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1.
Fitoterapia ; 177: 106057, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38844141

RESUMEN

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.


Asunto(s)
Zanthoxylum , Zanthoxylum/química , Animales , Estructura Molecular , Ratas , Células PC12 , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Amidas/química , Amidas/aislamiento & purificación , Amidas/farmacología , Corticosterona
2.
Nat Prod Bioprospect ; 13(1): 22, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37415012

RESUMEN

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%).

3.
Nat Prod Bioprospect ; 13(1): 18, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37278859

RESUMEN

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.

4.
Scand J Gastroenterol ; 57(3): 352-358, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34779685

RESUMEN

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.


Asunto(s)
Tumores del Estroma Gastrointestinal , Endosonografía , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/patología , Humanos , Modelos Logísticos , Estudios Retrospectivos , Ultrasonografía
5.
Zhonghua Nan Ke Xue ; 20(6): 500-4, 2014 Jun.
Artículo en Chino | MEDLINE | ID: mdl-25029853

RESUMEN

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.


Asunto(s)
Anticuerpos , Selectina-P/inmunología , Daño por Reperfusión/diagnóstico por imagen , Testículo/irrigación sanguínea , Animales , Modelos Animales de Enfermedad , Masculino , Microburbujas , Conejos , Ultrasonografía
6.
Chin J Integr Med ; 19(1): 48-53, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21717157

RESUMEN

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.


Asunto(s)
Antineoplásicos/administración & dosificación , Inmunomodulación/efectos de los fármacos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Ricina/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Relación CD4-CD8 , Modelos Animales de Enfermedad , Femenino , Geles/uso terapéutico , Inmunohistoquímica , Inyecciones Intralesiones , Interleucina-2/inmunología , Interleucina-2/metabolismo , Neoplasias Mamarias Experimentales/inmunología , Neoplasias Mamarias Experimentales/patología , Distribución Aleatoria , Ratas , Ratas Wistar , Sensibilidad y Especificidad , Temperatura , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
7.
Pharmazie ; 67(7): 618-21, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22888519

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Venenos Elapídicos/administración & dosificación , Venenos Elapídicos/farmacología , Ricina/administración & dosificación , Ricina/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada , Portadores de Fármacos , Venenos Elapídicos/química , Excipientes , Humanos , Hidrogeles , Ácido Láctico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica de Rastreo , Microesferas , Trasplante de Neoplasias , Tamaño de la Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ricina/química , Temperatura , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Med Oncol ; 29(1): 62-9, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21136211

RESUMEN

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.


Asunto(s)
Antineoplásicos/administración & dosificación , Ácido Láctico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Microesferas , Neovascularización Patológica/tratamiento farmacológico , Ácido Poliglicólico , Taxoides/administración & dosificación , Angiopoyetina 2/biosíntesis , Animales , Preparaciones de Acción Retardada/farmacología , Docetaxel , Portadores de Fármacos , Femenino , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Neovascularización Patológica/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Zhonghua Nan Ke Xue ; 17(10): 873-9, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22049787

RESUMEN

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.


Asunto(s)
Isquemia/patología , Daño por Reperfusión/patología , Enfermedades Testiculares/patología , Testículo/patología , Animales , Modelos Animales de Enfermedad , Isquemia/diagnóstico por imagen , Masculino , Conejos , Daño por Reperfusión/diagnóstico por imagen , Enfermedades Testiculares/diagnóstico por imagen , Testículo/irrigación sanguínea , Testículo/diagnóstico por imagen , Ultrasonografía
10.
Zhonghua Nan Ke Xue ; 17(2): 115-20, 2011 Feb.
Artículo en Chino | MEDLINE | ID: mdl-21404706

RESUMEN

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.


Asunto(s)
Poscondicionamiento Isquémico , Daño por Reperfusión , Testículo/patología , Animales , Masculino , Malondialdehído/análisis , Conejos , Superóxido Dismutasa/análisis
11.
Zhonghua Nan Ke Xue ; 16(12): 1083-8, 2010 Dec.
Artículo en Chino | MEDLINE | ID: mdl-21348198

RESUMEN

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.


