Surgical stress and accelerated tumor growth

Background: Delay in the initiation of radiotherapy after surgery is associated with an increase in local regional recurrence. A possible mechanism might be that remaining tumor cells proliferate significantly faster as a result of induced angiogenic cytokines. The growth rate of tumors arising from the inoculation of L44 tumor cells in the wound bed after surgical removal of L44 tumors was determined. Materials and Methods: L44 tumors growing in the flank of female BN rats were surgically removed. In the wound. bed, 5x10(6) L44 cells, harvested from the in vitro cell line, were injected. L44 cells were also injected in the contralateral flank and in control rats with and without surgical intervention. Tumor volumes as a function of time after injection of cells were recorded. From the attained volume at day 7, the cell doubling time was calculated, assuming 109 cells per cm Results: Tumors arising in the wound bed had the fastest growth rate as compared to the tumors in the contralateral flank or tumors in control rats with or without surgical intervention. Conclusion: The results clearly indicate accelerated tumor growth after surgical stress. This indicates that delay in the initiation of radiotherapy after surgery with tumor cells remaining, results in a larger tumor burden and hence a higher probability of local recurrence.</p

Surgical stress and accelerated tumor growth

Background: Delay in the initiation of radiotherapy after surgery is associated with an increase in local regional recurrence. A possible mechanism might be that remaining tumor cells proliferate significantly faster as a result of induced angiogenic cytokines. The growth rate of tumors arising from the inoculation of L44 tumor cells in the wound bed after surgical removal of L44 tumors was determined. Materials and Methods: L44 tumors growing in the flank of female BN rats were surgically removed. In the wound. bed, 5x10(6) L44 cells, harvested from the in vitro cell line, were injected. L44 cells were also injected in the contralateral flank and in control rats with and without surgical intervention. Tumor volumes as a function of time after injection of cells were recorded. From the attained volume at day 7, the cell doubling time was calculated, assuming 109 cells per cm Results: Tumors arising in the wound bed had the fastest growth rate as compared to the tumors in the contralateral flank or tumors in control rats with or without surgical intervention. Conclusion: The results clearly indicate accelerated tumor growth after surgical stress. This indicates that delay in the initiation of radiotherapy after surgery with tumor cells remaining, results in a larger tumor burden and hence a higher probability of local recurrence

Tumor drug distribution after local drug delivery by hyperthermia, in vivo

Tumor drug distribution and concentration are important factors for effective tumor treatment. A promising method to enhance the distribution and the concentration of the drug in the tumor is to encapsulate the drug in a temperature sensitive liposome. The aim of this study was to investigate the tumor drug distribution after treatment with various injected doses of different liposomal formulations of doxorubicin, ThermoDox (temperature sensitive liposomes) and DOXIL (non-temperature sensitive liposomes), and free doxorubicin at macroscopic and microscopic levels. Only ThermoDox treatment was combined with hyperthermia. Experiments were performed in mice bearing a human fibrosarcoma. At low and intermediate doses, the largest growth delay was obtained with ThermoDox, and at the largest dose, the largest growth delay was obtained with DOXIL. On histology, tumor areas with increased doxorubicin concentration correlated with decreased cell proliferation, and substantial variations in doxorubicin heterogeneity were observed. ThermoDox treatment resulted in higher tissue drug levels than DOXIL and free doxorubicin for the same dose. A relation with the distance to the vasculature was shown, but vessel perfusion was not always sufficient to determine doxorubicin delivery. Our results indicate that tumor drug distribution is an important factor for effective tumor treatment and that its dependence on delivery formulation merits further systemic investigation

Evidence of cartilage repair by joint distraction in a canine model of osteoarthritis

