Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer.

Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.

High-resolution dynamic imaging and quantitative analysis of lung cancer xenografts in nude mice using clinical PET/CT.

Considering the general application of dedicated small-animal positron emission tomography/computed tomography is limited, an acceptable alternative in many situations might be clinical PET/CT. To estimate the feasibility of using clinical PET/CT with [F-18]-fluoro-2-deoxy-D-glucose for high-resolution dynamic imaging and quantitative analysis of cancer xenografts in nude mice. Dynamic clinical PET/CT scans were performed on xenografts for 60 min after injection with [F-18]-fluoro-2-deoxy-D-glucose. Scans were reconstructed with or without SharpIR method in two phases. And mice were sacrificed to extracting major organs and tumors, using ex vivo γ-counting as a reference. Strikingly, we observed that the image quality and the correlation between the all quantitive data from clinical PET/CT and the ex vivo counting was better with the SharpIR reconstructions than without. Our data demonstrate that clinical PET/CT scanner with SharpIR reconstruction is a valuable tool for imaging small animals in preclinical cancer research, offering dynamic imaging parameters, good image quality and accurate data quatification.

Inhibition of TRPC6 reduces non-small cell lung cancer cell proliferation and invasion.

Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC.

Combination of three-gene immunohistochemical panel and magnetic resonance imaging-detected extramural vascular invasion to assess prognosis in non-advanced rectal cancer patients.

AIM: To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS: About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS: Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION: These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC.

99mTc-HYNIC-MPG: a novel SPECT probe for targeting mutated EGFR.

Mutated epidermal growth factor receptor (EGFR) is an important biomarker for cancer diagnosis and molecular target for many anticancer drugs. Localizing EGFR and evaluating EGFR mutational status can help to identify patients who are potentially the most suitable ones for targeted treatments. Hence, we developed a novel EGFR tyrosine kinase inhibitor labeled with (99m)Tc ((99m)Tc-HYNIC-MPG) and evaluated its EGFR binding capacity in vitro and in vivo. This molecular probe was synthesized by one-step method that is simple and highly efficient. Importantly, the uptake rate for (99m)Tc-HYNIC-MPG in the liver was as low as 28.44 ± 0.15% (mean ± SD, n=3). This finding presents for the first time that (99m)Tc-HYNIC-MPG can bind to mutated EGFR efficiently and thus provides a novel molecular tool to detect mutated EGFR and suppress tumorigenesis.

Physical activity is associated with elevated arterial stiffness in patients with lumbar disk herniation.

STUDY DESIGN: A cross-sectional study in a general health examination. OBJECTIVE: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Various vascular risk factors such as obesity, diabetes mellitus, and smoking have been reported to be associated with LDH. BaPWV is an early indicator of subclinical atherosclerosis. METHODS: A total of 490 participants with LDH and 490 participants without LDH were selected for the evaluation of baPWV. BaPWV was measured using an automatic device. The prevalence of LDH was calculated by the quartiles of baPWV levels. Multiple linear regression analysis was performed to evaluate the risk factors for baPWV. RESULTS: LDH patients had significantly higher readings of baPWV compared with non-LDH subjects (P<0.001). The prevalence rate of LDH gradually increased according to baPWV quartiles. In addition, the levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis showed that body mass index, low-density lipoprotein cholesterol, physical activity, and systolic blood pressure contributed to increased baPWV. CONCLUSIONS: The findings showed that LDH patients had higher baPWV levels. In addition, reduced physical activity was a risk factor contributing to increased baPWV. Further studies are warranted to determine the role of baPWV in LDH.

Combining Coronary with Carotid and Cerebrovascular Angiography Using Prospective ECG Gating and Iterative Reconstruction with 256-slice CT.