Asunto(s)
Alopurinol/farmacología , Daño por Reperfusión/diagnóstico por imagen , Enfermedades Testiculares/diagnóstico por imagen , Testículo/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Isquemia/diagnóstico por imagen , Masculino , Conejos , Ultrasonografía
12.
J Cancer Res Clin Oncol ; 136(4): 537-45, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19777257

RESUMEN

INTRODUCTION: This study aims to investigate the therapeutic effect of paclitaxel temperature-responsive gel (PTRG) for interstitial chemotherapy on breast cancer, and to explore a new minimally invasive treatment for breast cancer. MATERIALS AND METHODS: Breast cancer models were induced in rats using subcutaneous transplantation of tumor cells. The rats were then divided into control, paclitaxel injection, gel injection and paclitaxel-gel (PG) group. Following treatment, all animals were checked regularly by ultrasonography to observe changes in the tumors. Biopsy tumor tissues were processed for histopathological examination, and apoptotic index was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling method. In addition, blood cell count and liver transaminase activity were monitored, and the survival time of rats with cancer recorded. RESULTS: Rats in PG group exhibited liquefaction necrosis of tumors. Ninety days after the experiment, four rats exhibited complete extinction of tumors, indicating full recovery. Pathological examination revealed that the tumor tissues in these rats were mostly necrotic, and the apoptotic index of tumor cells increased markedly compared to PI group. Also, the red blood cell, hemoglobin and white blood cell levels declined significantly in the PI group compared with PG group, while glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase activities significantly increased. Meanwhile, no toxicity due to treatment was observed in PG group. CONCLUSION: Interstitial chemotherapy mediated by PTRG appeared to be a safe and effective treatment for breast cancer in rats. It might have clinical applications for treating human breast cancer.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Paclitaxel/administración & dosificación , Polietilenglicoles/química , Poliglactina 910/química , Temperatura , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis , Biomarcadores de Tumor/metabolismo , Vías de Administración de Medicamentos , Femenino , Geles , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Neoplasias Mamarias Experimentales/patología , Paclitaxel/uso terapéutico , Ratas , Ultrasonografía
13.
Hepatol Res ; 40(2): 188-95, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19788688

RESUMEN

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.

14.
Zhong Xi Yi Jie He Xue Bao ; 7(9): 836-41, 2009 Sep.
Artículo en Chino | MEDLINE | ID: mdl-19747438

RESUMEN

OBJECTIVE: To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. METHODS: Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. RESULTS: The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)microm. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. CONCLUSION: The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Venenos Elapídicos/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Microesferas , Animales , Humanos , Inyecciones Intralesiones , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Distribución Aleatoria
15.
Hepatobiliary Pancreat Dis Int ; 8(4): 418-23, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19666413

RESUMEN

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, and has a poor prognosis. Despite efforts made in multiple fields, there has been little success in improving the disease-free survival rate of patients. This study was undertaken to investigate the effectiveness and feasibility of using intra-tumoral injection of ricin-loaded thermosensitive hydrogel for treatment of pancreatic cancer xenografts, attempting to develop a new treatment for human pancreatic cancer. METHODS: BALB/c-(nu/nu) nude mice were inoculated subcutaneously in the right flank with the human pancreatic cancer cells, SW1990. Fourteen days after inoculation, 32 mice, bearing tumors of volume 1.5-2.0 cm3, were randomly assigned to one of four groups, and given an intra-tumoral injection of: (1) saline; (2) 23% w/w thermosensitive hydrogel alone; (3) ricin, 10 microg/kg; or (4) 10 microg/kg ricin loaded in thermosensitive hydrogel. On day 14 after administration, the tumors were excised to calculate the inhibition rate of tumor growth and perform histopathological examination. Tumor cell apoptosis was detected by flow cytometry, and RT-PCR was performed to evaluate the mRNA expression levels of Bcl2 and Bax. RESULTS: Intra-tumoral injection of ricin-loaded thermosensitive hydrogel resulted in remarkable control of tumor growth. The tumor became necrotic by day 14 after administration. The histological results clearly confirmed that the tumor cells were lysed. The percentage of apoptotic cells detected by flow cytometry was higher in the ricin hydrogel group than in the other groups. Semi-quantitative RT-PCR revealed that the mRNA expression level of Bcl2 was down-regulated whereas Bax was upregulated. CONCLUSIONS: Intra-tumoral injection of ricin-loaded thermosensitive hydrogel may provide an effective approach for interstitial chemotherapy in pancreatic cancer. Inducing apoptosis by downregulating Bcl2 expression and upregulating Bax expression may be a key molecular mechanism.


Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos , Hidrogeles , Neoplasias Pancreáticas/tratamiento farmacológico , Polietilenglicoles/química , Poliglactina 910/química , Ricina/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Inyecciones Intralesiones , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Necrosis , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Temperatura , Factores de Tiempo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética
16.
Zhong Xi Yi Jie He Xue Bao ; 7(5): 447-52, 2009 May.
Artículo en Chino | MEDLINE | ID: mdl-19435559

RESUMEN

OBJECTIVE: To explore the efficacy and feasibility of interstitial chemotherapy using thermosensitive gel-coated ricin in hepatoma H22-bearing mice. METHODS: Ricin was purified by chromatography method. The purified ricin was identified by Western blot assay and the purity was determined by high-performance liquid chromatography. BALB/c mice were inoculated subcutaneously in right flank with hepatoma H22 cells. When the tumor size reached about 1.0 cm in diameter, 40 mice were randomly divided into untreated group, thermosensitive gel group, ricin group and thermosensitive gel-coated ricin group. Mice in each group were administered different agents by percutaneous intratumoral injection, including normal saline, thermosensitive hydrogel, ricin and thermosensitive gel-coated ricin. Fifteen days after treatment, the tumors were removed to calculate inhibition rate of tumor growth. The tumor tissues were made into pathological sections to perform histopathological examination. The ultrastructure of tumor tissue was examined by electron microscope examination as well. Blood was collected to detect the hepatic and renal functions. The caspase-3 activity of tumor tissue was determined by using zymologic method with a spectrophotometer. RESULTS: After intratumoral therapy, tumor weight in the thermosensitive gel-coated ricin group was lower than that in the untreated group, with a tumor growth inhibition rate of 71.31%. No obvious hepatic or renal toxicities were detected after thermosensitive gel-coated ricin treatment. Histopathologic observation of the tumor tissue showed massive necrosis and typical apoptosis phenomena, including chromatin margination and apoptotic body. Meanwhile, thermosensitive gel-coated ricin resulted in a significant increase in the caspase-3 activity as compared with the untreated group and the ricin group (P<0.01, P<0.05). CONCLUSION: The above findings indicate that intratumoral therapy with thermosensitive gel-coated ricin has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Hidrogeles , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Polietilenglicoles/química , Poliglactina 910/química , Ricina/administración & dosificación , Animales , Caspasa 3/metabolismo , Portadores de Fármacos , Inyecciones Intralesiones , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Endogámicos BALB C
17.
Zhonghua Nan Ke Xue ; 15(2): 115-21, 2009 Feb.
Artículo en Chino | MEDLINE | ID: mdl-19323369

RESUMEN

OBJECTIVE: To discuss the correlation between sonographic appearance of different degrees of acute unilateral testicular ischemia and histological changes of the testis after reperfusion. METHODS: Thirty-two male rabbits were equally divided into a control (sham operation) group and 3 ischemia groups. Unilateral testicular ischemia models were established under the color Doppler ultrasound (CDU) observation and allocated according to different degrees of ischemia to Group A (with homogeneous echoes and slightly decreased flow signals), B (with heterogeneous echoes and obviously decreased flow signals) and C (with radial or small-shredded low echoes and absence of flow signals). Then contrast-enhanced ultrasonography (CEUS) was performed, followed by reperfusion of the ischemic testes. A month later, the histological changes of the testes were observed and the correlation of the histological changes with the sonographic and CEUS manifestations was analyzed. RESULTS: Concerning the CEUS parameters such as the arrival time (AT), reperfusion rate, time-to-peak (TTP), half descent time (DT/2) of the ischemic testes, Groups A and B showed significant differences from the control group (P < 0.05). The peak-base difference (PBD) was significant in Group B (P < 0.05) but not in A (P > 0.05), and no enhancement was seen in Group C. As for Johnson's scores obtained 1 month later, Group A exhibited no significant difference (8.70 +/- 0.39) (P > 0.05), Group B showed significant difference (6.01 +/- 0.88) (P < 0.05), and Group C extremely significant difference (3.16 +/- 1.05) (P< 0.001) from the control group (9.10 +/- 0.11). CONCLUSION: CEUS is superior to CDU in evaluating the perfusion of testicular ischemia. Sonographic appearances of testicular ischemia are significantly correlated with histological changes of the testis after reperfusion. Ultrasonography helps to predict the spermatogenetic function of ischemic testes after reperfusion.