Objective. Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage, bone, and synovial tissue changes that lead to pain and functional impairment. Joint distraction is a treatment that provides long-term improvement in pain and function accompanied by cartilage repair, as evaluated indirectly by imaging studies and measurement of biochemical markers. The purpose of this study was to evaluate cartilage tissue repair directly by histologic and biochemical assessments after joint distraction treatment. Methods. In 27 dogs, OA was induced in the right knee joint (groove model; surgical damage to the femoral cartilage). After 10 weeks of OA development, the animals were randomized to 1 of 3 groups. Two groups were fitted with an external fixator, which they wore for a subsequent 10 weeks (one group with and one without joint distraction), and the third group had no external fixation (OA control group). Pain/function was studied by force plate analysis. Cartilage integrity and chondrocyte activity of the surgically untouched tibial plateaus were analyzed 25 weeks after removal of the fixator. Results. Changes in force plate analysis values between the different treatment groups were not conclusive. Features of OA were present in the OA control group, in contrast to the generally less severe damage after joint distraction. Those treated with joint distraction had lower macroscopic and histologic damage scores, higher proteoglycan content, better retention of newly formed proteoglycans, and less collagen damage. In the fixator group without distraction, similarly diminished joint damage was found, although it was less pronounced. Conclusion. Joint distraction as a treatment of experimentally induced OA results in cartilage repair activity, which corroborates the structural observations of cartilage repair indicated by surrogate markers in humans

DCE-MRI and IVIM-MRI of rabbit Vx2 tumors treated with MR-HIFU-induced mild hyperthermia

BACKGROUND: The purpose of this study is to investigate whether changes could be detected in dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR parameters upon MR-guided high-intensity focused ultrasound (MR-HIFU)-induced hyperthermia in a rabbit Vx2 tumor model. METHODS: Five Vx2 tumor-bearing New Zealand white rabbits were treated with hyperthermia using a clinical MR-HIFU system. Data were acquired before and after hyperthermia. For the DCE analysis, the extended Tofts model was used. For the IVIM analysis, a Bayesian approach was used. Maps were reconstructed of the DCE parameters (K (trans), k ep, and v p ) and IVIM parameters (D t , f p , and D p ). Individual parameter histograms and two-dimensional cross-correlation histograms were constructed to analyze changes in the parameters after hyperthermia. Changes in median values were tested for statistical significance with the Mann-Whitney U test. RESULTS: The MR temperature measurements confirmed that mild hyperthermia (40 to 42 °C) was successfully achieved in all rabbits. One rabbit died during treatment and was excluded from the analysis. In the remaining four rabbits, an increase in D t was observed. In three rabbits, an increase in K (trans) was observed, while in the other rabbits, all three DCE parameter values decreased. Mixed changes were seen for v p and f p . CONCLUSIONS: Changes in DCE and IVIM parameters were detected after hyperthermia and were variable between the rabbits. DCE- and IVIM-MRI may be promising tools to assess tumor responses to hyperthermia. Further research in a larger number of subjects is necessary in order to assess their value for treatment response monitoring

T₁ and T₂* in the microsphere pellet and supernatant of alginate microspheres before and after mild hyperthermia.

<p>T₁ in the microsphere pellet (A) and supernatant (B) and T₂* in the microsphere pellet (C) of alginate microspheres before and after mild hyperthermia (HT; 42°C for 15 minutes). A region of interested (ROI) was positioned in the microsphere pellet (if present) or the supernatant to determine the T₁ and T₂*-values (Mean + standard deviation).</p

Temperature triggered release of DOX from TSL.

<p>Temperature triggered release of DOX from TSL (DPPC:MSPC:DSPE-PEG2.000 86:10:4) in 20 mM HEPES buffer pH 7.4 (A) or 50% fetal bovine serum (B) at 37 and 42°C. Temperature triggered DOX release from TSL-Ba-ms in 20 mM HEPES buffer pH 7.4 (C) and 50% FBS (D) at 37 and 42°C.</p

Characteristics of temperature senstitive liposomes (TSL) loaded with DOX and [Gd(HPDO3A)(H₂O)].

<p>Characteristics of temperature senstitive liposomes (TSL) loaded with DOX and [Gd(HPDO3A)(H₂O)].</p