OBJECTIVE: To investigate the image quality and radiation dose of combined coronary and carotid/cerebrovascular angiography with ECG gating and iterative reconstruction using 256-slice CT compared with the findings with the two examinations performed separately. PATIENTS AND METHODS: One hundred sixty-five consecutive patients underwent a single-injection single-pass combination of coronary and carotid/cerebrovascular CT angiography (group A), coronary CT angiography alone (group B), or carotid/cerebrovascular CT angiography alone (group C). We assessed the image quality of the combined and separate examinations and calculated the respective effective radiation doses. We evaluated the differences in the proportions of image quality grade between the combination and single-examination groups. Diagnostic performance of the combined scanning for detecting significant vascular stenosis has been compared with reference digital subtraction angiography (DSA) in the patient subgroup of group A. RESULTS: There was no significant difference in age, body mass index (BMI), or gender distribution among the 3 groups (all P > 0.05). But there was significant difference in scan length, DLP, and effective dose among the 3 groups (all P < 0.05). There were no significant differences in the effective radiation dose of coronary scanning between groups A and B (P > 0.05), while the effective radiation dose of carotid/cerebrovascular scanning in group A was significantly lower than that in group C (P < 0.05), and the total effective radiation dose in group A were relatively low (2.21 ± 1.38 mSv). The differences of the proportion of carotid/cerebrovascular image quality grades between groups A and C were not significant (P > 0.05). In a subgroup of group A of 30 patients with DSA, combined computed tomographic angiography successfully detected 56 coronary stenosis on per-segment basis, and 62 stenosis on carotid and cerebral artery. The sensitivity, specificity, positive and negative predictive value (NPV) of coronary stenosis were 91.80%, 95.60%, 87.50% and 97.21%, respectively. The sensitivity, specificity, positive and NPV of carotid/cerebrovascular stenosis were 93.55%, 94.68%, 92.06% and 95.70%, respectively. CONCLUSION: Combination of coronary and carotid/cerebrovascular angiography with 256-slice CT scanner with prospective ECG gating and iterative reconstruction produces diagnostic-quality images of the coronary, carotid, and cerebrovascular systems in a single examination, using less contrast medium and a lower radiation dose than when the two examinations are performed separately. This novel technique has high accuracy in detecting significant stenosis in one image setting.

Lovastatin-Induced Phosphatidylinositol-4-Phosphate 5-Kinase Diffusion from Microvilli Stimulates ROMK Channels.

We recently showed that lovastatin attenuates cyclosporin A (CsA)-induced damage of cortical collecting duct (CCD) principal cells by reducing intracellular cholesterol. Previous studies showed that, in cell expression models or artificial membranes, exogenous cholesterol directly inhibits inward rectifier potassium channels, including Kir1.1 (Kcnj1; the gene locus for renal outer medullary K(+) [ROMK1] channels). Therefore, we hypothesized that lovastatin might stimulate ROMK1 by reducing cholesterol in CCD cells. Western blots showed that mpkCCDc14 cells express ROMK1 channels with molecular masses that approximate the molecular masses of ROMK1 in renal tubules detected before and after treatment with DTT. Confocal microscopy showed that ROMK1 channels were not in the microvilli, where cholesterol-rich lipid rafts are located, but rather, the planar regions of the apical membrane of mpkCCDc14 cells. Furthermore, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], an activator of ROMK channels, was detected mainly in the microvilli under resting conditions along with the kinase responsible for PI(4,5)P2 synthesis, phosphatidylinositol-4-phosphate 5-kinase, type I γ [PI(4)P5K I γ], which may explain the low basal open probability and increased sensitivity to tetraethylammonium observed here for this channel. Notably, lovastatin induced PI(4)P5K I γ diffusion into planar regions and elevated PI(4,5)P2 and ROMK1 open probability in these regions through a cholesterol-associated mechanism. However, exogenous cholesterol alone did not induce these effects. These results suggest that lovastatin stimulates ROMK1 channels, at least in part, by inducing PI(4,5)P2 synthesis in planar regions of the renal CCD cell apical membrane, suggesting that lovastatin could reduce cyclosporin-induced nephropathy and associated hyperkalemia.

Lovastatin inhibits human B lymphoma cell proliferation by reducing intracellular ROS and TRPC6 expression.

