New alkylamides from the pericarps of Zanthoxylum schinifolium.

The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage.

Structurally diverse alkaloids from the Buxus sinica and their cytotoxicity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sinica resulted in the identification of forty-one Buxus alkaloids, including twenty undescribed ones, namely cyclobuxusinines A-I (1-7, 16 and 20), as well as secobuxusinines A-K (8-15 and 17-19). Their structures were delineated by detailed analysis using various spectroscopic techniques. cyclobuxusinines B (2) was the first Buxus alkaloid, whose CH3-18 was oxidized, implying the presence of special oxidative enzymes in this plant. Secobuxusinines C (10), D (11), and E (12), whose C-12 or C-19 have an OH group substitution, enriched the substituent pattern in Buxus alkaloid and suggested more structurally diverse alkaloids in the Buxus spp. In the assessment of their bioactivities, some of them exhibited significant cytotoxic effects on two human tumor ovarian cancer cell lines. Notably, compound 36 displayed more potent cytotoxic effect against ES2 and A2780 cell lines with the IC50 value of 1.33 µM and 0.48 µM, respectively.

Four undescribed pyrethrins from seeds of Pyrethrum cinerariifolium and their aphidicidal activity.

Four undescribed pyrethrins C-F (1-4) as well as four known pyrethrins (5-8) were isolated from seeds of Pyrethrum cinerariifolium Trev. The structures of compounds 1-4 were elucidated by UV, HRESIMS, and NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC and ROESY), among which the stereostructure of compound 4 was determined by calculated ECD. Furthermore, compounds 1-4 were evaluated for their aphidicidal activities. The insecticidal assay results showed that 1-4 exhibited moderate aphidicidal activities at the concentration of 0.1 mg/mL with the 24 h mortality rates ranging from 10.58 to 52.98%. Among them, pyrethrin D (2) showed the highest aphidicidal activity, with the 24 h mortality rate of 52.98%, which was slightly lower than the positive control (pyrethrin II, 83.52%).

Structural characterizations and α-glucosidase inhibitory activities of four Lepidium meyenii polysaccharides with different molecular weights.

Four polysaccharides (MCPa, MCPb, MCPc, MCPd) were obtained from Lepidium meyenii Walp. Their structures were characterized by chemical and instrumental methods including total sugar, uronic acid and protein content determination, UV, IR and NMR spectroscopy, as well as monosaccharide composition determination and methylation analyses. Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa, and shared a similar backbone chain consisting of (1→4)-glucose linkages with branches attached to C-3 and C-6. Furthermore, bioactivity assay showed that MCPs had concentration-dependent inhibitory activity on α-glucosidase. MCPb (Mw = 10.1 kDa) and MCPc (Mw = 5.62 kDa) with moderate molecular weights exhibited higher inhibitory activity compared with MCPa and MCPd.

NMR-tracking for 15,16-seco-cycloartane triterpenes from Cimicifuga acerina.

Twelve undescribed 15,16-seco-cycloartane triterpenoids, 15,16-seco-cimiterpenes C-N, as well as five previously reported analogs were isolated by NMR-tracking methods from the rhizomes of Cimicifuga acerina (Sieb. et Zucc.) Tanaka. Among them, 15,16-seco-cimiterpenes C-N were the first 15,16-seco-cycloartane triterpenoids featuring acetal or hemiacetal structures at C-15. The chemical structures of 15,16-seco-cimiterpenes C-N were determined based on comprehensive spectroscopic analysis, chemical method, and comparison with the previous literature data. After that, all these compounds were evaluated for their lipid-lowering effects on 3T3-L1 adipocytes.15,16-seco-cimiterpene D was found to exhibit a comparable reducing lipid effect at the concentration of 50 µM, with an inhibition rate at 35.96%.

The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.

INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast. MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3). RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic. CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.

Application of ultrasonography in predicting the biological risk of gastrointestinal stromal tumors.

OBJECTIVES: To explore and establish a reliable and noninvasive ultrasound model for predicting the biological risk of gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: We retrospectively reviewed 266 patients with pathologically-confirmed GISTs and 191 patients were included. Data on patient sex, age, tumor location, biological risk classification, internal echo, echo homogeneity, boundary, shape, blood flow signals, presence of necrotic cystic degeneration, long diameter, and short/long (S/L) diameter ratio were collected. All patients were divided into low-, moderate-, and high-risk groups according to the modified NIH classification criteria. All indicators were analyzed by univariate analysis. The indicators with inter-group differences were used to establish regression and decision tree models to predict the biological risk of GISTs. RESULTS: There were statistically significant differences in long diameter, S/L ratio, internal echo level, echo homogeneity, boundary, shape, necrotic cystic degeneration, and blood flow signals among the low-, moderate-, and high-risk groups (all p < .05). The logistic regression model based on the echo homogeneity, shape, necrotic cystic degeneration and blood flow signals had an accuracy rate of 76.96% for predicting the biological risk, which was higher than the 72.77% of the decision tree model (based on the long diameter, the location of tumor origin, echo homogeneity, shape, and internal echo) (p = .008). In the low-risk and high-risk groups, the predicting accuracy rates of the regression model reached 87.34 and 81.82%, respectively. CONCLUSIONS: Transabdominal ultrasound is highly valuable in predicting the biological risk of GISTs. The logistic regression model has greater predictive value than the decision tree model.

