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  • 1
    Electronic Resource
    Electronic Resource
    Review article: anthranoid laxatives and their potential carcinogenic effects (1999)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 13 (1999), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short-term use of these substances is generally safe, long-term use cannot be recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1999.00468.x
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  • 2
    Electronic Resource
    Electronic Resource
    Review article: the potential of combinational regimen with non-steroidal anti-inflammatory drugs in the chemoprevention of colorectal cancer (2005)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 21 (2005), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Non-steroidal anti-inflammatory drugs are chemopreventive agents in colorectal cancer. Non-steroidal anti-inflammatory drugs do not, however, offer complete protection against adenoma and carcinoma development. There is increasing interest in combining non-steroidal anti-inflammatory drugs with agents that target specific cell signalling pathways in malignant and premalignant cells.This review aims to describe the current knowledge regarding the efficacy of peroxisome proliferator-activated receptor-γ ligands, cholesterol synthesis inhibitors (statins), epidermal growth factor signalling inhibitors and tumour necrosis factor-related apoptosis-inducing ligand against colorectal neoplasms and the rationale for combining these drugs with non-steroidal anti-inflammatory drugs to improve efficacy in the chemoprevention of colorectal cancer, a PUBMED computer search of the English language literature was conducted to identify relevant papers published before July 2004.Peroxisome proliferator-activated receptor-γ ligands and statins, both in clinical use, reduce the growth rate of human colon cancer cells in vitro and in rodents models. In vitro, preclinical in vivo and clinical studies have shown efficacy of epidermal growth factor signalling inhibition in colorectal cancer. In vitro, tumour necrosis factor-related apoptosis-inducing ligand induces apoptosis in human colon cancer cells, but not in normal cells. These drugs have all been shown to interact with non-steroidal anti-inflammatory drugs in colorectal cancer cells and/or in rodent models.Combinational regimen are a promising strategy for the chemoprevention of colorectal cancer and should be further explored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2005.02335.x
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  • 3
    Electronic Resource
    Electronic Resource
    Quantification of oral mucositis due to radiotherapy by determining viability and maturation of epithelial cells (2002)
    Oxford, UK : Blackwell Science, Ltd
    Journal of oral pathology & medicine 31 (2002), S. 0 
    Details
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  An in-vitro assay has been developed for quantitative assessment of chemotherapy induced oral mucositis. In the present study this method was evaluated for assessment of irradiation mucositis at a cellular level.Methods:  Ten patients participated in this consecutive study. All patients were treated with conventional fractionated curative postoperative radiotherapy. Prior to, and weekly during, the irradiation course, oral washings were obtained to determine viability of epithelial cells by trypan blue dye exclusion. Maturation of epithelial cells was assessed from smears (Papanicolaou staining). The viability data were compared with the WHO-score for mucositis.Results:  Epithelial cell viability increased during the first three weeks of radiation (P = 0.04), and was seen earlier than the subjective mucosal changes with the WHO-score. Cell maturity shifted from immature and intermediate to mature (P = 0.03).Conclusions:  The cell viability assay can be considered an objective method for following the development of irradiation mucositis, and seems to be more sensitive during the first three weeks of irradiation than the WHO-scoring method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0714.2002.310305.x
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  • 4
    Electronic Resource
    Electronic Resource
    Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas (2004)
    Oxford, UK : Blackwell Science Ltd
    Histopathology 44 (2004), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase-cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard.Methods and results : Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 ± 0.04% in normal mucosa, 0.42 ± 0.04% in adenomas and 1.97 ± 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 ± 0.03%, 0.62 ± 0.06% and 1.78 ± 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P 〈 0.01).Conclusion : Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma–carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.2004.01739.x
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  • 5
    Electronic Resource
    Electronic Resource
    Approaches to lung cancer treatment using the CD3E×GP-2-directed Bispecific Monoclonal Antibody BIS-1 (1997)
    Springer
    Cancer immunology immunotherapy 45 (1997), S. 203-206 
    Details
    ISSN: 1432-0851
    Keywords: Key words Lung cancer ; CD3×EGP-2 ; Bispecific monoclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e. intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab′)2 in combination with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5–8 μg/kg. High plasma concentrations of the inflammatory cytokines tumor necrosis factor α and interferon γ were observed at this dose. Whereas bsAb-dictated antitumour activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal residual disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050433
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  • 6
    Electronic Resource
    Electronic Resource
    Local antitumour treatment in carcinoma patients with bispecific-monoclonal-antibody-redirected T cells (1993)
    Springer
    Cancer immunology immunotherapy 37 (1993), S. 400-407 
    Details
    ISSN: 1432-0851