Clinical evidence suggests that statins reduce cancer incidence and mortality. However, there is lack of in vitro data to show the mechanism by which statins can reduce the malignancies of cancer cells. We used a human B lymphoma Daudi cells as a model and found that lovastatin inhibited, whereas exogenous cholesterol (Cho) stimulated, proliferation cell cycle progression in control Daudi cells, but not in the cells when transient receptor potential canonical 6 (TRPC6) channel was knocked down. Lovastatin decreased, whereas Cho increased, the levels of intracellular reactive oxygen species (ROS) respectively by decreasing or increasing the expression of p47-phox and gp91-phox (NOX2). Reducing intracellular ROS with either a mimetic superoxide dismutase (TEMPOL) or an NADPH oxidase inhibitor (apocynin) inhibited cell proliferation, particularly in Cho-treated cells. The effects of TEMPOL or apocynin were mimicked by inhibition of TRPC6 with SKF-96365. Lovastatin decreased TRPC6 expression and activity via a Cho-dependent mechanism, whereas Cho increased TRPC6 expression and activity via an ROS-dependent mechanism. Consistent with the fact that TRPC6 is a Ca(2+)-permeable channel, lovastatin decreased, but Cho increased, intracellular Ca(2+) also via ROS. These data suggest that lovastatin inhibits malignant B cell proliferation by reducing membrane Cho, intracellular ROS, TRPC6 expression and activity, and intracellular Ca(2+).

Relationship between epicardial adipose tissue volume measured using coronary computed tomography angiography and atherosclerotic plaque characteristics in patients with severe coronary artery stenosis.

AIM: To investigate the relationship between epicardial adipose tissue (EAT) volume and coronary plaque composition. METHODS: EAT volume (measured using coronary computed tomography angiography) and coronary plaque characteristics were assessed on a per-segment basis (modified 15-segment American College of Cardiology/American Heart Association classification) in patients with severe coronary artery stenosis. Coronary plaques were classified into four types: 1, calcified plaques; 2, mixed plaques (calcification dominant); 3, mixed plaques (non-calcification dominant); and 4, non-calcified plaques. The gold standard for luminal stenosis was conventional coronary angiography. RESULTS: In 365 patients (mean age 58.7 ± 8.0 years), EAT volume was 169.85 ± 29.94 ml. There were no significant between-group differences in patient characteristics. Statistically significant differences in EAT volume between non-calcified and calcified plaque groups were observed. EAT volume showed a positive correlation with total cholesterol and low-density-lipoprotein cholesterol, and a very weak correlation with age, triglyceride, body mass index and high-density-lipoprotein cholesterol. CONCLUSION: EAT volume was higher in the presence of non-calcified and mixed plaques in patients with ≥50% severe coronary artery stenosis.

Lovastatin attenuates effects of cyclosporine A on tight junctions and apoptosis in cultured cortical collecting duct principal cells.

We used mouse cortical collecting duct principal cells (mpkCCDc14 cell line) as a model to determine whether statins reduce the harmful effects of cyclosporine A (CsA) on the distal nephron. The data showed that treatment of cells with CsA increased transepithelial resistance and that the effect of CsA was abolished by lovastatin. Scanning ion conductance microscopy showed that CsA significantly increased the height of cellular protrusions near tight junctions. In contrast, lovastatin eliminated the protrusions and even caused a modest depression between cells. Western blot analysis and confocal microscopy showed that lovastatin also abolished CsA-induced elevation of both zonula occludens-1 and cholesterol in tight junctions. In contrast, a high concentration of CsA induced apoptosis, which was also attenuated by lovastatin, elevated intracellular ROS via activation of NADPH oxidase, and increased the expression of p47phox. Sustained treatment of cells with lovastatin also induced significant apoptosis, which was attenuated by CsA, but did not elevate intracellular ROS. These results indicate that both CsA and lovastatin are harmful to principal cells of the distal tubule, but via ROS-dependent and ROS-independent apoptotic pathways, respectively, and that they counteract probably via mobilization of cellular cholesterol levels.

