The distribution of  ̄(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres( ̄(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scinti...The distribution of  ̄(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres( ̄(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the  ̄(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of  ̄(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of  ̄(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of  ̄(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.展开更多
AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hep...AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.展开更多
AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant...AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.展开更多
AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carc...AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.展开更多
Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixtee...Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B 17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×10^7 cells (0.5 mL) per mouse. The behaviors of mice, tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100% SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P〈0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.展开更多
Objective: To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inocu...Objective: To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors in nude mice by subcutaneous injection. Then the subcutaneous tumors were implanted into the liver of nude mice, and the orthotopic transplantation tumor models of human hepatocellular carcinoma were established. Seventy-five models were randomized into 5 groups ( n = 15) . Bufalin was injected intraperitoneally into the 3 groups at dose of 1.5,1 and 0.5 mg/kg for day 15 - 24, respectively. NS group were injected equal volume saline as above and adriamycin were injected intraperitoneally into ADM group at dose of 8.0 mg/kg for day 15. Ten mice in each group were killed at day 25 and detected on morphological and ultrastructural changes in myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscope. The survival time in each group were observed. Results: The tumor volumes in each group of bufalin were reduced significantly compared with NS group (P < 0.01), the survival time were prolonged in group Bu 1 and Bu 2 compared with NS group ( P < 0.05), and tumor tissues were mainly necrosis in severe or moderate degree in Bu 1, Bu 2 groups, and mild degree or moderate degree in Bu 3 group. No morphological changes were detected in myocardium, brain, liver and kidney tissues, respectively. Apoptotic characteristics could be seen in tumor tissues of group Bu 1 and group Bu 2. Conclusion: Bufalin has significant anti-tumor effects on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice without marked toxicity. To guide cell apoptosis may be one of its anti-tumor mechanism of bufalin.展开更多
Objective: To observe the morphological features of neoplastic cell apoptosis developed in nude mice transplants with nasopharyngeal carcinoma (NPC) cell lines, CNE-1 and CNE-2, and to investigate the roles of p53, bc...Objective: To observe the morphological features of neoplastic cell apoptosis developed in nude mice transplants with nasopharyngeal carcinoma (NPC) cell lines, CNE-1 and CNE-2, and to investigate the roles of p53, bcl-2 and bax playing in the process of apoptosis. Methods: CNE-1 and CNE-2 cell lines were inoculated and passed in nude mice for 3 generations. The cell apoptosis was detected on H & E and TUNEL staining slides. The expression of p53, bcl-2 and bax were detected by using immunohistochemistry. p53 gene alteration was assayed in cell lines and transplants by PCR-SSCP. Results: A considerable number of neoplastic cells underwent apoptosis in CNE-1 and CNE-2 transplant tissues. The “shrinkage necrosis” and apoptotic bodies were the main appearances of apoptosis. The p53 alteration was detected in exon 8 by PCR-SSCP and p53 protein accumulation observed in the cell smears and nude mice transplant tissue sections. All the transplant tissue sections of 3 passages showed bcl-2 negativity and bax overexpression. Conclusion: The neoplastic cells of CNE-1 and CNE-2 transplants underwent death mainly taking the way of apoptosis. The “shrinkage necrosis” and apoptotic bodies were the main morphological features of apoptosis seen in those transplants. The apoptosis in CNE-1 or CNE-2 nude mice transplant is highly probable through a p53-independent and bax-mediated pathway.展开更多
Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem (ES) cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line...Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem (ES) cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.展开更多
