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ABSTRACT: Fish are noted for their excellent performances to cruise efficiently, to maneuver and to position themselves accurately. These performances are the result of complex 3D motion and the cooperation of different fins of fish. In this paper, we focus on the research of the pectoral fin, and present a novel mechanical design of flexible pectoral fin capable of 3D undulation, actuated by shape memory alloy (SMA). First, we implement a detailed design of flexible pectoral fin which is composed of a series of SMA fin rays. Each fin ray consists of two serial installed SMA plate couples and is capable of bending in two mutually orthogonal directions. Second, we analyze the energy distribution of the response process of the SMA plate couple from the aspect of thermodynamics, meanwhile, we conduct a thermodynamics simulation to research the response process. Third, the control system is designed to obtain the accurate control of the locomotion of the fin ray. Finally, we conduct experiments to investigate the performance of the SMA fin ray and attain the following results: (a) relationship between temperature and actuation time; (b) relationship between angular displacement and time; (c) relationship between torque and current. The experimental results show that SMA driven fin ray has a good performance and that the SMA driven flexible pectoral fin can be well achieved.
Robotics and Biomimetics (ROBIO), 2009 IEEE International Conference on; 01/2010
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ABSTRACT: We present experimental velocity, propulsion force and power measurements finding out that the significance level of shape and kinematics parameters of robotic fin to its propulsion performance. The data have been obtained through synchronous velocity, propulsive force and the power measurements on an undulatory robotic fin mechanism, at the Reynolds numbers 10<sup>6</sup>. The lateral motion of the robotic fin is in the form of a travelling wave, the kinematics parameters we investigated are frequency, amplitude, wavelength and envelope line. According to the data of velocity, propulsive force and the power measurements, the propulsion efficiency can be conducted. The experimental result indicates that the velocity, propulsive force and propulsion efficiency is optimum with the fin shape is isosceles trapezoid, the frequency and amplitude of fluctuation is 1.67Hz and 100 mm respectively. The optimization result is meaningful for the mechanical design of undulatory fin propulsion.
Robotics and Biomimetics (ROBIO), 2009 IEEE International Conference on; 01/2010
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ABSTRACT: The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay. CONCLUSION: The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern in vivo and in a three-dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.
Hepatology 09/2009; 51(2):545-56. · 11.66 Impact Factor
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ABSTRACT: To explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor.
A total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM.
Totally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04).
Vasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.
Zhonghua bing li xue za zhi Chinese journal of pathology 09/2009; 38(9):585-9.
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ABSTRACT: To investigate the influence of different microenvironments on melanoma vasculogenic mimicry, invasiveness and metastasis behavior.
It was an experimental study. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. The invasion and metastasis were observed. EphA2, MMP-2 and MMP-9 expression and their mRNA levels were detected by immunohistochemical staining and real time RT-PCR and compared between two groups.
Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of VM channels was significantly higher in subretinal group (t = 4. 188, P = 0.000). However, no significant difference of mosaic vessel and endothelium-dependent vessel was observed between two groups (t = 1.473, 1.805; P = 0.146, 0.076, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group (data not shown). The mRNA levels of EphA2, MMP-2 and MMP-9 were rather higher in the subretinal tumor (t = 3.642, 8.109, 9.357; P = 0.002, 0.001 and 0.001, respectively). There was a positive association in melanoma cells of the VM between expression of EphA2 (r = 0.412, P = 0.021) but no statistically significant correlation between VM and MMP-2 (P > 0.05), nor between VM and MMP-9.
Different microenvironments affect invasiveness and blood supply patterns of melanoma. Melanoma cells in intraocular microenvironment increased EphA2 expression which induced the formation of VM channels. Moreover, the expression of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness and metastasis behavior.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 07/2009; 45(7):641-6.
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ABSTRACT: To study the correlation between the expression of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF) and vasculogenic mimicry (VM) in gastrointestinal stromal tumors (GIST).
The immunohistochemical staining indices (SI) of MMP-2, MMP-9, VEGF were assessed on specimens of 84 human cases with GIST (21 VM-positive cases). Gelatin zymography analysis of the activity of MMP-2 and MMP-9 activities were performed on another 42 human cases of GIST with fresh tissue (22 VM-positive cases).
The staining indices (SI) of MMP-2 and MMP-9 were higher in the VM-positive group (4.10 +/- 2.05 and 3.43 +/- 1.89 respectively) than in the VM-negative group (2.98 +/- 1.97 and 2.38 +/- 1.84 respectively, both P < 0.05); there was no statistic difference in the SI of VEGF between VM-positive and VM-negative group. Gelatin zymography analysis showed that the activity of MMP-2 and MMP-9 were significantly higher in the VM-positive group (3.62 +/- 3.95 and 4.77 +/- 5.29 respectively) than in the VM-negative group (1.26 +/- 1.21 and 2.11 +/- 1.54 respectively, both P < 0.05).
The expression of MMP-2 and MMP-9 correlates with VM formation in GIST.
