The importance of the VEGF-load in platelets in cancer patients.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
E van Marck
Publications and source records attributed to E van Marck.
Methotrexate-associated liver toxicity in a patient with breast cancer: case report and literature review.
A patient with breast cancer developed severe asthenia, accompanied with progressively increasing transaminases, during adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and 5-fluorouracil). Additional blood tests and imaging were negative. A liver biopsy revealed a grade II toxic hepatitis. Because methotrexate was suspected to be the cause of the hepatotoxicity, the administration of this drug was stopped and mitoxantrone was given instead. A recovery of clinical symptoms and normalisation of the liver function tests was observed afterwards. In that sense, mitoxantrone appears to be a valuable alternative to methotrexate in cases of hepatotoxicity in patients with breast cancer. An overview of the literature regarding methotrexate hepatotoxicity is presented.
Antineoplastic Combined Chemotherapy Protocols↗
Expression profile of telomerase subunits in human pleural mesothelioma.
Using the TRAP assay, telomerase activity was previously detected in over 90% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultures (MCCs), suggesting that telomerase re-activation occurs during multi-step mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein (hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in six MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all malignant and non-malignant serosal cells and tissues. Three alternatively spliced hTERT transcripts were detected in all telomerase-positive samples, whereas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These results indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expression can play a critical role in MM carcinogenesis. While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-malignant serosal lesions.
Blotting, Western↗
Schistosoma mansoni infection causing diffuse enteric inflammation and damage of the enteric nervous system in the mouse small intestine.
Schistosomiasis mansoni is a major health problem, mainly occurring in developing countries. A large proportion of infected individuals suffers from motility-related gastrointestinal problems. In the present study, the diffuse inflammatory response in the small bowel wall, as compared to the egg-induced granulomatous inflammation, was investigated. For this purpose, OF1 mice infected with Schistosoma mansoni 8-16 weeks prior to the experiment, and uninfected control mice were studied. The ileum showed both a diffuse mucosal inflammation as well as a granulomatous reaction. The diffuse mucosal inflammation caused an increase in the thickness of the mucosa, with blunting of the villi. A significant, transient increase of thickness of the muscularis propria after 12 weeks of infection was noted. There was an infection-related mast cell infiltrate in the muscularis propria, consisting of formalin fixation-insensitive connective tissue mast cells. Ganglionitis of the myenteric plexus was noted. Rarely, ganglia of the myenteric plexus contained apoptotic cells. A general pharmacological set of experiments showed a significant increase in intestinal contractility, both to exogenously administered, as well as to endogenously released neurotransmitters. Our results demonstrate that S. mansoni infection in the mouse ileum leads to diffuse specific enteric inflammation that is associated with an enhanced response to contractile agents.
Animals↗
Influence of surgical bladder reduction on urodynamic parameters: three techniques investigated in a rat model.
PURPOSE: Bladder wall wrapping and invagination have been used for the surgical treatment of the underactive detrusor and improvement of bladder emptying has been described. In a rat model we investigated the evolution in time of urodynamic parameters after 3 techniques of surgical bladder reduction. MATERIAL AND METHODS: Female Wistar rats underwent at random, a bladder reduction with vertical wrapping, the horizontal variant or invagination of the wall. Cystometry was performed before and 30 minutes after surgery, and after 1, 5 and 10 weeks. Sham operated animals had cystometries performed at day 1 and after 1, 5 and 10 weeks. At week 10 contraction of four differently orientated detrusor strips was examined in vitro. A histological study was done. RESULTS: Contraction pressure was not improved in vivo after 10 weeks follow-up. Capacity, despite an early significant reduction, became slightly higher than presurgery in both wrapping groups and even significantly higher in the invagination group. In each group residual volume almost doubled. In vitro some strips containing operated parts did contract more strongly than controls but not significantly. Strips which contain operated parts showed slightly increased fibrosis in the invagination and the vertical wrapping group and a huge amount of fibrosis in the horizontal wrapping group. CONCLUSIONS: This experiment indicated that the rationales behind the techniques of surgical bladder reduction are not correct. The partial successes in men may be explained by the original intrinsic deficiencies of the detrusor which prevent a secondary bladder enlargement as reaction to the volume reduction.
Animals↗
Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.
Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
Antigens, CD↗
Computer-assisted differential diagnosis of malignant mesothelioma based on syntactic structure analysis.