The effect of treatment with Chinese medicine including Salvia miltiorrhizan and Astragalus, and the nonsteroid anti-inflammatory drug aspirin alone or combining radiotherapy, was investigated in 6-8 week-old TA2 mice...The effect of treatment with Chinese medicine including Salvia miltiorrhizan and Astragalus, and the nonsteroid anti-inflammatory drug aspirin alone or combining radiotherapy, was investigated in 6-8 week-old TA2 mice being inoculated mammary carcinoma. The date indicated the following conclusions: the tumor growth could be inhibited by aspirin alone (p<0.01) but Chinese medicine group was observed. Mice treated with radiotherapy together with medicine both Chinese medicine and aspirin, had a statistically significant tumor inhibiting (p<0.01) as compared to mice treated with radiotherapy alone. The function to prevent the normal tissues from radiation by these two medicine groups were observed simultaneously. In addition, blood-flow volume of microcirculation, immune function and lymphocyte micronucleus were examined, which were used to analyse potential mechanism of sensitizing enhancement for Chinese medicine and aspirin.展开更多
A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained i...A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.展开更多
By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of ...By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.展开更多
Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like m...Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.展开更多
Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The ...Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The immune preventative and immnotherapeutic effects of DC vaccines on mice with pancreatic carcinoma were assessed. Results After vaccination of the DC vaccines,mice remained tumor-free for at least 25 days in DCs vaccines group,but in other groups the subcutaneous implantation tumorigenesis were found beginning 3 to 9 days. CTL stimulated by DC vaccines effected cytolytic activity against pancreatic carcinoma cells. The survival period was obviously prolonged in DCs vaccines group (56 ±9)d than in other groups P【0.01) and tumors (1.4 ±0.8)g in DCs vaccines group were significantly smaller than that in other groups (P 【 0. 05). Conclusion Tumor cell lysate-pulsed dendrtic cells vaccines can induce a specific and effective immune response against pancreatic carcinoma cell implanted in mice.展开更多
Objective To establish a SOI model of human renal carcinoma and a high metastatic cell subline. Methods A human renal cell line RCC-9863 has been established by inoculating a human renal tumor tissue into nude mice s....Objective To establish a SOI model of human renal carcinoma and a high metastatic cell subline. Methods A human renal cell line RCC-9863 has been established by inoculating a human renal tumor tissue into nude mice s. c.. When RCC-9863 passaged for 20 times, the tissue from the same xemotransplant tumor were used to construct SOI model. Cultured the metastatic tissue in vitro, the tumor cell suspension was then injected orthotopically, The metastatic tissue obtained underwent the same procedure again. At last, the metastatic tumor was cultured in vitro and cloned. Results 15 days later, a tumor mass sized 1. 7 cm × 0. 6 cm in the nude mouse’s renal parenchyma was grown which lobulated, rude, and with multiply blood vessels and 55 days later later the mouse became moribund and metastases in the lungs were formed. The transplanted renal tumor in the SOI model grew fast and invasively and metastasized to lungs, lymphatic node and liver. A subline, MRCC, with metastatic ability to the lung was selected.展开更多
AIM To establish a method of labeling anti hepatoma McAb (HAb18) Fab fragment modifier with 99m Tc. METHODS HAb18 Fab was modified with 2 iminotholane and labeled with 99m Tc by transchelation f...AIM To establish a method of labeling anti hepatoma McAb (HAb18) Fab fragment modifier with 99m Tc. METHODS HAb18 Fab was modified with 2 iminotholane and labeled with 99m Tc by transchelation from 99m Tc GH. Labeling yield, radiochemical purity and immunoreactivity were determined by thin layer chromatography (TLC SG), paper chromatography (PC), gel chromatography (GC) and cell binding assay, respectively. The nude mice bearing human hepatoma were used for radioimmunoimaging (RII). RESULTS A radiolabeling yield of 50%-80% was obtained, and immunoreactivity (IR) was 30%-40%. Radioimaging results showed that 99m Tc HAb18 McAb Fab fragment was concentrated in the tumor 4-8 hours after injection, and the maximum concentration was seen in 12-24 hours, and the T/NT value was 5 18 and 7 48 at 6h and 8h after the injection. CONCLUSION 99m Tc HAb18 McAb Fab fragment could be specifically localized in the tumor of nude mice bearing human hepatocellular carcinoma within 24 hours and this method might be effectively used for labeling McAb Fab fragment with展开更多
Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,A...Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,Azadirachla.Feroniai has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss alliino mice.Among them as EuE showed maximum capability,the whole study has been conducted with EuE only. Important parameters viz.enhancement of life span,reduction of average tumor weight etc.have been studied.In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured.Effect of EuE on normal peritoneal cells has also been studied.Results:EuE reduced tumor burden remarkably.It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably.It reversed back the hematological parameters towards normal,reduced the Irasplanlability of EAC cells and enhanced the immunomodulatory effects in mice.The host toxic effect of EuE in mice is minimum and mostly reversible with time.All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg(i.p.).Conclusions:The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches.展开更多
