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1.
AIM: To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux. METHODS AND MATERIALS: Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1 and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each.RESULTS: Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing. CONCLUSIONS: A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.  相似文献   

2.
Both host carbogen (95% oxygen/5% carbon dioxide) breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the effects of nicotinamide alone and in combination with host carbogen breathing on transplanted rat GH3 prolactinomas. Gradient recalled echo (GRE) MRI, sensitive to blood oxygenation changes, and spin echo (SE) MRI, sensitive to perfusion/flow, showed large signal intensity increases with carbogen breathing. Nicotinamide, thought to act by suppressing the transient closure of small blood vessels that cause intermittent tumour hypoxia, induced a small increase in blood oxygenation but no detectable change in perfusion/flow. Carbogen combined with nicotinamide was no more effective than carbogen alone. Both carbogen and nicotinamide caused significant increases in the nucleoside triphosphate/inorganic phosphate (betaNTP/Pi) ratio, implying that the tumour cells normally receive sub-optimal substrate supply, and is consistent with either increased glycolysis and/or a switch to more oxidative metabolism. The most striking observation was the marked increase in blood glucose (twofold) induced by both nicotinamide and carbogen. Whether this may play a role in tumour radiosensitivity has yet to be determined.  相似文献   

3.
Purpose: To examine the hypothesis that elevated interstitial fluid pressure (IFP) is a cause of reduced blood flow in tumors.

Materials and Methods: A physiologic model of tumor blood flow was developed based on a semipermeable, compliant capillary in the center of a spherical tumor. The model incorporates the interaction between the tumor vasculature and the interstitium, as mediated by IFP. It also incorporates the dynamic behavior of the capillary wall in response to changes in transmural pressure, and the effect of viscosity on blood flow.

Results: The model predicted elevated tumor IFP in the range of 0 to 56 mmHg. The capillary diameter in the setting of elevated IFP was greatest at the arterial end, and constricted to between 3.2 and 4.4 μm at the venous end. This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of the capillary. The IFP exceeded the intravascular pressure distally in the capillary, but vascular collapse did not occur. Capillary diameter constriction resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow relative to a state of near-zero IFP.

Conclusion: The results suggest that steady-state vascular constriction occurs in the setting of elevated IFP, and leads to reduced tumor blood flow. This may in turn contribute to the development of hypoxia, which is an important cause of radiation treatment failure in many tumors.  相似文献   


4.
Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether chronic or acute changes in tumour perfusion necessarily lead to changes in tissue oxygenation and bioenergetic status since, as a rule, blood flow is thought to be the ultimate determinant of the tumour bioenergetic status. Based on this study, there is clear experimental evidence that growth-related or acute (following i.v. administration of tumour necrosis factor alpha) decreases in tumour blood flow are accompanied by parallel alterations in tissue oxygenation. In contrast, tumour energy status remains stable as long as flow values do not fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the main substrate can be recruited from the enlarged interstitial compartment. Perfusion rate seems to play a paramount role in determining energy status only in low-flow tumours or low-flow tissue areas.  相似文献   

5.
PURPOSE: Evaluation of vascular disruptive activity in orthotopic models as potential surrogate biomarkers of tumor response to the microtubule-stabilizing agent patupilone. EXPERIMENTAL DESIGN: Mice bearing metastatic B16/BL6 melanoma and rats bearing mammary BN472 tumors received vehicle or efficacious patupilone doses (4 and 0.8-1.5 mg/kg i.v., respectively). Tumor vascularity assessment by dynamic contrast-enhanced or dynamic susceptibility contrast magnetic resonance imaging and interstitial fluid pressure (IFP) occurred at baseline, 2 days (mice and rats), and 6 days (rats) after treatment and were compared with histologic measurements and correlated with tumor response. RESULTS: In B16/BL6 metastases, patupilone (4 mg/kg) induced a 21 +/- 5% decrease (P < 0.001) in tumor blood volume and a 32 +/- 15% decrease (P = 0.02) in IFP after 2 days and reduced tumor growth and vessel density (>42%) after 2 weeks (P < or = 0.014). Patupilone dose-dependently inhibited BN472 tumor growth (day 6) and reduced IFP on days 2 and 6 (-21% to -70%), and the percentage change in IFP correlated (P < 0.01) with the change in tumor volume. In both models, histology and vascular casts confirmed decreases in tumor blood volume. One patupilone (0.8 mg/kg) administration decreased (P < 0.01) tumor IFP (54 +/- 4%), tumor blood volume (50 +/- 6%), and vessel diameter (40 +/- 11%) by day 6 but not the apparent diffusion coefficient, whereas histology showed that apoptosis was increased 2.4-fold and necrosis was unchanged. Apoptosis correlated negatively (P < 0.001) with IFP, tumor blood volume, and tumor volume, whereas tumor blood volume and IFP were correlated positively (P = 0.0005). CONCLUSIONS: Vascular disruptive effects of patupilone were detected in situ using dynamic contrast-enhanced or dynamic susceptibility contrast magnetic resonance imaging and IFP. Changes in IFP preceded and correlated with tumor response, suggesting that IFP may be a surrogate biomarker for patupilone efficacy.  相似文献   