    Keywords: Immunotherapy ; Bispecific monoclonal antibodies ; T cell targeting ; Inflammation ; T cell activation ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a pilot clinical study carcinoma patients with malignant ascites or pleural exudates have been treated locally with autologous lymphocytes activated ex vivo and redirected towards tumour cells with bispecific monoclonal antibodies. BIS-1, the bispecific monoclonal antibody used in this study, combines specificity against a tumour-associated antigen, AMOC-31, present on carcinomas, with a specificity against the CD3 complex on T lymphocytes. Patients selected for treatment had malignant pleural or peritoneal effusions. Treatment consisted of isolating autologous peripheral blood lymphocytes, ex vivo activation, incubation with bispecific monoclonal antibodies and injection at the effusion site of these BIS-1-redirected lymphocytes. To evaluate the effects of the bispecific monoclonal antibody, five patients received treatments with activated lymphocytes without bispecific antibodies. Effusion samples taken before and at various times after treatment were analysed by immunocytology and for the presence of the soluble factors carcinoembryonic antigen (CEA), interleukin-6 (IL-6), tumour necrosis factor (TNF), C-reactive protein and soluble CD8. In this way both immune activation and anti-tumour activity could be monitored. Conjugate formation between tumour cells and activated lymphocytes was seen as soon as 4 h after injection of BIS-1-redirected activated lymphocytes, followed by a disappearance or reduction of tumour cells after 24–48 h. In parallel with this, the soluble tumour marker CEA decreased in the effusion fluid following injection with the BIS-1-redirected lymphocytes. Furthermore, a steep increase in local granulocyte numbers was observed in the effusion fluid, which reached a maximum 24–48 h after the start of the treatment. Also levels of IL-6 and TNF were greatly elevated. The data suggest tha the treatment induces both antitumour activity and a strong local inflammatory reaction. This is accompanied by no or only minor local and systemic toxicity, i.e. mild fever, which disappeared as the local inflammatory reaction diminished 48–72 h after treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01526797
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  • 7
    Electronic Resource
    Electronic Resource
    Ifosfamide given as a 24-h infusion with mesna in patients with recurrent ovarian cancer: preliminary results (1990)
    Springer
    Cancer chemotherapy and pharmacology 26 (1990), S. S51 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapyresistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5–41 months). No patient who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4–12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2–13+months) and that in the remaining group was 13 months (ranges 3+-24 months) (P〈0.05). This treatment was moderately well tolerated. Grade 3 nausea and vomiting occurred in 27% of cycles and grade 3-4 leukopenia was observed in 47%, but thrombocytopenia was hardly ever found. In eight patients there was a deterioration of renal function. Among a total of 131 cycles, the dose was reduced for only 9 due to myelotoxicity and for 3 due to nephrotoxicity. IFX seems to be active only in patients who have relapsed after responding to previous cytotoxic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685420
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  • 8
    Electronic Resource
    Electronic Resource
    Serotonin metabolism following platinum-based chemotherapy combined with the serotonin type-3 antagonist tropisetron (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 477-482 
    Details
    ISSN: 1432-0843
    Keywords: Key words Serotonin metabolism ; Serotonin type-3 antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antagonist tropisetron as an antiemetic agent. In nine chemotherapy-naive patients with disseminated germ-cell tumors, parameters of serotonin metabolism in both blood and urine were evaluated during two consecutive courses of platinum-based chemotherapy. Serotonin concentrations in platelet-rich plasma and platelet-poor plasma as well as urinary 5-hydroxyindoleacetic acid (5-HIAA) and serotonin levels were measured during the full length of the courses. By means of comparison with the antiemetic agent chlorpromazine, used on day 1 of the first course only, the effect of the serotonin type-3 antagonist tropisetron, the antiemetic agent used during the rest of the courses, on these parameters was studied. Clinical effects were also recorded. No change in the parameters of serotonin metabolism could be demonstrated during either course by the serotonin type-3 antagonist tropisetron. Also in vitro, no effect of tropisetron on the active serotonin uptake by platelets was found. Serotonin levels in platelets showed no correlation with emetic response. However, the platelet serotonin content decreased significantly between the first and the second course (P〈0.01). The significant reduction in platelet serotonin content observed between the first and the second course indicates a depletion of total body serotonin. The role of a serotonin type-3 antagonist might be affected by the altered serotonin equilibrium during later courses of chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685797
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  • 9
    Electronic Resource
    Electronic Resource
    No narcosis for bone marrow harvest in autologous bone marrow transplantation (1984)
    Springer
    Annals of hematology 49 (1984), S. 419-421 
    Details
    ISSN: 1432-0584
    Keywords: Bone marrow transplantation ; Local anesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation. This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00319890
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  • 10
    Electronic Resource
    Electronic Resource
    A case of localized Castleman's disease with systemic involvement: treatment and pathogenetic aspects (1996)
    Springer
    Annals of hematology 73 (1996), S. 47-50 
    Details
    ISSN: 1432-0584
    Keywords: Key words Giant lymph-node ; Hyperplasia ; Castleman's disease ; Radiotherapy ; Interleukin-6 ; Anemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A patient is presented who had Castleman's disease with constitutional symptoms, a palpable supraclavicular/axillar mass, and a microcytic anemia, among other laboratory abnormalities, including elevated levels of interleukin-6. Treatment consisted of irradiation of the involved area, with subsequent disappearance of all symptoms and normalization of the laboratory abnormalities. Iron kinetic studies demonstrated a hypoproliferative erythropoiesis, which normalized after radiotherapy. Hypoproliferative erythopoiesis could not be ascribed to serum inhibitors, since normal burst-forming units were observed in the absence or presence of autologous serum. The role of interleukin-6 in relation to Castleman's disease is highlighted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050201
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