High glucose induces podocyte apoptosis by stimulating TRPC6 via elevation of reactive oxygen species.

Podocyte number is significantly reduced in diabetic patients and animal models, but the mechanism remains unclear. In the present study, we found that high glucose induced apoptosis in control podocytes which express transient receptor potential canonical 6 (TRPC6) channels, but not in TRPC6 knockdown podocytes in which TRPC6 was knocked down by TRPC6 silencing short hairpin RNA (shRNA). This effect was reproduced by treatment of podocytes with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Single-channel data from cell-attached, patch-clamp experiments showed that both high glucose and H2O2 activated the TRPC6 channel in control podocytes, but not in TRPC6 knockdown podocytes. Confocal microscopy showed that high glucose elevated ROS in podocytes and that H2O2 reduced the membrane potential of podocytes and elevated intracellular Ca(2+) via activation of TRPC6. Since intracellular Ca(2+) overload induces apoptosis, H2O2-induced apoptosis may result from TRPC6-mediated elevation of intracellular Ca(2+). These data together suggest that high glucose induces apoptosis in podocytes by stimulating TRPC6 via elevation of ROS.

Impaired brachial artery flow-mediated dilation and increased carotid intima-media thickness in rheumatoid arthritis patients.

BACKGROUND: Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are common parameters used for detecting subclinical atherosclerosis. This study compared subclinical atherosclerosis of the carotid and brachial arteries in rheumatoid arthritis (RA) patients and healthy controls using high resolution ultrasonography. We also investigated their correlation with clinical factors and the association between FMD% and CIMT. METHODS: One hundred and two RA patients and 46 age-gender matched healthy controls were included in the study. FMD of the brachial artery and CIMT were measured ultrasonographically. Patients with diabetes mellitus, hypertension, renal failure, history of cardiovascular or cerebrovascular disease were excluded. Subjects who were receiving or used high dose steroids were also excluded. RESULTS: The CIMT was significantly higher in patients than that in the control group ((0.697±0.053) vs. (0.554±0.051) mm, P<0.001), whereas brachial artery FMD% was lower in patients than that in the controls ((5.454±2.653)% vs. (8.477±2.851)%, P<0.001). CIMT was related to age, disease duration, tender and swollen joint score, C-reactive protein, systolic blood pressure and high-density lipoprotein. However, FMD% was only association with systolic blood pressure. There was no significant correlation between CIMT and FMD%. CONCLUSIONS: Compared with the healthy control subjects, RA patients without clinically evident cardiovascular disease had subclinical atherosclerosis in terms of impaired FMD% and increased CIMT. FMD% and CIMT may measure a different stage of subclinical atherosclerosis in RA patients.

Application of CT perfusion imaging to the histological differentiation of adrenal gland tumors.

BACKGROUND: CT perfusion imaging has been used in diagnosis and classification of tumors widely and in assess tumor angiogenesis in some organs. However, there are few reports describing CT perfusion imaging of adrenal gland tumors. OBJECTIVE: This study aimed to evaluate the application of CT perfusion imaging in analysis of angiogenesis in adrenal tumors and in diagnosis of adrenal tumors. PATIENTS AND METHODS: Forty four patients with adrenal gland tumors (26 with adenomas and 18 with nonadenomas) were enrolled in this study. CT scan of adrenal glands was performed with the perfusion of non-ionic contrast medium Ultravist. The obtained images were processed with deconvolution algorithms-based perfusion software and then perfusion parameter maps and values (blood flow, blood volume, mean transit time, and permeability surface-area production) were generated and analyzed respectively. RESULTS: Univariate multivariate logistic regression indicated that blood volume (OR: 1.261, 95% CI: 1.056, 1.505, P=0.010) was associated with the likelihood of adrenal adenoma. Receiver operating characteristic analysis showed that the blood volume value of ≥9.325 ml min(-1) 100 g(-1) predicted adrenal adenoma with sensitivity of 76.9% and specificity of 73.2%. In addition, permeability surface-area production in adenoma was higher than in non-adenoma (27.11±15.45 vs. 16.76±14.44 ml min(-1) 100 g(-1), P<0.05). The other parameters had no clear prognostic significance. CONCLUSIONS: CT perfusion imaging can quantitatively distinguish adrenal gland tumors with different histological characteristics. Especially, blood volume can be used in differentiating adrenal adenomas from nonadenomas.