6.
PURPOSE: Experiments were conducted to elucidate the relationship between the changes in oxygen partial pressure (pO2) and blood flow in heated tumors with an ultimate goal of using mild temperature hyperthermia (MTH) to increase tumor oxygenation. METHODS AND MATERIALS: The blood flow and pO2 in the R3230 adenocarcinoma grown (subcutaneously) in the right hind limbs of Fischer rats were measured immediately or 24 h after heating at 40.5 degrees-43.5 degrees C for 30 or 60 min. The blood flow was measured with the radioactive microsphere method and the tumor pO2 was measured polarographically using an Eppendorf pO2 histograph. RESULTS: The tumor PO2 significantly increased immediately and 24 h after heating for 30 min at 40.5 degrees-43.5 degrees C or for 60 min at 40.5 degrees and 41.5 degrees C. On the other hand, in tumors heated at 42.5 degrees C for 60 min, the tumor pO2 immediately after heating was similar to the control value whereas that 24 h after heating was about threefold greater than the control tumor pO2. Heating at 43.5 degrees C for 60 min resulted in a significant decline in pO2 immediately after and 24 h after heating. The increase in tumor pO2 immediately after heating appeared to be due to an increase in tumor blood flow. However, the changes in tumor pO2 and tumor blood flow 24 h after heating, particularly after high thermal doses (e.g., 60 min heating at 42.5 degrees or 43.5 degrees C), were not correlated. CONCLUSION: Heating at mild temperatures (i.e., 40.5 degrees-42.5 degrees C for 30-60 min), caused thermal dose-dependent increases in pO2 in the R3230 AC tumors of Fischer rats during 0-24 h after heating. Such an increase in tumor oxygenation after MTH appeared to be due to an increase in tumor blood flow.  相似文献   

7.
Interstitial fluid pressure was measured by the wick-in-needle technique in DMBA-induced rat mammary tumours during resting conditions and during noradrenaline infusion. The rate of infusion was chosen to increase the systemic blood pressure by 30-40 mmHg, known to result in a markedly increased vascular resistance of these tumours. During resting conditions tumour interstitial fluid pressure was 10.3 +/- 1.3 mmHg (n = 13) but fell to 7.0 +/- 1.1 mmHg (n = 13) during noradrenaline infusion. The results suggests that noradrenaline is likely to affect the pre-capillary resistance vessels of the tumour vascular bed. This result, together with earlier perfusion studies, indicates that noradrenaline is unsuitable for increasing tumour cell perfusion as an adjunctive in radiation and cytotoxic drug therapy.  相似文献   

8.
Elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors. The etiology of tumor interstitial hypertension is poorly understood. We have postulated that the solid stress generated by tumor cells growing in a confined space compresses blood vessels and increases tumor microvascular pressure and IFP. To test the hypothesis that neoplastic cell loss would decompress blood vessels and lower IFP, we induced apoptosis in tumors with paclitaxel and docetaxel. Taxanes inhibited the growth of the murine mammary carcinoma (MCa-IV) and of the human soft tissue sarcoma (HSTS-26T). Taxanes induced apoptosis and reduced the density of intact neoplastic cells in both MCa-IV and HSTS-26T. To determine whether neoplastic cell loss decompressed blood vessels, we measured the diameter of tumor vessels in HSTS-26T tumors implanted in transparent dorsal skin fold chambers. At 48 and 96 h after paclitaxel, the diameter of tumor vessels was significantly increased. The increase in vascular diameters was associated with reductions in microvascular pressure and IFP. The changes in neoplastic cell density and IFP were also correlated. In the human glioblastoma U87, which is resistant to paclitaxel, the IFP and cellular density were not modified by paclitaxel treatment. Collectively, these results support the hypothesis that solid stress generated by neoplastic cell proliferation increases vascular resistance and IFP. The increase in vessel diameter induced by paclitaxel and docetaxel suggests that taxanes could improve tumor response by increasing the vascular surface area for delivery of therapeutic agents.  相似文献   

