Markers of Stroma in Lung Cancer: Influence of COPD.

BACKGROUND: Stroma, mainly composed by fibroblasts, extracellular matrix (ECM) and vessels, may play a role in tumorigenesis and cancer progression. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for LC. We hypothesized that markers of fibroblasts, ECM and endothelial cells may differ in tumors of LC patients with/without COPD. METHODS: Markers of cultured cancer-associated fibroblasts and normal fibroblasts [CAFs and NFs, respectively, vimentin and alpha-smooth muscle actin (SMA) markers, immunofluorescence in cultured lung fibroblasts], ECM, and endothelial cells (type I collagen and CD31 markers, respectively, immunohistochemistry) were identified in lung tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 15 LC-COPD patients and 15 LC-only patients. RESULTS: Numbers of CAFs significantly increased, while those of NFs significantly decreased in tumor samples compared to non-tumor specimens of both LC and LC-COPD patients. Endothelial cells (CD31) significantly decreased in tumor samples compared to non-tumor specimens only in LC patients. No significant differences were seen in levels of type I collagen in any samples or study groups. CONCLUSIONS: Vascular endothelial marker CD31 expression was reduced in tumors of non-COPD patients, while type I collagen levels did not differ between groups. A rise in CAFs levels was detected in lung tumors of patients irrespective of airway obstruction. Low levels of CD31 may have implications in the overall survival of LC patients, especially in those without underlying airway obstruction. Identification of CD31 role as a prognostic and therapeutic biomarker in lung tumors of patients with underlying respiratory diseases warrants attention.

Morphological estimation of incomplete uterine scar rupture (dehiscence) in post- cesarean deliveries. Immunohistochemical studies.

OBJECTIVES: No studies were found that analysed the properties of the caesarean scar, therefore the new study analysed the myometrial immunohistochemical expression of elastin, collagen type VI, alpha smooth muscle actin, smooth muscle myosin heavy chain, and endothelial cell marker CD31. The aim of the study was to determine the risk of uterine rupture in future pregnancies. MATERIAL AND METHODS: A total of 89 women of Caucasian ethnicity were eligible: 20 healthy pregnant women, who underwent repeat caesarean section complicated by incomplete uterine scar rupture before labour, and 69 healthy pregnant women, who underwent repeat caesarean section without subsequent uterine scar rupture as the control group. In all cases, uterine tissue sample from the scarred region was collected during the caesarean section operation. RESULTS: The lack of observed significant changes of elastin, collagen type VI, alpha smooth muscle actin, smooth muscle myosin heavy chain and endothelial cell marker CD31 concentrations in ruptured and unruptured uteri indicates that these components cannot be found to be a marker of risk of uterine rupture in future pregnancies. CONCLUSIONS: It could be suggested that the examined components do not contribute to the mechanism of maintaining integrity and are not responsible for the biomechanical properties of the uterine scar.

Effects of Buyang Huanwu Decoction on Endothelial-mesenchymal Transformation of Lung Tissue in Idiopathic Pulmonary Fibrosis Model Rats and Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation （EndMT） of lung tissue in idiopathic pulmonary fibrosis （IPF） model rats， and to explore its potential mechanism. METHODS： Male SD rats were randomly divided into normal group， model gorup， dexamethasone group [0.405 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6.435， 12.87， 25.74 g/（kg·d）， by raw material]， with 8 rats in each group. Except for normal group， other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling， normal group and model group were given water intrgastrically [10 mL/（kg·d）]； administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 days. 24 h after last medication， the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1， vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin， fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS： Compared with normal group， the expression of endothelial cell markers were decreased significantly in lung tissue of model group， while the expressipon of interstitial cell markers， Notch4 and DLL4 were increased significantly （P＜0.01）. Compared with model group， the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups， while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group； the expression of interstitial cell markers， Notch4 and DLL4 were decreased significantly， while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group （P＜0.05 or P＜0.01）. CONCLUSIONS： Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT， the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.

HBME-1 expression in differentiated thyroid carcinoma and its correlation with the ultrasonic manifestation of thyroid.

We investigated expression of the protein human bone marrow endothelial cell marker-1 (HBME-1) in differentiated thyroid carcinoma tissues, and analyzed its correlation with ultrasonic manifestation of thyroid. The immunohistochemistry (IHC) staining method was used to measure the expression of HBME-1 in patient with nodular goiter (control group), papillary differentiated thyroid carcinoma (papillary carcinoma group) and follicular differentiated thyroid carcinoma (follicular carcinoma group) to investigate the differences in expression of HBME-1. We further analyzed the correlation of the expression of HBME-1 in the papillary carcinoma group and the follicular carcinoma group with ultrasonic manifestation of thyroid. In both the papillary carcinoma group and the follicular carcinoma group, the levels of HBME-1 in affected tissues and the IHS score of HBME-1 expression were higher than those in the control group (p<0.05). In the papillary carcinoma group, the mean IHS score of HBME-1 expression in affected tissues was higher than in the follicular carcinoma group (p<0.05). There were no statistically significant differences in comparison to HBME-1 expression in affected tissues between the papillary carcinoma group and the follicular carcinoma group (p>0.05). Between the papillary carcinoma group and the follicular carcinoma group, the differences in the comparison of the nodule diameter, echo, shape, boundary, calcification and blood flow signal were statistically significant (p<0.05), but incidence rate of enlargement of cervical lymph nodules between the groups were not statistically significant (p>0.05). Among patients in the papillary carcinoma group, the comparison of the nodule diameter, echo, shape, boundary, calcification and blood flow signal between the HBME-1-positive patients and the HBME-1-negative patients showed no statistical significance (p>0.05), but in the nodules of HBME-1-positive patients, the proportion of blood flow signal was higher than that in the nodules of HBME-1-negative patients. Among patients in the follicular carcinoma group, there was no statistically significant differences in the comparison of ultrasonic manifestation of thyroid (p>0.05). Therefore, there are difference in HBME-1 expression and ultrasonic manifestations of thyroid in patients with papillary carcinoma and follicular differentiated thyroid carcinoma.

