PURPOSE: We investigated the ability of granulocyte colony-stimulating factor (G-CSF) to protect progenitor cells in the bone marrow of cancer patients from the toxic effects of subsequent treatments with chemotherapeutic agents. METHODS: Thirty-six patients with histologically documented, locally advanced or metastatic breast cancer were randomly assigned to receive doxorubicin once every 3 weeks at a dose of 75 mg/m2 and cyclophosphamide at a dose of 1000 mg/m2, with G-CSF administered either before and after chemotherapy (18 patients) or after chemotherapy only (18 patients). For prechemotherapy administration of G-CSF, recombinant human methionyl (r-met Hu) G-CSF was administered subcutaneously to patients twice per day for 5 days at a dose of 5 micrograms/kg, with the last dose given 48 hours before the start of chemotherapy. For postchemotherapy administration of G-CSF, r-met Hu G-CSF was administered subcutaneously to patients once per day for 7 days at a dose of 5 micrograms/kg, with the first dose given 24 hours after chemotherapy. RESULTS: The incidence or the duration of grade 4 neutropenia was not reduced in all patients by the use of prechemotherapy G-CSF; the incidence over all cycles of chemotherapy was 74% for patients treated with prechemotherapy and postchemotherapy G-CSF and 66% for patients treated with postchemotherapy G-CSF only (two-sided P, adjusted for dose = .21) and the median duration in both treatment arms was 3 days (two-sided P = .19). Unexpectedly, the incidence of grades 3 and 4 thrombocytopenia was much greater in patients who received prechemotherapy G-CSF compared with those who did not (54% versus 6%, respectively, over all chemotherapy cycles; two-sided P, adjusted for dose < .001). No difference in the decrease in hemoglobin level (adjusted for red blood cell transfusions) between patients in the two treatment arms was observed. CONCLUSIONS AND IMPLICATIONS: No beneficial effects were associated with the administration of G-CSF to cancer patients prior to chemotherapy. The observation of more severe thrombocytopenia in patients treated with prechemotherapy G-CSF led us to conclude that the proliferation of progenitor cells was still increased 48 hours after the last dose of G-CSF and that the administration of chemotherapy at or within this time period actually worsens the toxic effects on bone marrow. This result has important ramifications for the design of clinical cancer treatment protocols, especially those that involve shortened intervals between cycles of chemotherapeutic agent administration.

Adult↗
PubMed1996

The role of adhesion molecules in the recruitment of hepatic natural killer cells (pit cells) in rat liver.

Previous studies showed that blood large granular lymphocytes (LGL), which possess natural killer (NK) activity, develop within rat liver sinusoids into high-density (HD) and subsequently into low-density (LD) pit cells which show an increasing level and spectrum of tumor cytotoxicity. In this study, we investigated the role of adhesion molecules, such as CD2, CD11a, CD18, and CD54 in the recruitment of pit cells to the liver. Immunostaining for electron microscopy, and two color flow cytometry showed that most pit cells expressed CD2, CD11a, CD18, and CD54. After intravenous injections into rats with anti-CD2, anti-CD11a, and anti-CD18 antibodies, the number of pit cells per square millimeter in frozen sections of liver tissue decreased. Treatment of rats with zymosan increased the number of pit cells fivefold, whereas subsequent treatment with anti-adhesion-molecule antibodies resulted in approximately 60% lower number of pit cells. Anti-CD54, supposed to block CD54 expression on sinusoidal endothelial cells, also decreased the number of pit cells. The number of blood LGL was, however, not affected by these antibodies. These results indicate that blocking of CD2, CD11a, CD18, and CD54 antigens on blood LGL and/or liver endothelium decreased the number of pit cells in the liver. These adhesion molecules therefore play an important role in the recruitment of pit cells in the liver.

Animals↗
PubMed1996

Novel endocrine therapies in breast cancer.

