Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathoge...Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.展开更多
The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detec...The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the展开更多
This study was designed to evaluate whether the microvascularanastomosis of small arteries and veins in the wound area was possible after gun-shot wound was inflicted to the maxillofacial region of a dog.It was found ...This study was designed to evaluate whether the microvascularanastomosis of small arteries and veins in the wound area was possible after gun-shot wound was inflicted to the maxillofacial region of a dog.It was found thatsmall vessels could be connected with subsequent patency of their lumen if theoperation was performed on the 3rd day after the debridment of the gunshotWound,which provides a basis for microvascular anastomosis to repairmaxillofacial defect due to gunshot wound with free vascularized flap grafting.Inaddition the best time to have a defect repaired and the healing features of thewounds after vascular anastomosis are discussed.展开更多
BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based o...BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.展开更多
BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment ep...BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.展开更多
BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,t...BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and ha...BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.展开更多
The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is th...The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.展开更多
BACKGROUND A gastric stromal tumor(GST)is a mesenchymal tumor that occurs in the gastrointestinal tract;its biological characteristics are highly complex.Clinically,the severity of a GST is often evaluated by factors ...BACKGROUND A gastric stromal tumor(GST)is a mesenchymal tumor that occurs in the gastrointestinal tract;its biological characteristics are highly complex.Clinically,the severity of a GST is often evaluated by factors such as risk classification,tumor size,and mitotic figures.However,these indicators are not very accurate.Even patients classified as low risk are also at risk of metastasis and recurrence.Therefore,more accurate and objective clinical biological behavior evaluations are urgently needed.AIM To determine the relationship between Ki-67 and CD44 expression in GSTs and microvessel formation and prognosis.METHODS Eighty-six GST tissue specimens from our hospital were selected for this study.The immunohistochemical staining technique was used to detect Ki-67,CD44,and microvessel density(MVD)in the collected samples to analyze the different risk grades and mitotic figures.In addition,this approach was used to determine the differences in the expression of Ki-67 and CD44 in GST tissues with varying lesion diameters.RESULTS In GSTs with positive expression of the Ki-67 protein,the proportions of patients with medium-to-high risk and more than five mitotic counts were 24.07%and 38.89%,respectively.In GSTs with positive expression of the CD44 protein,the proportions of patients with medium-to-high risk and more than five mitotic counts were 23.73%and 38.98%,respectively.In GSTs with negative expression of the Ki-67 protein,these values were relatively high(3.70%and 11.11%,respectively).The MVD in GSTs with positive and negative expression of the CD44 protein was 15.92±2.94 and 13.86±2.98/Hp,respectively;the difference between the two groups was significant(P<0.05).CONCLUSION Ki-67 and CD44 expression in GSTs is correlated with the grade of tumor risk and mitotic figures.CD44 expression is correlated with microvessel formation in tumor tissues.展开更多
Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is i...Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.展开更多
AIM: To assess intravoxel incoherent motion diffusionweighted imaging(IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values(0-80...AIM: To assess intravoxel incoherent motion diffusionweighted imaging(IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values(0-800 s/mm2) in 25 human gastric cancer-bearing nude mice at baseline(day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups(n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calciumfolinate treatment. Together with tumor volumes(TV), the apparent diffusion coefficient(ADC) and IVIM parameters [true water molecular diffusion coefficient(D), perfusion fraction(f) and pseudo-related diffusion coefficient(D*)] were measured. The differences in those parameters from baseline to each measurement(ΔTV%, ΔADC%, ΔD%, Δf% and ΔD*%) were calculated. After image acquisition, tumor necrosis, microvessel density(MVD) and cellular apoptosis were evaluated by hematoxylin-eosin(HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed.RESULTS: The observed relative volume increase(ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5(ΔTV_(treatment)% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7(ΔTV_(treatment)% = 29.07% ± 10.01% and