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MVD
Kinds of MVD Selected AbstractsDifferences and relationships of thymidine phosphorylase expression in tumor-associated macrophages and cancer cells in squamous cell carcinoma of the esophagusDISEASES OF THE ESOPHAGUS, Issue 1 2002N. Koide SUMMARY. Thymidine phosphorylase (TP), which has been shown to be identical to platelet-derived endothelial cell growth factor, is expressed in tumor-associated macrophages (TAMs) as well as cancer cells. The aim of this study was to clarify the differences or relationships of TP expression in TAMs and cancer cells in esophageal squamous cell carcinoma (SCC). Tissues samples were taken from 56 patients with esophageal SCC after curative surgery. The expression of TP in TAMs or SCC cells was examined using a monoclonal antibody to TP (clone 654,1). Microvessels in SCC that stained positively for Factor VIII-related antigen were counted (microvessel density, MVD). Macrophages in SCC that stained positively for CD68 antigen were counted (monocytic count). Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated. The expression of TP in stromal cells and cancer cells was observed in 43 (76.8%) and 33 patients (58.9%), respectively. There were significant correlations between TP expression in stromal cells (TAMs) as well as in cancer cells and venous invasion, distant metastasis, or MVD. There was a correlation between TP expression in cancer cells and lymph node metastasis, and there were correlations between TP expression in TAMs and monocytic count or Ki-67 LI; however, there was no correlation between TP expression in TAMs and lymph node metastasis. On the other hand, in SCCs with TP expression in both TAMs and cancer cells, higher frequencies of venous invasion and distant metastasis, higher MVD and lower apoptotic index were observed than in other SCCs. The 5-year survival rate in patients with TP expression in both TAMs and cancer cells was poorer than that in patients with TP expression in neither TAMs and cancer cell. In conclusion, these results suggest that co-expression of TP in TAMs and cancer cells is strongly associated with angiogenic promotion and distant metastasis. However, other effects of TP, such as promotion of tumor growth and lymph node metastasis, may be different depending on whether these are expressed in TAMs or cancer cells in esophageal SCCs. Patients with coexpression of TP in TAMs and cancer cells may be associated with a poor prognosis. [source] Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma,a prospective study,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2003Brigette B. Y. Ma FRACP Abstract Background. This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC). Methods. Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage. Results. On univariate analysis, EGFR expression correlated with poorer OS (p = .0001), DFS (p = .01), shorter TTP (p = .0001), and advanced T stage (p = .036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p = .04) and shorter TTP in a subgroup of patients with UICC stage III,IV disease. HER2 expression was associated with advanced UICC stage (p = .006). The presence of p53 expression correlated with poorer DFS (p = .01) and a trend toward shorter TTP (p = .06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP. Conclusions. EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 864,872, 2003 [source] The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma,HEMATOLOGICAL ONCOLOGY, Issue 4 2004E. Hatjiharissi Abstract The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-,), which have angiogenic potential and interleukin-6 (IL-6), IL-1,, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-,) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-,, TGF-,, IL-1, did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology. Copyright © 2005 John Wiley & Sons, Ltd. [source] Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinomaHISTOPATHOLOGY, Issue 4 2010Satoshi Fujii Fujii S, Yamazaki M, Muto M & Ochiai A (2010) Histopathology56, 510,522 Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinoma Aims:, Superficial squamous epithelial lesions of the pharynx are increasingly recognized by architectural changes in the intraepithelial papillary capillary loop (IPCL) assessed by narrow-band imaging (NBI). The aim was to explore the histology of squamous epithelial precursor lesions and superficial-type pharyngeal squamous cell carcinoma (STPSCC), including squamous cell carcinoma (SCC) in situ and early invasive SCC, by focusing on microvascular irregularities to investigate the composition of those lesions and to explore the pathological characteristics of STPSCCs. Methods and results:, Several pathological factors including thickness of intraepithelial squamous cell carcinoma (IESCC) and tumour thickness and microvascular density (MVD) were examined in 104 STPSCCs from 69 patients. The results show that architectural change of IPCL was recognized in precursor lesions in parallel with architectural disturbance and cytological atypia for criteria of diagnosing dysplasia. In 104 STPSCCs, the MVD of IESCC was correlated with the thickness of IESCC (P = 0.0115). Moreover, invasive SCC showed significantly higher MVD of IESCC (P = 0.0078) and there was significant correlation between the thickness of IESCC and subepithelial invasion (P < 0.0001). Conclusions:, Microvascular irregularities are an important pathological factor in carcinogenesis and early invasiveness of SCC of the pharynx. [source] Prognostic significance of HIF-1, polymorphisms in transitional cell carcinoma of the bladderINTERNATIONAL JOURNAL OF CANCER, Issue 6 2008Junichi Nadaoka Abstract Recently, two single nucleotide polymorphisms in the hypoxia-inducible