| 1. |
- Cedervall, Jessica, et al.
(författare)
-
Species-specific in vivo engraftment of the human BL melanoma cell line results in an invasive dedifferentiated phenotype not present in xenografts
- 2009
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:9, s. 3746-3754
-
Tidskriftsartikel (refereegranskat)abstract
- For clinically relevant studies on melanoma progression and invasiveness, in vivo experimental systems with a human cellular microenvironment would be advantageous. We have compared tumor formation from a human cutaneous malignant melanoma cell line (BL), after injection as conventional xenografts in the mouse, or when injected into a predominantly species-specific environment of human embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The resulting melanoma histology was generally analogous, both systems showing delimited densely packed areas with pleomorphic cells of malignant appearance. A specificity of the integration process into the human embryonic teratoma tissues was indicated by the melanoma exclusively being found in areas compatible with condensed mesenchyme, similar to neural crest development. Here, also enhanced neovascularization was seen within the human mesenchymal tissues facing the BL melanoma growth. Furthermore, in the hEST model an additional melanoma cell phenotype occurred, located at the border of, or infiltrating into, the surrounding human loose mesenchymal fibrous stroma. This BL population had a desmoplastic spindle-like appearance, with markers indicative of dedifferentiation and migration. The appearance of this apparently more aggressive phenotype, as well as the induction of human angiogenesis, shows specific interactions with the human embryonic microenvironment in the hEST model. In conclusion, these data provide exciting options for using the hEST model in molecular in vivo studies on differentiation, invasiveness, and malignancy of human melanoma, while analyzing species-specific reactions in vivo.
|
|
| 2. |
- Kasim, Ihsan, et al.
(författare)
-
A recruitment breath manoeuvre directly after endotracheal suction improves lung function : an experimental study in pigs
- 2009
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 114:3, s. 129-135
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atelectasis occurs after a well performed endotracheal suction. Clinical studies have shown that recruitment manoeuvres added after endotracheal suction during mechanical ventilation restore lung function. Repetitive lung over-distension is, however, harmful for the lung, and the effects of adding a larger breath, recruitment breath, directly after repeated endotracheal suction were therefore investigated.METHODS: Twelve healthy anaesthetized pigs were randomized into two groups: one without and one with a recruitment breath manoeuvre (RBM), i.e. a breath 15 cmH(2)O above inspiratory pressure for 10 s during pressure-controlled ventilation. The pigs were suctioned every hour for 4 hours with an open suction system.RESULTS: At the end of the study there was a statistically significant difference between the group given RBM and that without with respect to PaCO(2), tidal volume (V(T)), and compliance (Crs). Without RBM, the PaCO(2) increased from 4.6+/-0.4 to 6.1+/-1.5 kPa, V(T) decreased from 345+/-39 to 247+/-71 mL, and Crs decreased from 28+/-6 to 18+/-5 mL/cmH(2)O. There was no change in PaCO(2) or Crs when a RBM was given. Morphological analysis revealed no differences in aeration of apical and central lung parenchyma. In the basal lung parenchyma there were, however, greater areas with normal lung parenchyma and less atelectasis after RBM.CONCLUSIONS: Atelectasis created by endotracheal suction can be opened by inflating the lung for a short duration with low pressure, without over-distension, immediately after suction.
|
|
| 3. |
- Sun, Xiaojuan, et al.
(författare)
-
Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells
- 2006
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 232:2, s. 161-169
-
Tidskriftsartikel (refereegranskat)abstract
- Malignant mesothelioma is an increasingly common tumor with an almost 100% mortality rate. It is refractory to conventional treatment. We have previously shown with SSH and microarray that the mRNA expression level of proteasome is higher in epithelioid mesothelioma cell lines than in sarcomatoid ones. This study evaluates the differential apoptotic effect of proteasome inhibitors on both of these mesothelioma sub-lines. Proteasome inhibitors show substantial anti-tumor activity in some tumor cells in vitro and in vivo, but the effects on mesothelioma cells has not been studied. The viability of mesothelioma cells was reduced in a dose- and time-dependent manner by the proteasome inhibitors tested; PSI was effective with a low dose, but higher concentrations were needed for calpain inhibitor I. The epithelioid mesothelioma cells are more sensitive to the inhibitors than the sarcomatoid ones, their IC50 after 24 h of treatment with PSI being 4 and 16 microm, respectively. Other mesothelioma cell lines show similar sensitivity. PSI seemed to decrease mesothelioma viability by inducing apoptosis, as verified by cell morphology, Western blotting analysis of caspase 3 cleavage, and flow-cytometric analysis. In conclusion, PSI, a representative agent that reduces viability and induces apoptosis of mesothelioma cells, might be useful in the treatment of patients with mesothelioma, especially of epithelioid phenotype.
|
|