ΔTV_(control)% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group(ΔADC%_(treatment), median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group(ΔADC%_(control), median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7(P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group(ΔD%_(treatment), median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group(ΔD%_(control), median-0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5(P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up(median,-34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016;-50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008;-49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and-46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points(median,-32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008;-44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008;-59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and-47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis(r_s = 0.720, P < 0.001; r_s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D(r_s = 0.626, P = 0.001; r_s = 0.542, P = 0.005, respectively). Perfusionrelated parameters(f and D*) were positively correlated to MVD(r_s = 0.618, P = 0.001; r_s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor(r_s =-0.550, P = 0.004; r_s =-0.692, P < 0.001, respectively).CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.展开更多
Abnormal vasculature,termed tumor vessels,is a hallmark of solid tumors.The degree of angiogenesis is associated with tumor aggressiveness and clinical outcome.Therefore,exact quantification of tumor vessels is useful...Abnormal vasculature,termed tumor vessels,is a hallmark of solid tumors.The degree of angiogenesis is associated with tumor aggressiveness and clinical outcome.Therefore,exact quantification of tumor vessels is useful to evaluate prognosis.Furthermore,selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor angiogenesis.Nestin,an intermediate filament protein,is reportedly expressed in repair processes,various neoplasms,and proliferating vascular endothelial cells.Nestin expression is detected in endothelial cells of embryonic capillaries,capillaries of the corpus luteum,which replenishes itself by angiogenesis,and proliferating endothelial progenitor cells,but not in mature endothelial cells.Therefore,expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor cells.Nestin expression is also reported in blood vessels within glioblastoma,prostate cancer,colorectal cancer,and pancreatic cancer,and its expression is more specific for newly formed blood vessels than other endothelial cell markers.Nestin-positive blood vessels form smaller vessels with high proliferation activity in tumors.Knockdown of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in vivo.Using nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic indicator.Furthermore,nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies,including pancreatic cancer.In this review article,we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.展开更多
Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer...Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.展开更多
BACKGROUND:Contrast-enhanced ultrasonography(CEUS) is an important technique for depiction and assessment of tumor vascularity.This study aimed to explore the relationship between the morphological characteristics of ...BACKGROUND:Contrast-enhanced ultrasonography(CEUS) is an important technique for depiction and assessment of tumor vascularity.This study aimed to explore the relationship between the morphological characteristics of tumor microvessels and enhancement patterns on CEUS in hepatocellular carcinoma (HCC). METHODS:Eighty patients with HCC underwent CEUS using SonoVue before hepatectomy.Contrast-enhanced ultrasonographic enhancement patterns and quantitative parameters were recorded.The tumor tissue sections were immunostained with human CD34 monoclonal antibody.The patients were classified into a point-line type group(n=36)and a loop-strip type group(n=44)according to microvessel morphology. The microvascular density(MVD)in the different types of microvessels was calculated.The relationship between enhancement patterns of HCC lesions and morphological characteristics of tumor microvessels was analyzed. RESULTS:The mean MVD in HCC was 22.4±3.5 per 0.2 mm 2 in the point-line group,and 19.6±6.7 per 0.2 mm 2 in the loop-strip group,and there was no significant difference between them(t=0.948,P=0.354).In the portal vein phase, hypoenhancement was significantly more frequent in HCC (χ2=4.789,P=0.029)in the loop-strip group(40/44,90.9%) than in the point-line group(26/36,72.2%).The time to hypoenhancement in the loop-strip group(mean 64.84±26.16 seconds)was shorter than that in the point-line group(mean 78.39±28.72 seconds)(t=2.247,P=0.022).The time to hypoenhancement was correlated with MVD in the loop-strip group(r=-0.648,P=0.001).CONCLUSIONS:The enhancement patterns on CEUS are related to tumor microvascular morphology,and the type of microvascular morphology influences CEUS characterization. CEUS,an important noninvasive imaging technique,is used to evaluate microvascular morphology and angiogenesis,providing valuable information for antiangiogenic therapy in HCC.展开更多
AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study ...AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.展开更多
To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied b...To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied by using immunohistochemical method. Of all the specimens, 20 were obtained from the patients treated with surgical resection alone, 22 from those with second stage surgical resection after TACE. The results showed that the MVD in HCC tissues was 53.4±21 9 in the TACE group and 27.6±9.2 in the single operating group, respectively, with the difference being significant between them ( P <0.001). It was suggested that TACE might contribute to angiogenesis of HCC, possibly due to anoxic stress and ischemia reperfusion injury.展开更多
Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in ...Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer,Methods: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique,The correlation between their expression and the clinicopathologic features was also investigated,Results: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25±1.14 and 25.71%(18/70),The expression value of MVD in colorectal adenocarcinoma tissues was 13.14±3.23,Expression of RUNX3 and MVD value were correlated with CEA,serosal invasion,liver metastasis,lymph node metastasis,and TNM stage(P<0.01),The expression value of RUNX3 had negative correlations with that of MVD,Conclusions: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.展开更多
BACKGROUND:Ischemic recurrent stricture after surgical repair for iatrogenic bile duct injury(BDI)remains a challenge in clinical practice.The present study was designed to investigate whether ischemia is universal an...BACKGROUND:Ischemic recurrent stricture after surgical repair for iatrogenic bile duct injury(BDI)remains a challenge in clinical practice.The present study was designed to investigate whether ischemia is universal and of varied severity at different levels of the proximal bile duct after BDI. METHODS:A total of 30 beagle dogs were randomly divided into control,BDI,and BDI-repaired groups.The BDI animal model was established based on the classic pattern of laparoscopic cholecystectomy-related BDI.The animals were sacrificed on postoperative day 15,and bile duct tissue was harvested to assess microvessel density(MVD)at selected levels of the normal,post-BDI and BDI-repaired bile duct with the CD34 immunohistochemistry technique. RESULTS:In the control group,MVD at level H(high level) was remarkably higher than that at level L(low level).No significant difference was found between MVDs at levels H and M(middle level),as well as at levels M and L.However, the tendency was noted that the closer the level to the hilus, the greater the MVD at that level.In both the BDI and BDI-repaired groups,MVDs at level H were generally greater than those at level L,despite the unremarkable differences between MVDs at neighboring levels.In these two groups,a similar tendency of MVD distribution to that in the control group was found;the closer the level to the injury site,the lower was the MVD at that level.Moreover,compared with the MDVs at the levels M and L in the control group,MVDs at the corresponding levels in the BDI and BDI-repaired groups were all remarkably reduced(P<0.05).In addition,MVDs at all three levels in the BDI group significantly declined further after BDI repair.CONCLUSIONS:After BDI,universal ischemic damage in the injured proximal bile duct develops close to the injury site, while close to the hilus,ischemia is relatively slight.High hepaticojejunostomy,rather than low biloenterostomy or end-to-end duct anastomosis,should be recommended for BDI repair.Great care should be taken to protect the peribiliary plexus during repair.展开更多
Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number...Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.展开更多
Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver ...Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups,which received either normal saline(A),TACE(B),sorafenib(C),sorafenib followed by TACE(D),or TACE followed by sorafenib(E).Serum vascular endothelial growth factor(VEGF)levels were measured before and after TACE via ELISA.Immunohistochemistry for CD34 was performed to evaluate microvessel density(MVD),and ultrasonography was used to access tumor volume.Results:VEGF levels declined in group C but increased significantly on the 3 rd post-operative day in groups B,D,and E.Levels decreased after the 7 th post-operative day.Peak levels were significantly lower in group D than in groups B and E.On the 14 th post-operative day,VEGF levels were the lowest in group C,followed by those in groups D and B.MVD was the lowest in group C followed by that in group D and E,and was the highest in group B.Group D had the smallest tumor volume.HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern,whereas in groups B,D,and E,large areas of tumor cell necrosis were visible.Conclusion:TACE can up-regulate serum VEGF levels,which in turn accelerates the formation of new blood vessels.Thus,TACE combined with sorafenib inhibits VEGF and angiogenesis,and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.展开更多
文摘Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.