BACKGROUND: Malignant mesothelioma, a mesoderm-derived tumor, is related to asbestos exposure and remains a diagnostic challenge because none of the genetic or immunohistochemical markers have yet been proven to be specific. To assist in the identification of mesothelioma and to differentiate it from other common lesions at the same location, we have tested the performance of syntactic structure analysis (SSA) in an automated classification procedure. MATERIALS AND METHODS: Light-microscopic images of tissue sections of malignant mesothelioma, hyperplastic mesothelium, and adenocarcinoma were analyzed using parameters selected from the Voronoi diagram, Gabriel's graph, and the minimum spanning tree which were classified with a K-nearest-neighbor algorithm. RESULTS: Results showed that mesotheliomas were diagnosed correctly in 74% of the cases; 76% of the adenocarcinomas were correctly graded, and 88% of the mesotheliomas were correctly typed. The performance of the parameters was dependent on the obtained classification (i.e., tumor-tumor versus tumor-benign). CONCLUSIONS: Our results suggest that SSA is valuable in the differential classification of mesothelioma and that it supplements a visually appraised diagnosis. The recognition scores may be increased by a combination of SSA with, for example, cellular or nuclear parameters, measured at higher magnifications to form a solid base for fully automated expert systems.
Adenocarcinoma↗
Automated breast tumor diagnosis and grading based on wavelet chromatin texture description.
In this paper, wavelets were employed for multi-scale image analysis to extract parameters for the description of chromatin texture in the cytological diagnosis and grading of invasive breast cancer. Their value was estimated by comparing the performance of co-occurrence, densitometric, and morphometric parameters in an automated K-nearest neighbor (Knn) classification scheme based on light microscopic images of isolated nuclei of paraffin-embedded tissue. This design allowed a multifaceted cytological retrospective study of which the practical value can be judged easily. Results show that wavelets perform excellently with classification scores comparable with densitometric and co-occurrence features. Moreover, because wavelets showed a high additive value with the other textural groups, this panel allowed a very profound description with higher recognition scores than previously reported (76% for individual nuclei, 100% for cases). Morphometric parameters performed less well and only slightly increased correct classification. The major drawback, besides image segmentation errors demanding operator supervision, emanated to be the few false-negative cases, which restrict the immediate practical use. However, an enlargement of the parameter set may avoid this misclassification, resulting in an applicable expert system of practical use.
Automation↗
Botryomycosis mimicking a liposarcoma.
Botryomycosis is an atypical reaction of the host to a common bacterial infection. A case of botryomycosis mimicking a liposarcoma as suspected on clinical and radiological grounds is described. The diagnosis was made by biopsy and culture of the lesion. A review of the literature is given.
Abdomen↗
Cytokeratin profiles and mucin secretion in combined hepatocellular-cholangiocarcinoma. A case report.
A case of a combined hepatocellular-cholangiocarcinoma (HCC-CC) is presented showing mucin production in both the HCC and the CC component. Immunohistochemical staining for cytokeratins 7 and 19 was performed and it is concluded that immunoreactivity for cytokeratin 7 and 19 is an additional criterion to the detection of mucin in making the diagnosis of a combined HCC-CC of the transitional type.
Carcinoma, Hepatocellular↗
Paclitaxel for malignant pleural mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group.
The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m-2 as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and antihistamines. This regimen was well tolerated, with < 4% of cycles resulting in severe toxicity. No major objective responses were observed and ten patients had stable disease. Median survival time was 39 weeks and the 1 year survival rate was 30%. In conclusion, paclitaxel at the dose and schedule investigated in this trial had no major activity in the treatment of malignant pleural mesothelioma.
Adult↗
Histoplasma capsulatum infection in three AIDS patients living in Africa.
Three AIDS patients are reported, 2 European and 1 African. All 3 developed Histoplasma capsulatum infection while living in Africa. Two developed a pulmonary infiltrate, and 2 had skin lesions. One patient was successfully treated with itraconazole, 400 mg daily; in a second patient, itraconazole was partially successful; the third patient was lost to follow-up before adequate treatment could be started. Histoplasma infection is probably an often undiagnosed complication in African AIDS patients.
AIDS-Related Opportunistic Infections↗
A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma.
BACKGROUND: This study investigated the feasibility and efficacy of doxorubicin dose-escalated chemotherapy in combination with ifosfamide in patients with malignant mesothelioma. PATIENTS AND METHODS: In this single institution phase II study, 24 chemotherapy-naive, eligible patients were entered. The chemotherapy regimen consisted of doxorubicin 75 mg/m2 in combination with ifosfamide 5 gr/m2 given as a continuous 24 hour infusion, every 21 days with either rhG-CSF (5 micrograms/kg) or rhGM-CSF (250 micrograms/m2) as haematopoietic support from d3 to d14. Cycles were repeated every 3 weeks. RESULTS: We treated 24 patients, of whom 22 are evaluable for tumour response. One of the two inevaluable patients died from a cerebral haemorrhage during a period of grade III thrombocytopenia after the second course. In 7 patients a partial response was observed, resulting in a response rate of 32% (95% confidence interval 13%-51%). Median response duration was 6 months (range 1-13) and median survival was 7 months (range 1-18). CONCLUSIONS: The high-dose regimen with growth factor support is feasible in this group of patients and leads to an interesting response rate. The limiting toxicity for further dose increments and more courses of treatment, was cumulative thrombocytopenia. There seems to be a subgroup of patients with malignant mesothelioma which is less susceptible to develop thrombocytopenia. However, the overall toxicity and the poor response duration limit the use of this schedule in the treatment of malignant mesothelioma.