INTRODUCTIONHepatocellular carcinoma(HCC)is one of the major causes of death in the word.The mechanism of carcinogenesis is unknown,although it is widely accepted that HBV and HCV are clsely related to liver cancer[1-...INTRODUCTIONHepatocellular carcinoma(HCC)is one of the major causes of death in the word.The mechanism of carcinogenesis is unknown,although it is widely accepted that HBV and HCV are clsely related to liver cancer[1-5[1-5].Previously,a variety of studies have described the differences in gene expression which distinguished tumor from nontumor[6-11].Cloning of the genes,especially the genes associated with HBV and HCV,is still very important to account for the development of liver cancer.展开更多
Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several model...Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore;olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.展开更多
AIM: To investigate genistein-induced apoptosis of implanted tumors of SG7901 cells in nude mice, and the relationship between this apoptosis and expression of Bcl-2 and Bax. METHODS: Establishing a transplanted tum...AIM: To investigate genistein-induced apoptosis of implanted tumors of SG7901 cells in nude mice, and the relationship between this apoptosis and expression of Bcl-2 and Bax. METHODS: Establishing a transplanted tumor model by injecting human SG7901 cells into subcutaneous tissue of nude mice. Genistein (0.5, 1 and 1.5 mg/kg) was directly injected adjacent to the tumor, six times at 2-d intervals. Then, changes in tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphological alterations by transmission electron microscopy (TEN), measured the apoptotic rate by the TUNEL staining method, and detected the expression of apoptosisregulated gene Bcl-2 and bax by immunohistochemical staining and RT-PCR. RESULTS: Genistein 0.5, 1 and 1.5 mg/kg significantly inhibited carcinoma growth when it was injected near the tumor by 10.8%, 29.9% and 39.6%, respectively. Genistein induced implanted tumor cells to undergo apoptosis, with apoptotic characteristics seen by TEM. The apoptosis index was increased progressively with increasing genistein dose (28.9% ± 1.2%, 33.8% ±1.6% and 37.7% ±1.2%). The positive rate of Bcl-2 protein was decreased progressively (11.9%± 0.9%, 5.9%± 0.7% and 4.2% ±0.6%), and the positive rate of bax protein was increased progressively (0.9% ±1.7%, 24.9% ±0.8% and 29.6% ± 1.7%) by immunohistochemical staining, with increasing dose of genistein. The density of Bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT-PCR. CONCLUSION: Genistein was able to induce apoptosisof transplanted tumor cells. This apoptosis may be mediated by down-regulation of the apoptosis-regulated gene Bcl-2 and up-regulation of apoptosis-regulated gene bax.展开更多
Background: Production of chimeric mice is a useful tool for the elucidation of gene function. After successful isolation of embryonic stem (ES) cell lines, there are many methods for producing chimeras, including ...Background: Production of chimeric mice is a useful tool for the elucidation of gene function. After successful isolation of embryonic stem (ES) cell lines, there are many methods for producing chimeras, including co-culture with the embryos, microinjection of the ES ceils into pre-implantation embryos, and use of tetraploid embryos to generate the full ES-derived transgenic mice. Here, we aimed to generate the transgenic ES cell line, compare the production efficiency of chimeric mice and its proportion to yield the male chimeric mice by microinjected ES cells into 4- to 8-cell and blastocysts embryos with the application of Piezo-Micromanipulator (PMM), and trace the fate of the injected ES cells. Results: We successfully generated a transgenic ES cell line and proved that this cell line still maintained pluripotency. Although we achieved a satisfactory chimeric mice rate, there was no significant difference in the production of chimeric mice using the two different methods, but the proportion of the male chimeric mice in the 4- to 8-cell group was higher than in the blastocyst group. We also found that there was no tendency for ES cells to aggregate into the inner cell mass using in vitro culture of the chimeric embryos, indicating that they aggregated randomly. Conclusions: These results showed that the PMM method is a convenient way to generate chimeric mice and microinjection of ES cells into 4- to 8-cell embryos can increase the chance of yielding male chimeras compared to the blastocyst injection. These results provide useful data in transgenic research mediated by ES cells.展开更多
文摘The distribution of  ̄(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres( ̄(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the  ̄(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of  ̄(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of  ̄(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of  ̄(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.