9.
PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.  相似文献   

10.
The uptake of therapeutic macromolecules in solid tumours is assumed to be hindered by the heterogeneous vascular network, the high interstitial fluid pressure, and the extracellular matrix. To study the impact of these factors, we measured the uptake of fluorochrome-labelled IgG using confocal laser scanning microscopy, interstitial fluid pressure by the 'wick-in-needle' technique, vascular structure by stereological analysis, and the content of the extracellular matrix constituents collagen, sulfated glycosaminoglycans and hyaluronan by colourimetric assays. The impact of the microenvironment on these factors was studied using osteosarcomas implanted either subcutaneously or orthotopically around the femur in athymic mice. The uptake of IgG was found to correlate inversely with the interstitial fluid pressure and the tumour volume in orthotopic, but not subcutaneous tumours. No correlation was found between IgG uptake and the level of any of the extracellular matrix constituents. The content of both collagen and glycosaminoglycans depended on the site of tumour growth. The orthotopic tumours had a higher vascular density than the subcutaneous tumours, as the vascular surface and length were 2-3-fold higher. The data indicate that the interstitial fluid pressure is a dominant factor in controlling the uptake of macromolecules in solid tumours; and the site of tumour growth is important for the uptake of macromolecules in small tumours, extracellular matrix content and vascularization.  相似文献   

11.
The interstitial fluid pressure (IFP) and the proton spin-lattice and spin-spin relaxation times (T1 and T2) of some experimental tumours have been shown to be related to tumour water content. These observations have led to the hypothesis that magnetic resonance imaging (MRI) might be a clinically useful non-invasive method for assessment of tumour IFP. The purpose of the work reported here was to examine the general validity of this hypothesis. R-18 human melanoma xenografts grown intradermally in Balb/c nu/nu mice were used as the tumour model system. Median T1 and T2 were determined by spin-echo MRI using a 1.5-T clinical whole-body tomograph. IFP was measured using the wick-in-needle technique. No correlation was found between tumour IFP and fractional tumour water content. Moreover, there was no correlation between median T1 or T2 and IFP, suggesting that proton T1 and T2 values determined by MRI cannot be used clinically to assess tumour IFP and thereby to predict the uptake of macromolecular therapeutic agents.  相似文献   

12.
Tumour oxygenation was measured in seven canine soft tissue sarcomas being treated with a fractionated course of radiation and hyperthermia. Measurements obtained during treatment were compared to pre-treatment measurements. The most important finding was an increase in oxygenation in tumours with low pre-treatment oxygenation that persisted throughout treatment. This is an advantageous hyperthermia effect as it may lead to increased radiation cell killing at each fraction. In other tumours, potentially less advantageous changes in oxygenation may be hyperthermia fractionation related and this deserves further investigation.  相似文献   

13.
在多种细胞因子作用下,肿瘤组织间液压(IFP)增高.其对肿瘤的早期诊断、病情进展、预后生存有一定的指示作用,特别是对于患者治疗方案的选择及疗效有较大的指导、预测作用.针对肿瘤组织间液压增高机制的靶向性治疗,极大地提高了肿瘤的疗效.  相似文献   

14.
Elevated intratumoral interstitial fluid pressure (IFP) and tumour hypoxia are independent predictive factors for poor survival and poor treatment response in cancer patients. However, the relationship between IFP and tumour hypoxia has not yet been clearly established. Preclinical studies have shown that lowering IFP improves treatment response to cytotoxic therapy. Interstitial fluid pressure can be reduced by inhibition of phosphorylated platelet-derived growth factor receptor-beta (p-PDGFR-beta), a tyrosine kinase receptor frequently overexpressed in cancer stroma, and/or by inhibition of VEGF, a growth factor commonly overexpressed in tumours overexpressing p-PDGFR-beta. We hypothesised that Imatinib, a specific PDGFR-beta inhibitor will, in addition to p-PDGFR-beta inhibition, downregulate VEGF, decrease IFP and improve tumour oxygenation. A549 human lung adenocarcinoma xenografts overexpressing PDGFR-beta were grown in nude mice. Tumour-bearing animals were randomised to control and treatment groups (Imatinib 50 mg kg(-1) via gavage for 4 days). Interstitial fluid pressure was measured in both groups before and after treatment. EF5, a hypoxia marker, was administered 3 h before being killed. Tumours were sectioned and stained for p-PDGFR-beta, VEGF and EF5 binding. Stained sections were viewed with a fluorescence microscope and image analysis was performed. Imatinib treatment resulted in significant reduction of p-PDGFR-beta, VEGF and IFP. Tumour oxygenation was also significantly improved. This study shows that p-PDGFR-beta-overexpressing tumours can be effectively treated with Imatinib to decrease tumour IFP. Importantly, this is the first study demonstrating that Imatinib treatment improves tumour oxygenation and downregulates tumour VEGF expression.  相似文献   