Desmin expression profile in reactive astrocytes in the 3-nitropropionic acid-lesioned striatum of rat: Characterization and comparison with glial fibrillary acidic protein and nestin.

Desmin, a muscle-specific, type-III intermediate-filament protein, is reportedly expressed in astrocytes in the central nervous system. These cells become reactive astrocytes in response to brain injuries. To elucidate whether desmin is involved in this process, we examined the spatiotemporal expression profiles of desmin and their relationship with two astroglial intermediate filaments, glial fibrillary acidic protein (GFAP) and nestin, in the striatum of rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). Weak, constitutive immunoreactivity for desmin was observed in astrocytes generally, and in reactive astrocytes in the peri-lesional area, its expression increased in parallel with that of GFAP over 3 d post-lesion and was maintained until at least day 28. Desmin, GFAP, and nestin showed characteristic time-dependent expression patterns in reactive astrocytes forming the astroglial scar; delayed and long-lasting induction of desmin and GFAP, and rapid but transient induction of nestin. In the lesion core, desmin was expressed in two categories of perivascular cells: nestin-negative and nestin-positive. These findings show that desmin, together with GFAP and nestin, is a dynamic component of intermediate filaments in activated astroglia, which may account for the dynamic structural changes seen in these cells in response to brain injuries.

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity.

BACKGROUND: This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. METHODS: The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm(3), daily EMF treatments were started by placing the cage of mice within the EMF field. Treatment ranged from 10 to 20 milli-Tesla (mT) and was given for 3 to 80 minutes either once or twice a day for 12 days. Tumors were measured and volumes calculated each 3-4 days. RESULTS: Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective tumor growth suppressor. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization. CONCLUSION: It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy.

Suprabasin as a novel tumor endothelial cell marker.

Recent studies have reported that stromal cells contribute to tumor progression. We previously demonstrated that tumor endothelial cells (TEC) characteristics were different from those of normal endothelial cells (NEC). Furthermore, we performed gene profile analysis in TEC and NEC, revealing that suprabasin (SBSN) was upregulated in TEC compared with NEC. However, its role in TEC is still unknown. Here we showed that SBSN expression was higher in isolated human and mouse TEC than in NEC. SBSN knockdown inhibited the migration and tube formation ability of TEC. We also showed that the AKT pathway was a downstream factor of SBSN. These findings suggest that SBSN is involved in the angiogenic potential of TEC and may be a novel TEC marker.

Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.

Targeting tumor angiogenesis is an established strategy for cancer therapy. Because angiogenesis is not limited to pathological conditions such as cancer, molecular markers that can distinguish between physiological and pathological angiogenesis are required to develop more effective and safer approaches for cancer treatment. To identify such molecules, we determined the gene expression profiles of murine tumor endothelial cells (mTEC) and murine normal endothelial cells using DNA microarray analysis followed by quantitative reverse transcription-polymerase chain reaction analysis. We identified 131 genes that were differentially upregulated in mTEC. Functional analysis using siRNA-mediated gene silencing revealed five novel tumor endothelial cell markers that were involved in the proliferation or migration of mTEC. The expression of DEF6 and TMEM176B was upregulated in tumor vessels of human renal cell carcinoma specimens, suggesting that they are potential targets for antiangiogenic intervention for renal cell carcinoma. Comparative gene expression analysis revealed molecular differences between tumor endothelial cells and normal endothelial cells and identified novel tumor endothelial cell markers that may be exploited to target tumor angiogenesis for cancer treatment.

Tissue-specific venous expression of the EPH family receptor EphB1 in the skin vasculature.

BACKGROUND: The major arteries and veins are formed early during development. The molecular tools to identify arterial and venous endothelial cells improve our understanding of arterial-venous differentiation and branching morphogenesis. Compared with arterial differentiation, relatively little is known about what controls venous development, due to lack of definitive molecular markers for venous endothelial cells. RESULTS: Here we report that the antibody against EphB1, an EphB class receptor, makes it possible to establish a reliable whole-mount immunohistochemical analysis of venous identity with greater resolution than previously possible in embryonic and adult skin vasculature models. EphB1 expression is restricted to the entire venous vasculature throughout embryonic development to adulthood, whereas the previously established venous marker EphB4 is also detectable in lymphatic vasculature. This venous-restricted expression of EphB1 is established after the vascular remodeling of the primary capillary plexus has occurred. Compared with its venous-specific expression in the skin, however, EphB1 is not restricted to the venous vasculature in yolk sac, trunk and lung. CONCLUSIONS: These studies introduce EphB1 as a new venous-restricted marker in a tissue-specific and time-dependent manner.