文摘AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.
文摘AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.
基金Supported by National Natural Science Foundation of China, No.81201963Inner Mongolia Natural Science Foundation of China,No.2010MS1123
文摘AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.
基金This work was supported by a grant from the Science & Technology Research Project, Public Health Department of Hebei Province (No. 2003/03086)
文摘Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B 17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×10^7 cells (0.5 mL) per mouse. The behaviors of mice, tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100% SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P〈0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.
基金Supported by National Natural Science Foundation of China (No.30200364)
文摘Objective: To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors in nude mice by subcutaneous injection. Then the subcutaneous tumors were implanted into the liver of nude mice, and the orthotopic transplantation tumor models of human hepatocellular carcinoma were established. Seventy-five models were randomized into 5 groups ( n = 15) . Bufalin was injected intraperitoneally into the 3 groups at dose of 1.5,1 and 0.5 mg/kg for day 15 - 24, respectively. NS group were injected equal volume saline as above and adriamycin were injected intraperitoneally into ADM group at dose of 8.0 mg/kg for day 15. Ten mice in each group were killed at day 25 and detected on morphological and ultrastructural changes in myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscope. The survival time in each group were observed. Results: The tumor volumes in each group of bufalin were reduced significantly compared with NS group (P < 0.01), the survival time were prolonged in group Bu 1 and Bu 2 compared with NS group ( P < 0.05), and tumor tissues were mainly necrosis in severe or moderate degree in Bu 1, Bu 2 groups, and mild degree or moderate degree in Bu 3 group. No morphological changes were detected in myocardium, brain, liver and kidney tissues, respectively. Apoptotic characteristics could be seen in tumor tissues of group Bu 1 and group Bu 2. Conclusion: Bufalin has significant anti-tumor effects on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice without marked toxicity. To guide cell apoptosis may be one of its anti-tumor mechanism of bufalin.
基金a grant from the National Natural Science Foundation of China!(No. 39730200-II)
文摘Objective: To observe the morphological features of neoplastic cell apoptosis developed in nude mice transplants with nasopharyngeal carcinoma (NPC) cell lines, CNE-1 and CNE-2, and to investigate the roles of p53, bcl-2 and bax playing in the process of apoptosis. Methods: CNE-1 and CNE-2 cell lines were inoculated and passed in nude mice for 3 generations. The cell apoptosis was detected on H & E and TUNEL staining slides. The expression of p53, bcl-2 and bax were detected by using immunohistochemistry. p53 gene alteration was assayed in cell lines and transplants by PCR-SSCP. Results: A considerable number of neoplastic cells underwent apoptosis in CNE-1 and CNE-2 transplant tissues. The “shrinkage necrosis” and apoptotic bodies were the main appearances of apoptosis. The p53 alteration was detected in exon 8 by PCR-SSCP and p53 protein accumulation observed in the cell smears and nude mice transplant tissue sections. All the transplant tissue sections of 3 passages showed bcl-2 negativity and bax overexpression. Conclusion: The neoplastic cells of CNE-1 and CNE-2 transplants underwent death mainly taking the way of apoptosis. The “shrinkage necrosis” and apoptotic bodies were the main morphological features of apoptosis seen in those transplants. The apoptosis in CNE-1 or CNE-2 nude mice transplant is highly probable through a p53-independent and bax-mediated pathway.
文摘Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem (ES) cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.