Can Nonfibrotic Nonalcoholic Steatohepatitis Be Effectively Identified by Supersonic Shear Imaging?

Supersonic shear imaging (SSI) is a relatively new technique to measure the elasticity of target tissues based on the shear wave propagation. The aim of this study was to evaluate the value of SSI in discriminating nonfibrotic nonalcoholic steatohepatitis (NASH) from the less severe nonalcoholic fatty liver disease (NAFLD), NASH with fibrosis, and the normal liver, as well as the relationship between various NAFLD pathologic or biochemical findings and SSI liver elasticity. Rabbits with NAFLD of different degrees were subjected to SSI for liver elasticity measurement. Plasma was collected for biochemical examinations, and liver tissues were harvested for pathologic assessment. Results showed that liver elasticity of rabbits with nonfibrotic NASH was significantly different from that of rabbits with simple steatosis, borderline, NASH with fibrosis, and normal liver (P < 0.05) and the areas under the receiver operating characteristic curve of SSI for predicting nonfibrotic NASH and NASH with fibrosis were 0.997 and 0.967, respectively, and the optimal cutoff values were 10.17 kPa and 12.82 kPa, respectively. Multivariate analysis showed that only fibrosis and inflammation were the independent factors affecting liver elasticity of NAFLD (P ≤ 0.001), while inflammation, steatosis, and ballooning degeneration were all independently related to liver elasticity in rabbits without fibrosis (P < 0.01). In addition, alanine aminotransferase was the only biochemical factor independently related to liver elasticity (P ≤ 0.001). Our results indicate that SSI can effectively identify nonfibrotic NASH in rabbits based on the difference in liver elasticity and the difference is related to the various pathologic changes, including fibrosis, inflammation, steatosis, and ballooning degeneration.

[Microbubbles targeted to P-selectin for evaluating testicular ischemia-reperfusion injury in rabbits].

OBJECTIVE: To explore the feasibility of evaluating complete ischemia-reperfusion injury (IRI) of the testis by contrast-enhanced ultrasonography with microbubbles (MB) targeted to P-selectin (MBp) in rabbits. METHODS: We randomly divided 30 healthy adult rabbits into five groups of equal number (control, 0.5 h IRI, 1 h IRI, 2 h IRI, and 4 h IRI), prepared phospholipid MB and MBp, and performed contrast-enhanced ultrasonography of the bilateral testes with MB or MBp at an interval of 20 min at different times after IRI. When MB or MBp disappeared completely in the healthy testis at 4 to 5 min after intravenous injection, we recorded the power of the first frame (F-P) in the IRI testes followed by immunohistochemical staining of the testis tissue. RESULTS: CEU with MBp achieved a significantly higher F-P than that with MB in all the IRI groups (P < 0.05), which was (8.34 +/- 1.20) versus (1.87 +/- 0.25) 10(-5) AU at 2 hours, but there was no significant difference between MB and MBp in the control rabbits (0 AU, P > 0.05). Immunohistochemistry showed a significantly time-dependent increase in the expression of P-selectin in the vascular endothelial cells of the IRI testes, but not in those of the control. CONCLUSION: Contrast-enhanced ultrasonography with MBp can be used to evaluate the inflammatory reaction of testicular ischemia-reperfusion injury.

Ultrasound exposure improves the targeted therapy effects of galactosylated docetaxel nanoparticles on hepatocellular carcinoma xenografts.