文摘The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the
文摘This study was designed to evaluate whether the microvascularanastomosis of small arteries and veins in the wound area was possible after gun-shot wound was inflicted to the maxillofacial region of a dog.It was found thatsmall vessels could be connected with subsequent patency of their lumen if theoperation was performed on the 3rd day after the debridment of the gunshotWound,which provides a basis for microvascular anastomosis to repairmaxillofacial defect due to gunshot wound with free vascularized flap grafting.Inaddition the best time to have a defect repaired and the healing features of thewounds after vascular anastomosis are discussed.
文摘BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.
基金The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
文摘BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.
文摘BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.
文摘The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.
文摘BACKGROUND A gastric stromal tumor(GST)is a mesenchymal tumor that occurs in the gastrointestinal tract;its biological characteristics are highly complex.Clinically,the severity of a GST is often evaluated by factors such as risk classification,tumor size,and mitotic figures.However,these indicators are not very accurate.Even patients classified as low risk are also at risk of metastasis and recurrence.Therefore,more accurate and objective clinical biological behavior evaluations are urgently needed.AIM To determine the relationship between Ki-67 and CD44 expression in GSTs and microvessel formation and prognosis.METHODS Eighty-six GST tissue specimens from our hospital were selected for this study.The immunohistochemical staining technique was used to detect Ki-67,CD44,and microvessel density(MVD)in the collected samples to analyze the different risk grades and mitotic figures.In addition,this approach was used to determine the differences in the expression of Ki-67 and CD44 in GST tissues with varying lesion diameters.RESULTS In GSTs with positive expression of the Ki-67 protein,the proportions of patients with medium-to-high risk and more than five mitotic counts were 24.07%and 38.89%,respectively.In GSTs with positive expression of the CD44 protein,the proportions of patients with medium-to-high risk and more than five mitotic counts were 23.73%and 38.98%,respectively.In GSTs with negative expression of the Ki-67 protein,these values were relatively high(3.70%and 11.11%,respectively).The MVD in GSTs with positive and negative expression of the CD44 protein was 15.92±2.94 and 13.86±2.98/Hp,respectively;the difference between the two groups was significant(P<0.05).CONCLUSION Ki-67 and CD44 expression in GSTs is correlated with the grade of tumor risk and mitotic figures.CD44 expression is correlated with microvessel formation in tumor tissues.
文摘Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.
基金Supported by National Research Foundation of South Korea,No.NRF-2013R1A1A2013878 and No.2015R1A2A2A01007827
文摘AIM: To assess intravoxel incoherent motion diffusionweighted imaging(IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values(0-800 s/mm2) in 25 human gastric cancer-bearing nude mice at baseline(day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups(n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calciumfolinate treatment. Together with tumor volumes(TV), the apparent diffusion coefficient(ADC) and IVIM parameters [true water molecular diffusion coefficient(D), perfusion fraction(f) and pseudo-related diffusion coefficient(D*)] were measured. The differences in those parameters from baseline to each measurement(ΔTV%, ΔADC%, ΔD%, Δf% and ΔD*%) were calculated. After image acquisition, tumor necrosis, microvessel density(MVD) and cellular apoptosis were evaluated by hematoxylin-eosin(HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed.RESULTS: The observed relative volume increase(ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5(ΔTV_(treatment)% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7(ΔTV_(treatment)% = 29.07% ± 10.01% and ΔTV_(control)% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group(ΔADC%_(treatment), median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group(ΔADC%_(control), median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7(P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group(ΔD%_(treatment), median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group(ΔD%_(control), median-0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5(P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up(median,-34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016;-50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008;-49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and-46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points(median,-32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008;-44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008;-59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and-47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis(r_s = 0.720, P < 0.001; r_s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D(r_s = 0.626, P = 0.001; r_s = 0.542, P = 0.005, respectively). Perfusionrelated parameters(f and D*) were positively correlated to MVD(r_s = 0.618, P = 0.001; r_s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor(r_s =-0.550, P = 0.004; r_s =-0.692, P < 0.001, respectively).CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.