15.
Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T(1)-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 x 250 microm(2). Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future.  相似文献   

16.
The chronobiology of various physiological phenomena that impact tumour drug delivery has not been established. Since the delivery of therapeutic agents is directly influenced in part by tumour vascular volume (VV), vascular permeability (VP) and local blood flow (BF), we have performed a series of studies to assess the natural rhythms of these functions in tumour and normal tissues. Preliminary results by Hori et al. Cancer Res 1992, 52, 912-916, have demonstrated fluctuations in tumour blood flow in subcutaneous (s.c.) rat tumours with a higher rate at 15-21 h after light onset (HALO) compared with 3-9 HALO. We used the GW-39 and LS174T human colon carcinoma xenografts grown s.c. in nude mice for these studies. VV, VP and BF were determined at 3, 7, 10, 13, 17, 20 and 23 HALO. In separate studies, dosing with a small therapeutic agent ([3H]-5-fluorouracil (5-FU)) or a macromolecule ([131I]-131-MN-14-anti carcinoembryonic antigen (CEA) immunoglobulin G (IgG)) was done at 10 and 17 HALO and 3, 10 and 17 HALO, respectively, and tissue and tumour uptake was determined in each group. Well-defined peaks and nadirs were observed for all three vascular functions. The peaks for VV and VP were similar in tumour and normal tissue whereas BF rate had a unique rhythm in tumour. Using cosinor analysis of the BF rate, we have found that the acrophase (peak) for tumour BF occurs at approximately 17 HALO in both tumour xenografts, while maximal liver, lung and kidney BF occurred at 10-13 HALO. Tumour BF rate ranged from the lowest value of 1.34+/-0.54 microliter/g/min at 20 HALO to the highest value of 2.79+/-0.57 microliter/g/min at 17 HALO. Liver BF rate ranged from 4.1+/-1.1 microliter/g/min at 3 HALO to 10.22+/-1.31 microliter/g/min at 10 HALO, and was 5.83+/-1.37 microliter/g/min at 17 HALO. Thus, the rhythm of tumour and normal tissue BF are different, creating a window of opportunity when tumours can be targeted with a therapeutic agent. At 3 h postinjection, the %ID/g of 5-FU in tumour at 10 HALO was 0.14+/-0.09 and at 17 HALO was 0.32+/-0.12 (P<0.02). In liver at 10 HALO, uptake was 0.13+/-0.06 and at 17 HALO was 0. 07+/-0.03 (P<0.05). At 24 h postinjection, the %ID/g of [131I]-MN-14 IgG in tumour at 10 HALO was 11.50+/-1.58 and at 17 HALO was 1. 5-fold higher at 16.96+/-2.35 (P<0.001). In liver at 10 HALO, uptake was 6.47+/-0.49 and at 17 HALO was 30% lower at 4.48+/-0.81 (P<0.01). These results suggest that small shifts in the chronobiology of BF in tumour and in normal tissue can have a sizeable impact on the distribution of chemotherapeutics and antibody-based drugs.  相似文献   

17.
Changes in human skin blood flow by hyperthermia   总被引:1,自引:0,他引:1  
The heat-induced changes in blood circulation in human forearm skin were studied. With the use of laser Doppler flowmetry, it was possible to noninvasively monitor the velocity and volume of red cells, and thus the flow rate of red cells or blood flow in the human skin. When the skin surface was heated at 35 degrees -43 degrees C for 60 min, the laser Doppler flow (LDF) changed dynamically, indicating that the blood flow in human forearm skin could increase as much as 15-20 times during heating at 43 degrees C. Such an increase in laser Doppler flow resulted from dilation of arterioles and recruitment of capillaries, and also to a lesser extent, from an increase in the velocity of red cell flux. The increase in the velocity of red cell flux implies that arteriovenous anastomoses exist in the human forearm skin, in contradiction to the common view that human forearm skin is devoid of arteriovenous anastomosis.  相似文献   