Endocrine therapy of breast cancer consists of a variety of both medical and surgical ablative treatment modalities, but ablative therapy is increasingly replaced by medical treatment. Most endocrine therapies have more than one endocrine effect, frequently together with direct growth inhibitory actions via receptors. Endocrine therapy can be effective in all phases of the disease, but curative only in early disease while in advanced cancer it can only prolong survival. In the past decade the number of available endocrine agents has been drastically increased. Novel approaches in the endocrine therapy of breast cancer are application of new antiestrogens, antiprogestins, new potent aromatase inhibitors, analogues of luteinizing hormone-releasing hormone (LHRH-A) and somatostatin, inhibitors of prolactin secretion, vitamin A and D analogues, bisphosphonates, growth factor antagonists, tyrosine protein kinase inhibitors, protease inhibitors, inhibitors of angiogenesis, radiolabeled hormones and monoclonal antibodies. New cell biological factors such as oncogenes and suppressorgenes, secretory proteins and membrane receptors can be used not only as prognostic factors but also for prediction of type of response to endocrine and chemotherapy. Thus, these cell biological parameters can be used to select high and low risk patients, type of systemic treatment, and can also be used as targets for new treatment modalities. Future studies on treatment of all stages of disease will increasingly focus on promising combined treatment modalities.

Antineoplastic Agents, Hormonal↗
PubMed1992

Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis. A multicentre, double-blind, randomised, parallel group study. Ondansetron Study Group.

A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female) scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated in a randomised, double-blind, parallel group study to evaluate the efficacy and safety of three intravenous dose schedules of ondansetron in the prophylaxis of acute nausea and emesis. One hundred and eighty two patients received a loading dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1); 180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group III) respectively, followed by a 24 h placebo infusion. Complete and major control (less than or equal to 2 emetic episodes) of acute emesis was achieved in 74% of patients in group I, 78% in group II and 74% in group III. Seventy seven per cent of the patients in group I, and 75% of patients in groups II and III respectively experienced no or mild nausea during the 24 h observation period. A retrospective stratification of the efficacy data on the basis of patient gender showed the response rate in females to be significant lower (43% vs 67%; less than 0.001). Ondanestron was well tolerated; mild headache was the most commonly reported adverse event (11% of patients) with a similar incidence in the three groups of patients. In conclusion, a single intravenous dose of 8 mg of ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose given as either a single dose of a continuous infusion in the prophylaxis of acute cisplatin-induced emesis.

Adult↗
PubMed1991

Controlling cancer chemotherapy-induced emesis. An update.

Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3-6 mg.kg-1.d-1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.

Antiemetics↗
PubMed1991

Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear.

Both radiotherapy and chemotherapy for cancer are capable of causing severe nausea and vomiting, which formerly often interfered with the patient's compliance to treatment. The basic pathway and pharmacological mechanisms involved in this are still poorly understood. The recent discovery, however, that 5-HT3 receptor antagonists can prevent or greatly reduce chemotherapy-induced emesis led to a re-evaluation of the sequence of events occurring in the protective emetic reflex, which are reviewed in this paper. The vomiting centre co-ordinates the incoming and outgoing information, and is thought to be represented by complex interactions between different adjacent areas in the brainstem. Whether the main role in the emetic reflex arch is accomplished by either the central part (chemoreceptor trigger zone) or the peripheral part (gastro-intestinal tract) needs further confirmation A more important role, however, of the vagal nerve and the gastro-intestinal tract is generally accepted. The neurotransmitter serotonin (5-HT) appears to play a major role in chemotherapy-induced emesis via the 5-HT receptor. These indications could form the basis for further investigations into the involvement of other neurotransmitters, and the character of their interactions.

Animals↗
PubMed1991

Randomised phase II trial of carboplatin and iproplatin in advanced urothelial cancer.

47 patients with advanced urothelial cancer and no prior chemotherapy were randomly assigned to therapy with either carboplatin or iproplatin. Both platinum analogues were administered intravenously every 28 days at doses of 400 mg/m2 carboplatin and 300 mg/m2 iproplatin. None of 14 evaluable patients treated with carboplatin responded. Therefore, this arm was closed and from then on all eligible patients were registered on the iproplatin arm. 5 of 29 evaluable patients treated with iproplatin achieved a partial response (17%) for a median duration of 27 weeks (range 22-37). Iproplatin did not induce renal function disturbance. Gastrointestinal toxicity was mild to moderate. Bone marrow toxicity predominantly consisted of thrombocytopenia and required platelet transfusions in 13% of patients. 2 patients developed hypersensitivity reactions. It is concluded that the bone marrow toxicity and the chance of hypersensitivity render iproplatin an unattractive alternative to cisplatin.

Adult↗