基金Supported by Grants-in-Aid forYoung Scientists,No.22689038 (to Matsuda Y)Grants-in-Aid for Challenging Exploratory Research,No.23650604(to Matsuda Y)+1 种基金Grants-in-Aid for Scientific Research,No.22591531(to Ishiwata T) from the Japan Society for the Promotion of Sciencethe Pancreas Research Foundation of Japan(to Hagio M)
文摘Abnormal vasculature,termed tumor vessels,is a hallmark of solid tumors.The degree of angiogenesis is associated with tumor aggressiveness and clinical outcome.Therefore,exact quantification of tumor vessels is useful to evaluate prognosis.Furthermore,selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor angiogenesis.Nestin,an intermediate filament protein,is reportedly expressed in repair processes,various neoplasms,and proliferating vascular endothelial cells.Nestin expression is detected in endothelial cells of embryonic capillaries,capillaries of the corpus luteum,which replenishes itself by angiogenesis,and proliferating endothelial progenitor cells,but not in mature endothelial cells.Therefore,expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor cells.Nestin expression is also reported in blood vessels within glioblastoma,prostate cancer,colorectal cancer,and pancreatic cancer,and its expression is more specific for newly formed blood vessels than other endothelial cell markers.Nestin-positive blood vessels form smaller vessels with high proliferation activity in tumors.Knockdown of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in vivo.Using nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic indicator.Furthermore,nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies,including pancreatic cancer.In this review article,we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.
基金supported by Liaoning BaiQianWan Talents Program(No.2012921017)
文摘Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.
基金supported by grants from the Natural Science Foundation of Hunan Province(10JJ5041)the Medical Research Foundation of Hunan Province(B2010-023),China
文摘BACKGROUND:Contrast-enhanced ultrasonography(CEUS) is an important technique for depiction and assessment of tumor vascularity.This study aimed to explore the relationship between the morphological characteristics of tumor microvessels and enhancement patterns on CEUS in hepatocellular carcinoma (HCC). METHODS:Eighty patients with HCC underwent CEUS using SonoVue before hepatectomy.Contrast-enhanced ultrasonographic enhancement patterns and quantitative parameters were recorded.The tumor tissue sections were immunostained with human CD34 monoclonal antibody.The patients were classified into a point-line type group(n=36)and a loop-strip type group(n=44)according to microvessel morphology. The microvascular density(MVD)in the different types of microvessels was calculated.The relationship between enhancement patterns of HCC lesions and morphological characteristics of tumor microvessels was analyzed. RESULTS:The mean MVD in HCC was 22.4±3.5 per 0.2 mm 2 in the point-line group,and 19.6±6.7 per 0.2 mm 2 in the loop-strip group,and there was no significant difference between them(t=0.948,P=0.354).In the portal vein phase, hypoenhancement was significantly more frequent in HCC (χ2=4.789,P=0.029)in the loop-strip group(40/44,90.9%) than in the point-line group(26/36,72.2%).The time to hypoenhancement in the loop-strip group(mean 64.84±26.16 seconds)was shorter than that in the point-line group(mean 78.39±28.72 seconds)(t=2.247,P=0.022).The time to hypoenhancement was correlated with MVD in the loop-strip group(r=-0.648,P=0.001).CONCLUSIONS:The enhancement patterns on CEUS are related to tumor microvascular morphology,and the type of microvascular morphology influences CEUS characterization. CEUS,an important noninvasive imaging technique,is used to evaluate microvascular morphology and angiogenesis,providing valuable information for antiangiogenic therapy in HCC.
基金Supported by National Natural Science Foundation of ChinaNo.81302123
文摘AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.
文摘To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied by using immunohistochemical method. Of all the specimens, 20 were obtained from the patients treated with surgical resection alone, 22 from those with second stage surgical resection after TACE. The results showed that the MVD in HCC tissues was 53.4±21 9 in the TACE group and 27.6±9.2 in the single operating group, respectively, with the difference being significant between them ( P <0.001). It was suggested that TACE might contribute to angiogenesis of HCC, possibly due to anoxic stress and ischemia reperfusion injury.