文摘The effect of treatment with Chinese medicine including Salvia miltiorrhizan and Astragalus, and the nonsteroid anti-inflammatory drug aspirin alone or combining radiotherapy, was investigated in 6-8 week-old TA2 mice being inoculated mammary carcinoma. The date indicated the following conclusions: the tumor growth could be inhibited by aspirin alone (p<0.01) but Chinese medicine group was observed. Mice treated with radiotherapy together with medicine both Chinese medicine and aspirin, had a statistically significant tumor inhibiting (p<0.01) as compared to mice treated with radiotherapy alone. The function to prevent the normal tissues from radiation by these two medicine groups were observed simultaneously. In addition, blood-flow volume of microcirculation, immune function and lymphocyte micronucleus were examined, which were used to analyse potential mechanism of sensitizing enhancement for Chinese medicine and aspirin.
文摘A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.
文摘By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.
基金Partly supporled by the State Key Basic Research Program Grant of China(G1998051211)Leading Speciality Grant of Shanghai Health Bureau.
文摘Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
文摘Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The immune preventative and immnotherapeutic effects of DC vaccines on mice with pancreatic carcinoma were assessed. Results After vaccination of the DC vaccines,mice remained tumor-free for at least 25 days in DCs vaccines group,but in other groups the subcutaneous implantation tumorigenesis were found beginning 3 to 9 days. CTL stimulated by DC vaccines effected cytolytic activity against pancreatic carcinoma cells. The survival period was obviously prolonged in DCs vaccines group (56 ±9)d than in other groups P【0.01) and tumors (1.4 ±0.8)g in DCs vaccines group were significantly smaller than that in other groups (P 【 0. 05). Conclusion Tumor cell lysate-pulsed dendrtic cells vaccines can induce a specific and effective immune response against pancreatic carcinoma cell implanted in mice.
文摘Objective To establish a SOI model of human renal carcinoma and a high metastatic cell subline. Methods A human renal cell line RCC-9863 has been established by inoculating a human renal tumor tissue into nude mice s. c.. When RCC-9863 passaged for 20 times, the tissue from the same xemotransplant tumor were used to construct SOI model. Cultured the metastatic tissue in vitro, the tumor cell suspension was then injected orthotopically, The metastatic tissue obtained underwent the same procedure again. At last, the metastatic tumor was cultured in vitro and cloned. Results 15 days later, a tumor mass sized 1. 7 cm × 0. 6 cm in the nude mouse’s renal parenchyma was grown which lobulated, rude, and with multiply blood vessels and 55 days later later the mouse became moribund and metastases in the lungs were formed. The transplanted renal tumor in the SOI model grew fast and invasively and metastasized to lungs, lymphatic node and liver. A subline, MRCC, with metastatic ability to the lung was selected.
文摘AIM To establish a method of labeling anti hepatoma McAb (HAb18) Fab fragment modifier with 99m Tc. METHODS HAb18 Fab was modified with 2 iminotholane and labeled with 99m Tc by transchelation from 99m Tc GH. Labeling yield, radiochemical purity and immunoreactivity were determined by thin layer chromatography (TLC SG), paper chromatography (PC), gel chromatography (GC) and cell binding assay, respectively. The nude mice bearing human hepatoma were used for radioimmunoimaging (RII). RESULTS A radiolabeling yield of 50%-80% was obtained, and immunoreactivity (IR) was 30%-40%. Radioimaging results showed that 99m Tc HAb18 McAb Fab fragment was concentrated in the tumor 4-8 hours after injection, and the maximum concentration was seen in 12-24 hours, and the T/NT value was 5 18 and 7 48 at 6h and 8h after the injection. CONCLUSION 99m Tc HAb18 McAb Fab fragment could be specifically localized in the tumor of nude mice bearing human hepatocellular carcinoma within 24 hours and this method might be effectively used for labeling McAb Fab fragment with
基金Supported by University Grant Commission,Dhaka,Bangladeshfor JA Khanam(Grant No.(676)UCC/Chemistry/(10)2007-2008/3269)
文摘Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,Azadirachla.Feroniai has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss alliino mice.Among them as EuE showed maximum capability,the whole study has been conducted with EuE only. Important parameters viz.enhancement of life span,reduction of average tumor weight etc.have been studied.In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured.Effect of EuE on normal peritoneal cells has also been studied.Results:EuE reduced tumor burden remarkably.It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably.It reversed back the hematological parameters towards normal,reduced the Irasplanlability of EAC cells and enhanced the immunomodulatory effects in mice.The host toxic effect of EuE in mice is minimum and mostly reversible with time.All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg(i.p.).Conclusions:The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches.