Asunto(s)
Daño por Reperfusión/diagnóstico por imagen , Daño por Reperfusión/patología , Enfermedades Testiculares/diagnóstico por imagen , Enfermedades Testiculares/patología , Animales , Modelos Animales de Enfermedad , Isquemia/diagnóstico por imagen , Isquemia/patología , Precondicionamiento Isquémico , Masculino , Conejos , Testículo/diagnóstico por imagen , Testículo/patología , Ultrasonografía Doppler en Color
19.
Zhonghua Nan Ke Xue ; 14(4): 347-50, 2008 Apr.
Artículo en Chino | MEDLINE | ID: mdl-18481430

RESUMEN

OBJECTIVE: To discuss the correlation of ultrasonographic grading of varicocele (VC) with the changes of seminal parameters after varicocelectomy. METHODS: A total of 129 cases of VC were diagnosed by scrotal color Doppler ultrasonography (CDU) and graded into 3 groups: VC I, VC II and VC III, according to three different grading indexes: the regurgitant volume of pampiniform plexus veins (PPV), the maximum diameter of PPV and the combination of the regurgitant volume and the maximum diameter of PPV. All the patients underwent high ligation of the spermatic vein and semen analysis was performed before and after varicocelectomy according to the WHO guidelines. RESULTS: With the maximum diameter of PPV as the grading index, there were statistically significant differences in the seminal parameters of VC III (P < 0.05) but not in those of VC I and VC II (P > 0.05) before and after varicocelectomy, while based on the regurgitant volume of PPV or the combination of the regurgitant volume and the maximum diameter of PPV, the differences were insignificant in VC I (P > 0.05), significant in VC II (P < 0.05) and extremely significant in VC III (P < 0.01). No significant differences were found in the rate of sperm abnormality among the 3 groups after varicocelectomy (P > 0.05). CONCLUSION: Different grading indexes influence the changes of seminal parameters after varicocelectomy. The regurgitant volume of PPV and the combination of the regurgitant volume and the maximum diameter of PPV are more reasonable and reliable as the grading indexes of VC. Different grades of VC respond differently to varicocelectomy. Whether VC I necessitates varicocelectomy needs to be further investigated.


Asunto(s)
Semen/fisiología , Ultrasonografía Doppler en Color/métodos , Varicocele/diagnóstico por imagen , Varicocele/fisiopatología , Adulto , Humanos , Masculino , Semen/citología , Recuento de Espermatozoides , Motilidad Espermática , Varicocele/cirugía
20.
Hepatobiliary Pancreat Dis Int ; 7(2): 169-73, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18397853

RESUMEN

BACKGROUND: Hepatic fungal infection is difficult to diagnose early because of the lack of related clinical knowledge. In this study, we analyzed the ultrasonic manifestations of hepatic fungal infection, in order to determine the diagnostic value of ultrasonography. METHODS: In 8 patients with hepatic fungal infection, the results of color Doppler flow images (CDFI) and contrast-enhanced ultrasonography (CEUS) were compared with those of ultrasound-guided biopsy. RESULTS: In the 8 patients with pathologically proven hepatic fungal infection, 5 showed multiple hypoechoic lesions with unequal sizes in the liver, commonly less than 2 cm in diameter. Some of the hypoechoic lesions showed a hyperechoic strip in the periphery, while a minority showed a "bull's eye" pattern, which is considered a typical manifestation of metastatic hepatic carcinoma. Solitary lesions in the right lobe of the liver were found in the other 3 patients. No blood flow signals were found in any lesions with CDFI. In the lesions a "filling defect" pattern was shown by CEUS, indicating no enhancement in the arterial phase, the portal vein phase and the delayed phase, except for 3 patients, in whom the lesions were slightly enhanced in the periphery during the early arterial phase. CONCLUSIONS: Hepatic fungal infection is characterized by an ultrasonic manifestation of multiple hypoechoic lesions with inequal size. A small number of lesions may show a characteristic "bull's eye" appearance. Moreover, a "filling defect" pattern on CEUS is helpful to make a correct diagnosis. In addition, ultrasound-guided biopsy is an important method for accurate diagnosis of hepatic fungal infection.


Asunto(s)
Hepatitis/diagnóstico por imagen , Micosis/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Adulto , Biopsia , Velocidad del Flujo Sanguíneo , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Hepatitis/microbiología , Hepatitis/fisiopatología , Humanos , Hígado/diagnóstico por imagen , Hígado/microbiología , Hígado/patología , Masculino , Persona de Mediana Edad , Micosis/microbiología , Micosis/fisiopatología , Reproducibilidad de los Resultados , Estudios Retrospectivos
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