Zhonghua yi xue za zhi 04/2009; 89(16):1106-9.
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ABSTRACT: To establish a method of SYT-SSX fusion gene detection by FISH and to explore its diagnostic value for synovial sarcoma.
The presence of SYT-SSX fusion gene was determined by FISH using a tissue microarray containing 62 known synovial sarcomas, 60 non-synovial sarcomas and 133 equivocal synovial sarcomas. FISH results were compared with those of RT-PCR published previously.
Overall, 96.9% (247/255) of the cases were successfully analyzed by FISH. The sensitivity of FISH for known synovial sarcomas was 96.7% (58/60), and the specificity for the non-synovial sarcoma was 100% (59/59). Moreover, SYT-SSX gene fusion was detected in 78.1% (100/128) of the equivocal synovial sarcomas. The concordance rate between FISH and RT-PCR was 83.6% (102/122) in those equivocal synovial sarcomas, and overall 79.7% (106/133) of these cases were confirmed as synovial sarcomas either by RT-PCR or by FISH.
The sensitivity and specificity of FISH detection of SYT-SSX fusion gene are high. FISH and RT-PCR are complementary to each other in the confirmation of synovial sarcomas, particularly those questionable cases.
Zhonghua bing li xue za zhi Chinese journal of pathology 11/2008; 37(10):660-4.
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ABSTRACT: Ovarian cancer is a silent killer, and shows early extensive tumor invasion and peritoneal metastasis. The microcirculation of most tumors includes cooperation of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis and vasculogenic mimicry (VM). VM is critical for a tumor blood supply and is asscociated with aggressive features and metastasis. Our studies highlight the plasticity of aggressive human ovarian carcinoma cells and call into question the underlying significance of their ability to form VM in vitro induced by VEGF-a. These studies also show their clinicalpathological features of the cancers with human Paraffin-embedded tumor tissue samples. Results show that the process: VEGF-a-->EphA2-->MMPs-->VM is the main pathway for VM formation and VEGF-a appears to play an important role in the formation of VM based on our in vitro assays and clinical immunohistochemical analyses. VM-targeting strategies for ovarian cancer include anti-VEGF-a treatment, knocking down the EphA2 gene and using antibodies against human MMPs if the tumor is VM positive. This strategy may be of significant value in laying the foundation for a more explicit anti-tumor angiogenesis therapy.
Cancer biology & therapy 03/2008; 7(5):758-66. · 2.64 Impact Factor
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ABSTRACT: To investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability.
Melanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments.
CK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively.
Different microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.
Zhonghua bing li xue za zhi Chinese journal of pathology 01/2008; 36(12):832-7.
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Zhonghua bing li xue za zhi Chinese journal of pathology 11/2007; 36(10):694-7.
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ABSTRACT: To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.
To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.
Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.
The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 08/2007; 29(7):500-4.
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ABSTRACT: To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth.
A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining.
Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2, MMP-9, TIMP-2 in each treatment group were statistically different from their control groups (F = 12.79, F = 5.56, F = 4.64; P < 0.05).
Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.
Zhonghua bing li xue za zhi Chinese journal of pathology 12/2006; 35(11):677-80.
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Zhonghua bing li xue za zhi Chinese journal of pathology 12/2006; 35(11):698-9.
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ABSTRACT: To explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.
Ninety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.
12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).
VM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 02/2006; 14(1):41-4.
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ABSTRACT: Many fishes use undulatory fin to propel themselves in the underwater environment. These locomotor mechanisms have a popular
interest to many researchers. In the present study, we perform a three-dimensional unsteady computation of an undulatory mechanical
fin that is driven by Shape Memory Alloy (SMA). The objective of the computation is to investigate the fluid dynamics of force
production associated with the undulatory mechanical fin. An unstructured, grid-based, unsteady Navier-Stokes solver with
automatic adaptive remeshing is used to compute the unsteady flow around the fin through five complete cycles. The pressure
distribution on fin surface is computed and integrated to provide fin forces which are decomposed into lift and thrust. The
velocity field is also computed throughout the swimming cycle. Finally, a comparison is conducted to reveal the dynamics of
force generation according to the kinematic parameters of the undulatory fin (amplitude, frequency and wavelength).
International Journal of Automation and Computing 01/2006; 3(4):374-381.
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ABSTRACT: To explore the expression and significance of E-cadherin (E-cad) and beta-catenin (beta-cat) in synovial sarcoma.
Expression of E-cad and beta-cat in 72 cases of synovial sarcoma were detected by tissue microarray technique and immunohistochemistry. The relationships between E-cad and beta-cat expression and clinicopathological data and survival rate were analyzed.