文摘INTRODUCTIONHepatocellular carcinoma(HCC)is one of the major causes of death in the word.The mechanism of carcinogenesis is unknown,although it is widely accepted that HBV and HCV are clsely related to liver cancer[1-5[1-5].Previously,a variety of studies have described the differences in gene expression which distinguished tumor from nontumor[6-11].Cloning of the genes,especially the genes associated with HBV and HCV,is still very important to account for the development of liver cancer.
文摘Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore;olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.
文摘AIM: To investigate genistein-induced apoptosis of implanted tumors of SG7901 cells in nude mice, and the relationship between this apoptosis and expression of Bcl-2 and Bax. METHODS: Establishing a transplanted tumor model by injecting human SG7901 cells into subcutaneous tissue of nude mice. Genistein (0.5, 1 and 1.5 mg/kg) was directly injected adjacent to the tumor, six times at 2-d intervals. Then, changes in tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphological alterations by transmission electron microscopy (TEN), measured the apoptotic rate by the TUNEL staining method, and detected the expression of apoptosisregulated gene Bcl-2 and bax by immunohistochemical staining and RT-PCR. RESULTS: Genistein 0.5, 1 and 1.5 mg/kg significantly inhibited carcinoma growth when it was injected near the tumor by 10.8%, 29.9% and 39.6%, respectively. Genistein induced implanted tumor cells to undergo apoptosis, with apoptotic characteristics seen by TEM. The apoptosis index was increased progressively with increasing genistein dose (28.9% ± 1.2%, 33.8% ±1.6% and 37.7% ±1.2%). The positive rate of Bcl-2 protein was decreased progressively (11.9%± 0.9%, 5.9%± 0.7% and 4.2% ±0.6%), and the positive rate of bax protein was increased progressively (0.9% ±1.7%, 24.9% ±0.8% and 29.6% ± 1.7%) by immunohistochemical staining, with increasing dose of genistein. The density of Bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT-PCR. CONCLUSION: Genistein was able to induce apoptosisof transplanted tumor cells. This apoptosis may be mediated by down-regulation of the apoptosis-regulated gene Bcl-2 and up-regulation of apoptosis-regulated gene bax.
基金supported by the National Basic Research and Development Program of China(973 ProgramNo.2011CB944202+2 种基金2010CB945001and 2009CB941601)the National Science Supporting Plan of China(2011BAD19B03)
文摘Background: Production of chimeric mice is a useful tool for the elucidation of gene function. After successful isolation of embryonic stem (ES) cell lines, there are many methods for producing chimeras, including co-culture with the embryos, microinjection of the ES ceils into pre-implantation embryos, and use of tetraploid embryos to generate the full ES-derived transgenic mice. Here, we aimed to generate the transgenic ES cell line, compare the production efficiency of chimeric mice and its proportion to yield the male chimeric mice by microinjected ES cells into 4- to 8-cell and blastocysts embryos with the application of Piezo-Micromanipulator (PMM), and trace the fate of the injected ES cells. Results: We successfully generated a transgenic ES cell line and proved that this cell line still maintained pluripotency. Although we achieved a satisfactory chimeric mice rate, there was no significant difference in the production of chimeric mice using the two different methods, but the proportion of the male chimeric mice in the 4- to 8-cell group was higher than in the blastocyst group. We also found that there was no tendency for ES cells to aggregate into the inner cell mass using in vitro culture of the chimeric embryos, indicating that they aggregated randomly. Conclusions: These results showed that the PMM method is a convenient way to generate chimeric mice and microinjection of ES cells into 4- to 8-cell embryos can increase the chance of yielding male chimeras compared to the blastocyst injection. These results provide useful data in transgenic research mediated by ES cells.