| BACKGROUNDHigh intensity focused ultrasound(HIFU)is a new non-invasive etchnique to treat solid tumors,but it can't be always success when treating deep tumors and big tumors in experiment and in clinic. We have many ways to chose to reslove these problems, but they all have problemw in safety and non-invasive. So the bettle way is to change the acoustic enviorment of the tissue. The acoustiocal characteristic of tissue include velocity of sound, acoustic impedance, reduction coefficient, backscattering coefficient and acoustic nonlinearity parameter. When the structure and the function ot the tissue were changed, we could change the acoustic enviorment in the tissues if one of the acoustiocal characteristic of tissue was abnormal. So many investigators at home and abroad all want to find a kind of synergist used in vitro to change the acoustiocal characteristic of tissue, then to boost up the curative effect of HIFU theraphy.It have a lot of means and drugs in study to enhance the curative effect of HIFU theraphy at present, but there is no one can be used safely and efficiently in clinic. In recent years, the investigators found that the nano-hydroxyapatite(nano-HA) could restrain the proliferation of many kinds of tumor cells in vitro, while had lightly infection to normal tissue cells. In our previous studies we found that nan-HA could be intravenous injected and accumulated in the liver tissues, then to make the srtuctuer and ruction changed in some time. However, it is still unclear whether these changes could cause the acoustiocal characteristic of tissue and the acoustic enviorment of the tissue different, and to enhance the HIFU theraphy. Onthe other hand it is also unclear whether nano-HA could kill tumor cells when intravenous injected.OBJECTIVEThe objectives of thes study are described as follows:1 To investigate the particle size and shape of nano-HA, and to evaluate the safity of nano-HA to rabbits with intravenous application.2 To study the effects of nano-HA on the focus ultrasound theraphy when rabbits livers were directively tangent treated in vivo, and the machanism of nano-HA in enhancing the curative effects of HIFU were evaluated.3 To investigate the effects of nano-HA on the HIFU theraphy to rabbits' liver and goats" liver in vitro.4 To establish the model of inplanted VX2 liver cancer model on rabbits liver, and to investigate the effects of nano-HA on the focus ultrasound theraphy to the rabbits' inplanted liver cancer.METHODS1 The particle size and the shape of nano-HA were observed by transmission electron microscope, SPSS 10.0 statistical software was performed for the statistical analysis.2 A total of 60 New Zealand rabbits were randomized of two groups as follows: group A, for the study to lethal dose of nano-HA; group B, for the study of effects of nano-HA on the function of rabbits' liver and renal, and enzyme,etc. The survial rate and survial time of the rabbits in group A were observed. Biological characteristics, morphologic ,histological changes and functions of important apparatuses were observed in grup B. SPSS 10.0 statistical software was performed for the statistical analysis.3 A total of 120 New Zealand rabbits were randomized to three groups, for the study of the effects of three factors of nano-HA on the focus ultrasound theraphy. The three factors were the dosage of nano-HA, the time to focus ultrasound theraphy after nano-HA injection and the different solvents. Biological characteristics, morphologic ,histological changes were observed by light miceoscope and transmission electron microscope. The tempreature and the volume of the coagulative necrosis were checked, the energy efficiency factor( EEF) was analyized. SPSS 10.0 statistical software was performed for the statistical analysis.4 A total of 40 New Zealand rabbits were randomized to two groups asfollows: control gropp(with 0.9% saline injected by vein); nano-HA group(with nano-HA 50mg/kg intravenous injected). The two groups received HIFU exposure in vivo after drugs injection for 24 hours ,respectively. The course of treatment was supervised by real-time ultrasound, and the relationship between the ultrasound image and the factual coagulative necrosis was analysed. Biological characteristics, morphologic ,histological changes were observed by light miceoscope and transmission electron microscope. The volume of the coagulative necrosis were checked, the energy efficiency factor(EEF) was calculated. SPSS 10.0 statistical software was performed for the statistical analysis.5 A total of 30 south Sinkiang gazzxle were randomized to two groups as follows: control group and nano-HA group, received HIFU dot exposure and live exposure in vitro. The volume of the coagulative necrosis were checked, the energy efficiency factor(EEF) was calculated. SPSS 10.0 statistical software was performed for the statistical analysis.6 A total of 60 New Zealand white rabbits were used to establish transplanted VX2 liver cancer model. They were randomized to twogroups: one group was used to study the effection of focus ultrasound theraphy to rabbits" VX2 liver cancer in vivo with nano-HA application. The other group was used for the study of the effection of HIFU theraphy to the rabbits" VX2 liver cancer in vitro with nano-HA application. The course of treatment, the growth and proliferation of tumors were follow-up surveyed by real-time ultrasound. Histological changes were examined , and the survial rate and survial time of rabbits were observed.RESULTS1 Nnao-HA was a kind of needleshaped microcrystle observed by transmission electron microscope, the mean particle size was 15.26±2.39nm * 82.82±42.25nm, more less than the diameter of human capillary vessel.2 The LD50 of nano-HA to rabbits was 200 mg/kg. The influence of nano-HA applied by vein to the live friction and the kidney faction of rabbits were all exhibited from 2 hours to 72 hours after injection, and severe side-effect and sequelae were not found.3 The enhancing effection of nano-HA to focus ultrasound theraphy in vivo was 1.99-3.02 times compared with control group. The feasible dosage of nano-HA was 50mg/kg, the better exposue time to receive ultrsound theraphy was from 24 hours to 72 hours after nan-HA application, and the plain and utilitarian dipersant was 0.9%saline.4 The enhancing effection of nano-HA to HIFU treating rabbits" liver in vitro was 2.88-3.4 times compared with control group, and about 3.5 times to HIFU treating goats" liver.5 The transplanted rabbit's VX2 liver cancer could be ablated completely by focus ultrasound or HIFU with nano-HA application in vivo and in vitro. The two ways could prolong the survial times of the animals.
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