18.
Angiotensin II (ATII) has potential for improving delivery of blood-borne anti-cancer agents to tumours by increasing tumour blood flow. However, ATII-induced hypertension is not always accompanied by an increase in tumour blood flow due to significant constriction of the tumour vasculature. Such unpredictability in tumour response to ATII limits the clinical usefulness of this approach. In this study, the potential of assessing numbers of binding sites for ATII as a predictor of tumour blood flow response to intravenous administration of ATII was investigated. The distribution of ATII receptors in the rat P22 carcinosarcoma was related to tumour blood flow distribution and blood flow response to ATII using an autoradiographic approach. ATII (0.2 μg · kg−1 · min−1) increased mean arterial blood pressure of anaesthetized BD9 rats from 92.2 ± 1.4 mmHg to 145.6 ± 1.3 mmHg. Despite this increase in perfusion pressure, overall tumour blood flow to viable regions decreased by 20%, indicating significant constriction of tumour blood vessels. Autoradiographic localisation of tumour blood flow showed that the decrease in flow was confined to the tumour periphery, with no change at the tumour centre. This pattern was consistent with 10% more binding sites for ATII at the tumour periphery than at the tumour centre. Maximum number of binding sites (BLmax) for the P22 tumour was 0.38 ± 0.09 fmol · mg−1, which is approximately a factor of 10 lower than published values for various normal tissues. The dissociation constant Kd was 1.16 ± 0.18 nM. These results encourage the development of techniques for analysis of receptor binding characteristics for predicting the response of individual tumours to blood flow manipulation using vasoactive agents. © 1996 Wiley-Liss, Inc.  相似文献   

19.
Oxygen tension measurements were made in three tumors: (i) the murine FSaII fibrosarcoma, (ii) the rat 9L gliosarcoma and (iii) the rat 13672 mammary adenocarcinoma using a pO2 histograph. Tumor oxygenation measurements were made while the animals breathed air or breathed carbogen (95% oxygen/5% carbon dioxide). Pentoxifylline or a perflubron emulsion was administered to the animals and tumor oxygen measurements were repeated under both breathing conditions. Both pentoxifylline and the perflubron emulsion improved the oxygenation of the FSaII fibrosarcoma under air breathing conditions but did not alter the oxygen profiles of either rat tumor compared with air breathing alone. Carbogen breathing increased the oxygenation of all tumors. Pentoxifylline administration did not change the oxygen profiles of the tumors under carbogen breathing conditions but administration of the perflubron emulsion increased the oxygenation of all three tumors under carbogen breathing conditions compared with carbogen breathing alone. Co-administration of pentoxifylline and the perflubron emulsion enhanced the radiation response of the Lewis lung tumor to daily fractionated radiation under air breathing conditions with a dose modifying factor of 1.65 and under carbogen breathing conditions with a dose modifying factor of 2.25. Over a range of perflubron emulsion doses, pentoxifylline increased the growth delay of the Lewis lung tumor in a constant manner. These results indicate that pentoxifylline and the perflubron emulsion have the largest impact on the oxygenation of more hypoxic tumors and that administration of the perflubron emulsion/carbogen breathing is the most effective means of increasing tumor oxygenation and radiation response.  相似文献   

20.
To examine the effect of platelet-active drugs on the spread of blood-borne tumour cells, two murine tumours, sarcoma 180 (S-180) and TLX-5 lymphoma, were selected. Following intravenous (IV) injection into CBA mice the former elicited thrombocytopenia and formed discrete pulmonary tumours, whereas the latter failed to elicit thrombocytopenia and formed discrete tumours in all visceral organs examined except the lungs. S-180 cells were injected IV into mice pre-treated with RA233 (known to prevent thrombocytopenia and thrombus formation) and TLX-5 cells were injected IV into mice pre-treated with Corynebacterium parvum (known to induce thrombocytopenia and thrombus formation). RA233 pre-treatment did not change survival time or incidence of S-180 pulmonary tumours but did result in a higher incidence of extrapulmonary tumours and a lower tumour cell burden immediately after injection. Pre-treatment with C. parvum resulted in a higher TLX-5 tumour cell burden but not discrete tumours in the lungs. On the basis of known drug activities it is proposed that thrombocytopenia induced in these experiments is in part a reflection of thrombus formation in the lungs which influences the speed of passage of tumour cells through capillaries. In some cases this may lead to a changed anatomical distribution of tumour lesions.  相似文献   

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