基金supported by 2015 Support Project of Science and Technology(152777237)by 2015 Medical Research Project of Health Commission(20150058)by 2013 Mandatory Planning Project of Scientific and Technological Bureau of Zhangjiakou City(1311055D-1)
文摘Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer,Methods: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique,The correlation between their expression and the clinicopathologic features was also investigated,Results: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25±1.14 and 25.71%(18/70),The expression value of MVD in colorectal adenocarcinoma tissues was 13.14±3.23,Expression of RUNX3 and MVD value were correlated with CEA,serosal invasion,liver metastasis,lymph node metastasis,and TNM stage(P<0.01),The expression value of RUNX3 had negative correlations with that of MVD,Conclusions: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.
基金supported by a grant from the Eleventh Five-year Program for Medical Research of the PLA(06MB199)
文摘BACKGROUND:Ischemic recurrent stricture after surgical repair for iatrogenic bile duct injury(BDI)remains a challenge in clinical practice.The present study was designed to investigate whether ischemia is universal and of varied severity at different levels of the proximal bile duct after BDI. METHODS:A total of 30 beagle dogs were randomly divided into control,BDI,and BDI-repaired groups.The BDI animal model was established based on the classic pattern of laparoscopic cholecystectomy-related BDI.The animals were sacrificed on postoperative day 15,and bile duct tissue was harvested to assess microvessel density(MVD)at selected levels of the normal,post-BDI and BDI-repaired bile duct with the CD34 immunohistochemistry technique. RESULTS:In the control group,MVD at level H(high level) was remarkably higher than that at level L(low level).No significant difference was found between MVDs at levels H and M(middle level),as well as at levels M and L.However, the tendency was noted that the closer the level to the hilus, the greater the MVD at that level.In both the BDI and BDI-repaired groups,MVDs at level H were generally greater than those at level L,despite the unremarkable differences between MVDs at neighboring levels.In these two groups,a similar tendency of MVD distribution to that in the control group was found;the closer the level to the injury site,the lower was the MVD at that level.Moreover,compared with the MDVs at the levels M and L in the control group,MVDs at the corresponding levels in the BDI and BDI-repaired groups were all remarkably reduced(P<0.05).In addition,MVDs at all three levels in the BDI group significantly declined further after BDI repair.CONCLUSIONS:After BDI,universal ischemic damage in the injured proximal bile duct develops close to the injury site, while close to the hilus,ischemia is relatively slight.High hepaticojejunostomy,rather than low biloenterostomy or end-to-end duct anastomosis,should be recommended for BDI repair.Great care should be taken to protect the peribiliary plexus during repair.
文摘Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.
基金supported by 2017 Key Research&Development Program of Shaanxi Province,Grant/Award Number:2017SF-095
文摘Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups,which received either normal saline(A),TACE(B),sorafenib(C),sorafenib followed by TACE(D),or TACE followed by sorafenib(E).Serum vascular endothelial growth factor(VEGF)levels were measured before and after TACE via ELISA.Immunohistochemistry for CD34 was performed to evaluate microvessel density(MVD),and ultrasonography was used to access tumor volume.Results:VEGF levels declined in group C but increased significantly on the 3 rd post-operative day in groups B,D,and E.Levels decreased after the 7 th post-operative day.Peak levels were significantly lower in group D than in groups B and E.On the 14 th post-operative day,VEGF levels were the lowest in group C,followed by those in groups D and B.MVD was the lowest in group C followed by that in group D and E,and was the highest in group B.Group D had the smallest tumor volume.HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern,whereas in groups B,D,and E,large areas of tumor cell necrosis were visible.Conclusion:TACE can up-regulate serum VEGF levels,which in turn accelerates the formation of new blood vessels.Thus,TACE combined with sorafenib inhibits VEGF and angiogenesis,and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.
