Biomedical subjects

M Dellian

Publications and source records attributed to M Dellian.

40 records · Page 3Linked to original sources

PubMed1992

Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3.

BACKGROUND: Some studies suggest that nutritional blood flow and intratumor levels of high-energy phosphates such as adenosine triphosphate (ATP) affect tumor response to treatment. Reports of intratumor variabilities have shown that distribution of high-energy phosphates within experimental and human tumors is not uniform, and this variability may be related to differences in blood flow in different regions of the tumor. However, previous studies provide no insight into the intratumor relationship of these parameters. PURPOSE: To study the intratumor relationship between blood flow and ATP concentration, we have developed a method that allows simultaneous quantitation of the two variables almost at a cellular level at adjacent sites. In addition, this technique, which uses digital image processing and analysis, facilitates regional high-resolution measurements of blood flow and ATP concentrations in relation to histology. METHODS: We examined tissue samples cut in consecutive order from one representative hamster A-Mel-3 amelanotic melanoma. Specimens from the same tumor were analyzed for histological features, blood flow (measured autoradiographically by the use of [4-N-methyl-14C]iodoantipyrine), and ATP content (measured by a quantitative substrate-induced bioluminescence reaction, using single-photon imaging). The data on the three parameters were stored as digitized images, which were later transformed to reach geometric congruency. The relationship between blood flow and ATP was examined by nonlinear regression and correlation analyses. RESULTS: Regional distribution of blood flow was highly correlated with distribution of ATP within the A-Mel-3 tumor. For images of the tumor using measuring fields of approximately 20 tumor cells, the coefficient of correlation was .92 (P < .001). The relationship between the two parameters was described by a second-order function. At low blood flow values, small differences in blood flow were associated with large changes in levels of ATP, whereas at high blood flow values, differences in blood flow were associated with much smaller changes in ATP levels. CONCLUSION: This high-resolution technique may have applications in future studies investigating the relationship between tumor cell metabolism and regional blood flow and in studies aimed at identifying the locoregional target of various cancer therapies.

Adenosine Triphosphate↗

PubMed1992

Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response.

Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to find out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100-150 mm3. Hyperthermia was induced by immersing the tumor in a water bath at 43 degrees C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P less than 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P less than 0.05 versus 43 degrees C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43 degrees C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy.

Animals↗

PubMed1992

Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours.

Iodo(14C-)antipyrine autoradiography and imaging bioluminescence have been combined to obtain pixel-to-pixel correlations between absolute values for local blood flow and ATP concentrations at a microscopical level within designated areas in hamster melanomas. Positive pixel-to-pixel correlations were obtained in 4 of 6 tumours. Both flow and ATP values were less in mostly necrotic than in mostly viable tumour regions. The data provide evidence for the energetic state of cancer cells being strongly influenced by the efficiency of tumour microcirculation in several but not in all malignancies investigated.

Adenosine Triphosphate↗

PubMedDate not supplied

Tissue distribution and penetration of 5-ALA induced fluorescence in an amelanotic melanoma after topical application.

BACKGROUND: Photodynamic therapy (PDT) following topical application of 5-aminolevulinic acid (ALA) is increasingly employed for several types of malignancies. However, data with respect to tissue penetration and distribution of ALA-induced porphyrins after topical application are scarce. Therefore, it was our aim to study tissue distribution and the penetration potency of topically applied ALA. MATERIAL AND METHODS: We used Syrian golden hamsters implanted with the amelanotic melanoma A-Mel-3 growing in a transparent dorsal skinfold chamber. ALA was topically applied in aqueous solution at a concentration of 3% for 4 hours. The fluorescence pattern was quantified by fluorescence microscopy and digital image analysis from cryosections and given as percentage of a reference standard in medians (25%, 75% quartiles). RESULTS: Fluorescence intensities in tumors were 90.8% (56.2%, 115.2% of a reference standard, p < 0.01 vs. normal tissue) significantly exceeding normal surrounding host tissue yielding fluorescence intensities of 12.1% (9.1%, 16.1%). The tumor selectivity, that is the ratio of fluorescence intensities between tumor and normal tissue, was 7.3 (6.1, 9.1). For superficial tumors with a thickness of approximately 1 mm no fluorescence gradients after topical application of ALA could be observed. CONCLUSION: In superficial cancerous lesions the fluorescence distribution of ALA induced porphyrins is tumor selective without significant fluorescence gradients throughout the tumor. Thus, by optimising the treatment modalities for topical ALA-PDT an enhanced efficacy and selectivity will be reached.

Administration, Topical↗