PURPOSE: The distribution of targeted nanoparticles in tumor tissue is affected by a combination of various factors such as the physicochemical properties of the nanoparticles, tumor hemoperfusion and tumor vascular permeability. In this study, the impact of the biological effects of ultrasound on nanoparticle targeting to liver carcinoma was explored. METHODS: The copolymer MePEG-PLGA was used to prepare the galactosylated docetaxel nanoparticles (GDN), and the physical and chemical properties as well as the acute toxicity were then assayed. The impact of ultrasound exposure (UE) on tumor hemoperfusion was observed by contrast-enhanced ultrasonography (CEUS), and the distribution of docetaxel in tumors and liver were detected by high performance liquid chromatography (HPLC). In the GDN combined with UE treatment group, the mice were injected intravenously with GDN, followed by ultrasound exposure on the human hepatocellular carcinoma xenografts. Twenty-eight days post-administration, the tumor growth inhibition rate was calculated, and the expression of Survivin and Ki67 in tumor tissues were determined by immunohistochemistry assay and quantitative real-time PCR. RESULTS: The mean size of prepared liver-targeting nanoparticles GDN was 209.3 nm, and the encapsulation efficiency was 72.28%. The median lethal dose of GDN was detected as 219.5 mg/kg which was about four times higher than that of docetaxel. After ultrasound exposure, the tumor peak - base intensity difference value, examined by CEUS, increased significantly. The drug content in the tumor was 1.96 times higher than in the GDN treated control. In vivo, GDN intravenous injection combined with ultrasound exposure therapy achieved the best anti-tumor effect with a tumor growth inhibition rate of 74.2%, and the expression of Survivin and Ki67 were significantly decreased as well. CONCLUSION: Ultrasound exposure can improve targeting nanoparticles accumulation in the tumor, and achieve a synergism antitumor effect on the hepatocellular carcinoma xenografts.

Effect of interstitial chemotherapy with ricin temperature-responsive gel for anti-breast cancer and immune regulation in rats.

OBJECTIVE: To explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats. METHODS: Ricin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups. RESULTS: The TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01). CONCLUSION: Intratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and cobra venom cytotoxin.

Cobra venom cytotoxin (CVC) loaded in poly (lactide-co-glycolide) (PLGA) microspheres was mixed with ricin and encapsulated in a thermosensitive PLGA-PEG-PLGA hydrogel for this study. This sequential sustained-release preparation (SSRP) containing ricin and CVC could avoid burst release effect of CVC from microspheres. In addition, in SSRP, the two biotoxins have different drug release rates and antitumor mechanisms, which can be complementary to each other. Ricin has a faster release rate than CVC. It can combine with the tumor cell membrane and enter the cell, inhibiting protein synthesis within 2 weeks. Whereas CVC releases slowly in 5 weeks directly dissolving the tumor cell membrane and killing the cells which are less-sensitive to ricin. The in vivo experiments showed that intratumoral injection of SSRP could inhibit hepatocellular carcinoma growth significantly, and the tumor growth inhibition rate reached 73.5%. It appears that a new medicine preparation for cancer local treatment should be further studied for clinical applications.

Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft.

To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity.

[Impact of unilateral acute testicular ischemia on the contralateral testis of rabbits in anesthetic and conscious states].

OBJECTIVE: To compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state. METHODS: Forty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non-anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states. RESULTS: PS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2. CONCLUSION: Acute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis.

[Ischemic postconditioning reduces testis ischemia-reperfusion injury in rabbits].

OBJECTIVE: To investigate the protective effect of ischemic postconditioning (IP) against different degrees of testicular ischemia-reperfusion (IR) injury in rabbits. METHODS: Forty-two white male rabbits were equally randomized into 7 groups: a control, 3 IR (R1, R2 and R3), and 3 IP (P1, P2 and P3) groups. Testicular models of different degrees of ischemia were established in the IR and IP groups. Before reperfusion, ultrasonography showed homogeneous echoes with slightly decreased blood flow in R1 and P1, heterogeneous echoes with obviously decreased blood flow in R2 and P2, lamellar or fragmental low echo areas absent of blood flow signals in R3 and P3. Then the IR groups were directly subjected to perfusion, and the IP groups to 3 episodes of 30-second reperfusion followed by 30-second ischemia. All the groups underwent contrast-enhanced ultrasonography (CEUS) before reperfusion and, after 3 days, examined for the contents of malonaldehyde (MDA), superoxide dismutase (SOD) and histology, and observed for the pathological changes of the testicular tissue. RESULTS: Before reperfusion, no significant differences were found in the CEUS parameters beta, time-to- peak (TTP), peak-base intensity (PBD) and half of declining time (DT/2) between R1 and P1, R2 and P2, and R3 and P3 (P>0.05). There were remarkable differences in MDA and SOD between R1 and P1, and R2 and P2 (P<0.05), but not between R3 and P3 (P >0.05). Johnson's score, apoptosis index and ultrastructure showed marked differences between R1 and P1 (P<0.05) but not between R2 and P2, and R3 and P3 (P >0.05). CONCLUSION: IP can attenuate IR-induced testis injury, but the effect varies with the degree of ischemia, and its pathological manifestation differs from the biochemical one.

Mixed template effect adjusted by amine concentration in ionothermal synthesis of molecular sieves.

Cationic templating of imidazolium adjusted by the amine concentration in an ionothermal system results in products with larger channels or cage-like structures by reassembling the inorganic hosts around the changed organic guests.

[Ultrasonographic appearance of experimental testicular ischemia and protective effect of allopurinol].