Toxicological insight from AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell.

There has an effective way to prevent intimal hyperplasia on vascular smooth muscle cell (VSMC) proliferation in grafted veins. The activator protein-1 (AP-1) transcription factor plays an important role in cardiovascular generation and angioplasty. Once activated, AP-1 binds its specific DNA sequence to promote the proliferation of VSMC, differentiation, and migration. The objectives of this study were to determine toxicological effects of AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell. To suppress the expression of AP-1 gene, AP-1 siRNA was used to interfere post-transcription in rat primary VSMCs. To observe the expression of SM α-actin and downstream genes of AP-1, the activity of cell matrix metal proteinases and the migration ability of VSMC was examined by a modified Boyden chamber assay. Effects of AP-1 siRNA on proliferation and differentiation in rat VSMCs were evaluated by cell cycle analysis, DNA synthesis, MTT-test, and immunofluorescence. The results showed that the level of SM α-actin protein expression was increased. AP-1 siRNA also significantly decreased the MTT extinction value, DNA synthesis, PCNA expression, and the cell migration velocity when compared to the control group. AP-1 siRNA also clearly arrested cell cycle of VSM at the G0/G1 phase. Zymographic and Western blotting analyses showed that AP-1 siRNA suppressed serum-induced MMP-2 expression. These data suggest that the AP-1 siRNA was able to effectively inhibit the proliferation, migration, and dedifferentiation of smooth muscle cells. Thus, AP-1 siRNA provides a novel method to prevent intimal hyperplasia in blood vessel angioplasty.

Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms.

The root of Polygonum multiflorum Thunb. (PM) is utilized to treat many diseases associated with aging. Research also indicates that PM inhibits the proliferation of certain types of cancer cells. The aim of the present study was to evaluate the inhibitory effect of PM extract (PME) on the proliferation of MCF-7 cells and to investigate the underlying mechanisms. Inhibition of the proliferation of MCF-7 cells was determined by the MTT assay. Cell cycle distribution and apoptotic rates were evaluated by flow cytometry, and cell cycle and apoptosis-related protein expression was assessed by Western blotting. Apoptotic characteristics of MCF-7 cells were detected by transmission electron microscopy. The present study showed that PME at doses of 100, 150, 200 and 250 µg/ml significantly inhibited proliferation of MCF-7 cells in a time- and dose-dependent manner. Flow cytometry showed that the cell apoptotic rates were 9.1 ± 1.67 and 17.7 ± 2.93% after treatment with 100 and 200 µg/ml PME for 48 h, respectively. The proportions of cells in the G2/M phase were 37.9 ± 1.47 and 42.0 ± 1.71% after treatment with 100 and 200 µg/ml PME for 24 h, respectively. Western blot analysis showed that PME down-regulated the protein expression of Cdc25B and Cdc25C phosphatases accompanied by an increase in phospho-Cdk1, and PME promoted cytochrome c release from mitochondria into the cytosol to activate caspase-9. The present study demonstrated that PME inhibited MCF-7 cell proliferation by inducing cell cycle arrest in the G2/M phase and promoting cell apoptosis. The effects of PME on MCF-7 cells were associated with the modulation of the expression levels of proteins involved in the cell cycle and apoptosis. These data suggest that PME has promise as a treatment against breast cancer by inhibiting the proliferation of cancer cells.

Expression of VEGF and MMP-9 and MRI imaging changes in cerebral glioma.