(1) 95.1% of dots on the tissue microarrays were observable morphologically. The background was clear and the contrast was vivid after immunohistochemistry. (2) The expression of E-cad was reduced in 56 patients (77.8%) and that of beta-cat was reduced in 51 patients (70.8%). (3) In patients with synovial sarcoma of monophasic fibrous type, grade III, and in patients with recurrence or metastasis, CK-negative and EMA-negative the rates of reduced expression of E-cad and beta-cat were significantly higher than those with primary sarcoma of biphasic type, grade II, CK-positive and EMA positive (P < 0.05 for all). (4) The survival of synovial sarcoma patients with E-cad and beta-cat expressions preserved was significantly better than those with reduced expressions (P = 0.012, P = 0.047).
The expression of E-cad and beta-cat is correlated with cell differentiation. Reduced expression of E-cad and beta-cat may indicate a high potential of recurrence or metastasis and poor prognosis. Tissue microarray technique is applicable for retrospective studies of large sample size.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 12/2005; 27(12):727-30.
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ABSTRACT: To study the effect of sulindac on colon cancer induction in mice.
The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena.
Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H = 33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet.
Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.
World Journal of Gastroenterology 06/2005; 11(18):2822-6. · 2.47 Impact Factor
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Xishan Hao,
Baocun Sun,
Limei Hu,
Harri Lähdesmäki,
Valerie Dunmire,
Yumei Feng, Shi-Wu Zhang,
Huamin Wang,
Chunlei Wu,
Hua Wang,
Gregory N Fuller,
W Fraser Symmans,
Ilya Shmulevich,
Wei Zhang
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ABSTRACT: Metastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step in the metastatic process.
To gain insight into the molecular events that underlie breast carcinoma metastasis, the authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and metastases after screening for enrichment of tumor cells. Statistical analysis identified genes that are expressed at elevated or decreased levels in metastases relative to the corresponding primary tumors. Multidimensional scaling analysis indicated that in terms of expression levels, primary tumors were tightly clustered, whereas metastases exhibited a greater spread; this finding points to the more heterogeneous nature of metastases. Among the differentially expressed entities were the invasion- and tissue modeling-related genes IGFBP5, fibronectin, and MMP2; the cell cycle regulatory gene cyclin D1; other genes, such as enolase 2; and an expressed sequence tag similar to angiopoietin 1. To validate and extend these initial findings, the authors constructed a tissue microarray consisting of 100 primary malignancies paired with their lymph node metastases. Antibodies for the IGFBP-5, fibronectin, MMP-2, cyclin D1, and MDM-2 proteins were used to stain tissue array sections.
Consistent with microarray data, statistically significant overexpression of IGFBP-5, down-regulation of cyclin D1, and unchanged MDM-2 levels were observed in metastatic tumor cells. Nonetheless, although fibronectin and MMP2 mRNA expression levels were decreased in many metastasis specimens, expression levels of the corresponding proteins in the extracellular matrix were elevated in most metastases. Decreased expression of fibronectin and MMP2 in lymph node metastases was further confirmed by real-time polymerase chain reaction assays performed on five additional specimen pairs.
The results of the current study suggest that extracellular matrix protein expression and nuclear gene expression are associated via a negative-feedback regulatory mechanism. Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process.
Cancer 04/2004; 100(6):1110-22. · 4.77 Impact Factor
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ABSTRACT: To investigate the mode of angiogenesis between highly invasive malignant melanoma and poorly invasive malignant melanoma by immunohistochemistry and periodic acid-Schiff stain (PAS) and to discuss whether the tumor cells in highly invasive malignant melanoma carry vasculogenic mimicry through self-metamorphosis, thus acquiring blood supply to sustain their growth.
Thirty cases of highly invasive malignant melanoma and 30 cases of poorly invasive malignant melanoma were retrieved and reprocessed as tissue microarray for further investigations. The tissue microarray sections were then stained with CD34 and PAS; and the positivity rates were compared.
There was a significant difference between CD34 and PAS staining in highly invasive malignant melanoma (P < 0.01). The difference was not statistically significant in poorly invasive malignant melanoma (P > 0.05).
Vasculogenic mimicry exists in some cases of highly invasive malignant melanoma. It is possible that the tumor cells can acquire blood supply to sustain growth and metastasize via this mechanism.
Zhonghua bing li xue za zhi Chinese journal of pathology 12/2003; 32(6):539-43.
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ABSTRACT: To study the relationship between collgen (Col) IV, VEGF secreted by the tumor cells and vasculogenic mimicry (VM).
158 bi-phase differential malignant tumor specimens were alloted and made into tissue microarray. These tissue microarray sections were stained with CD31, periodic acid-Schiff (PAS) and Col IV. Subsequently, distributive trait of Col IV and the difference of VEGF expression were analyzed.
The basement membrane of VM was PAS and Col IV positive. The expression of VEGF in bi-phase differential malignant tumor with VM was less than that in those without VM. The difference of VEGF expression in malignant melanoma and alveolar rhabdomyosarcoma was significant (P < 0.05).
Collgen IV and periodic acid-Schiff positive material take part in constructing the basement membrane of vasculogenic mimicry. The difference of the VEGF expression proves that vasculogenic mimicry can sustain the tumor blood supply.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 12/2003; 25(6):524-6.