Adult↗
Immunoreactivity for the beta chain of the platelet-derived growth factor receptor in malignant mesothelioma and non-neoplastic mesothelium.
The results of an immunohistochemical study of platelet-derived growth factor receptor (PDGF-R) beta chain in human non-neoplastic mesothelium (35 cases) and in malignant mesothelioma (33 cases) using a murine monoclonal antibody are reported. In approximately half of the malignant mesotheliomas, there was immunoreactivity in the cytoplasm of the neoplastic cells for the beta chain of the PDGF-R. In some cases, there was also membrane immunoreactivity. There were no statistically significant differences between the various mesothelioma subtypes. Immunoreactivity for PDGF-R beta chain was absent in non-neoplastic mesothelium.
Animals↗
Immunoreactivity for P-170 glycoprotein in malignant mesothelioma and in non-neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB-1.
The results of an immunohistochemical study of P-170 glycoprotein immunoreactivity in human non-neoplastic mesothelium (35 cases) and in malignant mesothelioma (33 cases) using the murine monoclonal antibody JSB-1 are reported. The majority of malignant mesothelioma cases exhibited cytoplasmic and membrane immunoreactivity in neoplastic cells. These findings are highly significant when compared with the absence of immunoreactivity in normal mesothelium.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium.
The presence of p53 protein in non-neoplastic pleural mesothelium (40 cases) and in human malignant mesothelioma (36 cases) was assessed immunohistochemically using the antibodies DO7, CM-1, and PAb240. In a quarter of the malignant mesotheliomas, there was nuclear immunoreactivity for p53 protein with both the DO7 and CM-1 antibodies. There were no statistically significant differences between the various mesothelioma subtypes (P > 0.05). No immunoreactivity was found with the PAb240 antibody, suggesting absence of mutant-type p53 protein. Nonneoplastic mesothelium was not immunoreactive with any of the antibodies. We conclude that there is immunoreactivity for p53 protein in some mesotheliomas. p53 protein immunoreactivity could be used to discriminate between neoplastic and reactive mesothelium.
Epithelium↗
Persistent diarrhoea in Zairian AIDS patients: an endoscopic and histological study.
To determine the aetiology of persistent diarrhoea in African patients with acquired immunodeficiency syndrome (AIDS), 42 patients with human immunodeficiency virus (HIV) and persistent diarrhoea were enrolled in a microbiological, endoscopic, and histological study. Cryptosporidium was the intestinal parasite most often identified (30%); Isospora belli was found in 12% of the patients. Histological examination of the duodenal mucosa showed a non-specific inflammatory reaction in a significantly higher number of HIV-seropositive patients (82%) than HIV-seronegative controls without diarrhoea (52%) (p = 0.02). Lymphocytes were more likely to be found in inflammatory reactions in HIV-seropositive patients than in controls (p less than 0.0001). Pathogens were observed in histological sections of the duodenum of HIV-seropositive patients only (p = 0.002) and included cryptosporidia (four patients) Isospora belli (one), Strongyloides stercoralis (one), and Cryptococcus neoformans (one). On histological examination the rectal mucosa of HIV-seropositive patients and controls was similar, except eosinophils were more likely to be present in inflammatory reaction in HIV-seropositive patients (p = 0.05) and enteric pathogens were observed only in HIV-seropositive patients (cytomegalovirus inclusion bodies (one) and Schistosoma mansoni (two). The aetiology of persistent diarrhoea in most African AIDS patients remains unclear.
Democratic Republic of the Congo↗
Evidence of functional cellular immune impairment in an adult Belgian with visceral leishmaniasis acquired in Spain.
An adult Belgian patient with visceral leishmaniasis acquired while on holiday in Spain is described. This patient's cellular immunity was assessed by skin testing using six different antigens and was normal just before leaving for Spain. During the leishmaniasis, skin tests with the same antigens showed complete anergy. Lymphocyte transformation tests to antigens and mitogens were severely impaired but normal T cell subsets determined by OKT monoclonal antibodies were found. Immune complexes, containing antibodies to Leishmania antigen were isolated during the patient's illness. It is most likely that visceral leishmaniasis caused the functional cellular immune impairment of the patient.
Antigen-Antibody Complex↗