The purpose of the present study was to investigate the association of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) expression with the histopathological grading of tumors in cerebral glioma. A total of 45 patients with pathologically confirmed cerebral glioma were divided into two groups: a low-grade group (grades I and II, 21 cases) and a high-grade group (grades III and IV, 24 cases). Immunohistochemical staining of tumor samples showed the percentages of tumors expressing VEGF and MMP-9 in the high-grade group to be 95.83 and 75%, respectively, significantly higher than those of the low-grade group (66.67 and 23.81%, P<0.05 and P<0.01, respectively). The magnetic resonance imaging (MRI) results indicated that the peripheral edema index (EI), enhancement percentage (EP), and the maximum diameter of the tumor in the high-grade group were significantly higher than those in the low-grade group (P<0.05, P<0.01, and P<0.05). Moreover, the expression of VEGF and MMP-9 was positively correlated with EI, EP and the maximum diameter of the tumor (P<0.05). Therefore, VEGF and MMP-9 expression were correlated to the invasion of glioma. The association of their expression levels with EI, EP and the maximum tumor diameter indicates that these markers may be used to estimate tumor malignancy for future clinical diagnosis and treatment.

Effects of raspberry phytochemical extract on cell proliferation, apoptosis, and serum proteomics in a rat model.

The red raspberry extract possesses potent antioxidant capacity and anticancerous activity in vitro and in vivo. The objective of this study was to determine whether red raspberry extract affected the cell cycle, angiogenesis, and apoptosis in hepatic lesion tissues from a rat model induced by diethylnitrosamine (DEN) as well as changes of serum proteomics. Rats were treated with red raspberry extract (0.75, 1.5, or 3.0 g/kg of body weight) by gavage starting 2 h after DEN administration and continued for 20 wk. Red raspberry extract inhibited cell proliferation, vascular endothelial growth factor VEGF expression, and induced apoptosis in the hepatic lesion tissues. In addition, 2 protein peaks (2597.93 and 4513.88 m/z) were identified to differentially express in the 3.0 g/kg body weight and positive control groups by serum proteomics. These results suggest that a dietary supplement with red raspberry effectively protects against chemically induced hepatic lesions in rats.

Comparison between vascular cast and three-dimensional ultrasonography on tumor vessels.

AIM: The aim of this study was to characterize the morphology of renal tumor vessels. METHODS: Twenty-two patients with kidney neoplasm underwent three-dimensional reconstruction prior to surgery. The vascular cast of kidney specimens was obtained after surgery. RESULTS: The vascular cast revealed proliferation, thickening, compression, displacement, and arteriovenous fistulae in tumor vessels, which were consistent with the findings from 3-D ultrasound (chi(2)=12.60, P<.01). CONCLUSION: Most renal cellular carcinomas are rich blood-supplied tumors with distinctive vasculature in the tumor region.

[The study of an animal model in rabbits with the early primary hyperparathyroidism].

OBJECTIVE: to study the biochemistry of blood and feature of pathology of an animal model in rabbits with the early primary hyperparathyroidism(PHPT). METHODS: 60 rabbits were divided into six groups of 10 each and fed a control diet (Ca:P, 1:0.7) or a high-phosphate diet (Ca:P, 1:7) for 1-, 2- or 3-month intervals. Compared with the control animals, serum PTH levels, serum calcium levels and serum phosphorus levels were determined. The parathyroid and kidneys of all animals were performed by the histologic examination. RESULTS: compared with the control animals, serum parathyroid hormone (PTH) levels were elevated at 1-, 2-, 3-month intervals in experimental group (t = -7.665, t = -16.033, t = 12.877 respective, P < 0.05), whereas serum calcium levels were decreased at all three time intervals (t = 6.184, t = 9.329, t = 13.842, respective, P < 0.05), but serum phosphorus levels did not change (t = 0.611, t = 1.041, t = 1.941, respective, P > 0.05). Parathyroid histopathologic studies demonstrated no change at 1 month whereas six of ten experimental animals showed mild hyperplasia at 2 months and nine of ten showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2- and 3-month in the experimental groups. CONCLUSION: the high-phosphate diet successfully induced an animal model in rabbits with the early primary hyperparathyroidism, which has a better stability and reproducibility.