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Biomedical subjects

D Molin

Publications and source records attributed to D Molin.

8 recordsLinked to original sources

Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is characterised by an unbalanced cytokine secretion. Many of these cytokines have been implicated in the regulation of malignant and infiltrating cells. Interleukin-9 (IL-9) has been described to act in an autocrine fashion in HL, stimulating proliferation of the malignant cells. To investigate the potential clinical implication of this observation, a novel ELISA method was used to examine the serum levels of IL-9 in lymphoma patients. High levels of IL-9 were found in the sera from patients with HL (18/44), but not in the sera from non-Hodgkin's lymphoma patients (3/21) or healthy controls. The highest serum IL-9 levels, up to 3350 pg/ml, were observed in the nodular sclerosis subtype, and there was a correlation between IL-9 levels and the negative prognostic factors advanced stage, B-symptoms, low blood Hb and high erythrocyte sedimentation rate. Furthermore, there was no correlation between serum levels of IL-9 and IL-13, a cytokine where serum levels have been speculated to be of clinical importance. This is the first report showing that IL-9 can be measured in serum samples. A novel correlation between increased serum IL-9 levels, HL and clinical features is shown, suggesting that IL-9 is a candidate factor contributing to the development of HL.

Biomarkers, Tumor↗

Tumour markers as early predictors of response to chemotherapy in advanced colorectal carcinoma.

BACKGROUND: To evaluate the reliability and validity of serum carcinoembryonic antigen (CEA), tissue polypeptide-specific antigen (TPS), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in monitoring palliative chemotherapy in advanced colorectal cancer (ACRC). METHODS: Serum was prospectively collected from 87 patients with ACRC treated with first-line 5-fluorouracil and leucovorin before and 2, 4 and 10 weeks after induction. RESULTS: Eight patients had normal baseline TPS levels, and these patients had a favourable outcome with prolonged survival and a higher rate of objective responses than patients with elevated TPS levels. At 10 weeks, all responders had a decreasing TPS value. The sensitivity for a decrease of >25% using TPS was 83% and 86% for objective and subjective responses, respectively, and the specificity was 65% and 72%, respectively. CEA had, in the same setting, a sensitivity of 45% and 46%, respectively, and the specificity was 88%. VEGF was elevated in 54% of the patients and bFGF in 15% of the patients. The VEGF values decreased during therapy in 94% of the patients, but the changes in serial VEGF values did not correlate with survival or response. Tumour markers used together did not enhance the predictive values of TPS alone. CONCLUSIONS: Repeated measurements of CEA, VEGF and bFGF in serum are of limited value in monitoring chemotherapy in ACRC. TPS seems to be of greater interest, but does not predict exactly which patients are going to have a positive outcome of palliative chemotherapy.

Adenocarcinoma↗

Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease.

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Adult↗

The serum levels of eosinophil cationic protein (ECP) are related to the infiltration of eosinophils in the tumours of patients with Hodgkin's disease.

We have previously described a relation between abundance of eosinophilic granulocytes in Hodgkin's disease (HD) tumours and poor prognosis. In order to further explore the importance of the eosinophilic infiltration, we immunohistochemically examined the presence of eosinophils, using the monoclonal antibodies EG 1 and EG 2, in the tumours of 54 newly diagnosed patients with HD and related the degree of infiltration to clinical characteristics and the serum levels of eosinophil cationic protein (S-ECP). S-ECP levels (upper normal value 16 micrograms/l) varied between 2.2 and 71.7 micrograms/l, mean 25.4 micrograms/l. There was an association (p = 0.01) between the number of eosinophils in the tumour tissue and S-ECP. S-ECP levels were also associated to high erythrocyte sedimentation rate (ESR, p < 0.01) and nodular sclerosis (NS) histology (p < 0.05), and there was a tendency of a correlation to bulky disease (p = 0.06). The number of eosinophils stained with EG 2 correlated to high ESR (p < 0.05), and to high leukocyte count (p = 0.02). A follow-up value of S-ECP after treatment was, in most of the cases measured, lower than the initial value. The high values of S-ECP in several patients with HD probably originates from eosinophils infiltrating the tumours. The same patients had a higher ESR and tended to have a more advanced stage and bulky disease. There are no significant correlations with disease-free and overall survival, as the follow-up time is short, and prognosis favourable.

Adolescent↗

Apoptosis in cardiac development.

Cell degeneration, as a phenomenon accompanying developmental processes, was originally described over a century ago. Apoptosis, a term introduced approximately three decades ago, has occupied investigators particularly with respect to cell and tissue kinetics, emphasizing its role in the disposal of supernumerary, malinstructed or damaged cells. Although apoptosis is mostly related to developmental processes, evidence has been gathered indicating that it may also perform other roles. In this review, which concentrates on cardiac development, we examine focal apoptosis and subsequent signal cascades in combination with timed morphogenetic events. Apoptosis mainly occurs in the non-myocardial compartment of the embryonic heart, a compartment that consists of cells derived from the endocardium, the epicardium and the neural crest. The last-mentioned population invades the outflow tract and the atrioventricular endocardial cushions. The signalling cascade seems to involve the activation of latent transforming growth factor beta, resulting in cardiomyocyte migration and subsequent myocardialization of the endocardial cushions. Aberrant apoptosis accompanies cardiac anomalies. Furthermore, an apoptotic population is found surrounding the developing conduction system. A possible role for differentiation is suggested.

Animals↗

Respiratory behavior in groups of deaf and non-deaf GFF male mice.

Carbon dioxide emission (VCO2) of groups of 10 GFF mice, genetically deaf and non-deaf, were compared, in controlled conditions of temperature 20-21 degrees C, humidity 50-80% and light (LD12:12; L = 108 lux). A circadian rhythm of VCO2 was evidenced in both genotypes, with levels in D and in L significantly (0.001 less than p less than 0.01) greater in deaf than in non-deaf mice. Photic VCO2 variations were significantly (0.001 less than p less than 0.05) smaller at L----D and D----L in the deaf than in non-deaf genotype. Ultradian (tau greater than 20 minutes) rhythms were evidenced in both genotypes; Fourier periodic analysis showed several significant (0.001 less than p less than 0.05) differences between these 2 genotypes concerning mainly amplitudes, whilst spectral analysis showed slight frequency differences between them. Survival to an acute nitrogen hypoxia or to an acute carbon monoxide intoxication which was significantly (p less than 0.001 and p less than 0.05) lower in deaf than in non-deaf individuals confirms the differences in respiratory behavior of groups of these two strains of mice.

Acoustic Stimulation↗

Respiratory activity variations induced in groups of LD 12:12 synchronized Sprague-Dawley rats by a 100 dB white noise emitted at 12-h intervals.

A white noise is emitted during 2 h, either in the middle of the scotoperiod (activity period) or of the photoperiod (rest period), on grouped specific pathogen free (SPF) male Sprague-Dawley rats, LD 12:12 synchronized by light (L = 6 h = 150 lux). Continuous measurements of VCO2, taken as an index of respiratory activity shows: 1. a short increase both after the beginning and the end of the stimulus, with slight time length differences between young and older rats; 2. a slight (2-3%) continued increase during the photoperiod and a high decrease (13%) during the scotoperiod. These VCO2 variations obtained during and after the white noise emission correspond to measurements of activity displacement and observations of behavior performed on a small sample of rats.

Age Factors↗