OBJECTIVE: To investigate the correlation of the ultrasonographic appearance of different degrees of experimentally induced acute unilateral testicular ischemia with the protective effect of allopurinol. METHODS: Forty-two male white rabbits were equally randomized into 7 groups: sham-operation control, ischemic A, B and C, and treatment D, E and F. Models of different degrees of unilateral testicular ischemia were established in the ischemic and treatment groups under the dynamic observation by color Doppler ultrasound. The ischemic testes showed slightly decreased homogeneous echoes and flow signals in groups A and D, obviously decreased heterogeneous echoes and flow signals in groups B and E, and radial or fragmental low-echo areas and disappearance of flow signals in groups C and F. The ischemic groups received reperfusion after the appearance of the above ultrasonographic changes, while the treatment groups following the intraperitoneal injection of allopurinol at 200 mg/kg. Contrast-enhanced ultrasonography (CEUS) was performed on the bilateral testes before and 3 days after the reperfusion. After 3 days of breeding, the histological changes and malondialdehyde (MDA) contents of the ischemic testes were observed, and the correlation was analyzed between the protective effect of allopurinol and the ultrasonographic appearance of different degrees of acute unilateral testicular ischemia. RESULTS: CEUS showed fast wash-in and fast wash-out in the sham-operation control group, slow wash-in and slow wash-out in groups A and B and extensive central filling defect in group C before the reperfusion. Fast wash-in and slow wash-out were observed in all the ischemic groups 3 days after the reperfusion, most obviously in group C. Groups D, E and F exhibited the same CEUS appearance as A, B and C before and 3 days after the reperfusion. Johnsen's scores were significantly increased in groups D (9.10 +/- 0.23) and E (7.03 +/- 0.20) in comparison with A (8.53 +/- 0.22) and B (5.82 +/- 0.33) (P < 0.05), but with no significant differences between C (2.30 +/- 0.53) and F (2.45 +/- 0.33) (P > 0.05). The rates of apoptosis were significantly decreased in groups D ([1.68 +/- 0.43]%) and E ([12.53 +/- 0.59]%) compared with A ([7.12 +/- 0.84]%) and B ([20.87 +/- 1.59]%) (P < 0.05), but with no significant differences between C ([52.93 +/- 2.62 ]%) and F ([51.23 +/- 2.53 ]%) (P > 0.05). Significant decreases of MDA contents in the ischemic testes were observed in groups D ([0.64 +/- 0.05] nmol/mg prot), E ([1.59 +/- 0.06] nmol/mg prot) and F ([3.10 +/- 0.17] nmol/mg prot) in comparison with A ([1.38 +/- 0.07] nmol/mg prot), B ([2.11 +/- 0.08] nmol/mg prot) and C ([3.25 +/- 0.14] nmol/mg prot) (P < 0.05). CONCLUSION: Allopurinol contributes to the recovery of spermatogenesis when testicular ischemia is sonographically shown to be mild or moderate, but produces no significant effect when it is shown to be severe. Ultrasonography helps to choose the right therapy of testicular torsion and predict spermatogenesis of ischemic testes after reperfusion.

Interstitial chemotherapy using thermosensitive gel-coated ricin in nude mice bearing a human hepatoma.

AIM: To investigate the anti-tumor effects and mechanisms of interstitial chemotherapy using intra-tumor injection of thermosensitive gel-coated ricin in nude mice bearing a human hepatoma. METHODS: In a subcutaneous mouse model of hepatoma, saline, blank gel, ricin, or thermosensitive gel-coated ricin (TGR) was injected directly into tumors. Fourteen days later, eight mice in each group were sacrificed. The tumors were removed and weighed for calculating tumor growth inhibition rate. Serum alpha-fetoprotein levels, as well as hepatic and renal functions, were measured. Tumor tissue was analyzed under an optical microscope. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling was used to detect the apoptotic index. Moreover, caspase-3 activity and protein expression in tumor tissue were examined. The survival time of the tumor bearing mice was determined. RESULTS: Following interstitial chemotherapy by intra-tumor injection of TGR in nude mice, serum alpha-fetoprotein levels were significantly reduced with no significant impact on hepatic or renal functions. The rate of tumor growth inhibition was 58.5% following a single, local injection. Histological analysis revealed abundant necrosis. The apoptotic index was 45.96 +/- 7.41%. Caspase-3 activity was increased, and caspase-3 protein was significantly activated in tumor cells. Compared to the saline group, the survival time of mice in the TGR group was significantly extended. At the observation terminal time, day 120, two mice were still alive and fully recovered. CONCLUSION: Interstitial chemotherapy by intra-tumor injection of TGR was highly efficient and safe for the treatment of nude mice bearing a human hepatoma. Interstitial chemotherapy exhibits inhibitory effects by inducing apoptosis and directly killing tumor cells.