factor-1, (HIF-1,) gene, P582S and A588T, were shown to cause significantly higher transcriptional activity than the wild type. We investigated the association between the HIF-1, polymorphisms and the incidence and progression of transitional cell carcinoma of the bladder, and the relationship between the polymorphisms and the tissue vascular endothelial growth factor (VEGF) level or microvessel density (MVD). A total of 219 patients with bladder cancer and 464 healthy native Japanese control subjects were enrolled. Tissue VEGF and HIF-1, expression levels and the mean MVD were evaluated in 73 radical cystectomy specimens by immunohistochemistry. The HIF-1, genotype did not significantly influence the incidence or disease status of bladder cancer. Among patients who underwent radical cystectomy, those with a variant allele had significantly worse disease-free survival (p = 0.001) and disease-specific survival (p = 0.006) than those without a variant allele. Multivariate analysis using a Cox proportional hazard model revealed that the presence of a variant allele was an independent predictor of disease-free survival (HR = 3.10, 95%CI = 1.38,6.99, p = 0.006). Although not statistically significant, the moderate/high expression levels of VEGF in tumor tissues were more frequently observed in patients with a HIF-1, variant allele (11/13, 84.6%) than in those without (33/60, 55%, p = 0.063). The HIF-1, polymorphisms may have a significant influence on the poor prognosis of the patients undergoing radical cystectomy for bladder cancer, while they seem to have no relation to the bladder cancer occurrence. © 2007 Wiley-Liss, Inc. [source] Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL miceINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Kaeko Hirai Abstract Heme oxygenase (HO)-1 is a key player reducing cytotoxicity and enhancing protumoral effects of nitric oxide (NO). We examined zinc protoporphyrin (ZnPP) IX, an HO-1 inhibitor, to affect tumor growth of LL/2 mouse lung cancer cells. ZnPPIX reduced HO-1 expression and HO activity in LL/2 cells, whereas cobalt PPIX (CoPPIX), an HO-1 activator, increased both. LL/2 cells treated with sodium nitropurusside, an NO donor, showed growth inhibition dose-dependently, which was enhanced by ZnPPIX cotreatment, but was reduced by CoPPIX. In mice tumors, ZnPPIX decreased HO-1 expression. LL/2-tumors were found in 88% (7/8) vehicle-treated mice, whereas tumors were found in 38% (3/8) and 25% (2/8) mice treated with 5 and 20 ,g/mouse ZnPPIX, respectively (p = 0.0302). Tumor growth was inhibited dose-dependently by ZnPPIX. Vascular endothealial growth factor concentration in tumors was reduced by ZnPPIX (p = 0.0341). Microvessel density (MVD) in ZnPPIX-treated tumors was lower than that in vehicle-treated tumors (p = 0.0362). Apoptotic cell count in ZnPPIX-treated tumors was higher than that in vehicle-treated tumors (p = 0.0003). In contrast, CoPPIX treatment increased HO-1 expression, enhanced tumorigenicity and MVD and reduced apoptosis. From these findings, inhibition of HO-1 by ZnPPIX provides relevant antitumoral effects. © 2006 Wiley-Liss, Inc. [source] Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stromaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Takafumi Sangai Abstract Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1,/, ,-gal Tg or RAG-1,/, GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. © 2005 Wiley-Liss, Inc. [source] Stromelysin-3 expression is an early event in human oral tumorigenesisINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Shilpi Soni Abstract Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis. © 2003 Wiley-Liss, Inc. [source] Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseasesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007Ala'eddin Jebreel Summary Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0,3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology. [source] Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004TETSUYA IMAO Abstract Background: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival. Methods: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34. Results: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 ± 67 and 58 ± 35 per ×400 field (mean ± SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 ± 22 and 142 ± 54 per ×400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors. Conclusion: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor. [source] VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous modelJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2009R. Patruno Abstract Canine cutaneous mast cell tumour (CMCT) is a common cutaneous tumour in dog, with a higher incidence than in human. CMCT is classified in three subgroups, well and intermediately differentiated (G1 and G2), corresponding to a benign disease, and poorly differentiated (G3), corresponding to a malignant disease, which metastasize to lymph nodes, liver, spleen and bone marrow. In this study, we have evaluated serum (S), platelet-poor plasma (P-PP), plasma-activated platelet rich (P-APR) and cytosol vascular endothelial growth factor (VEGF) concentrations, microvascular density (MVD) and mast cell density (MCD) in a series of 86 CMCTs and we have correlated these parameters with each other, by means of ELISA detection of VEGF and immunohistochemistry. Results show that VEGF level from cytosol P-APR and MVD were significantly higher in G3 CMCTs as compared to G1 or G2 subgroups. Moreover, a significantly strong correlation among VEGF levels from P-PAR and cytosol, MVD and MCD was found in G3 subgroup. Because VEGF levels from P-APR well correlated with MVD and malignancy grade in CMCT, we suggest that VEGF might be secreted from MCs and it may be a suitable surrogate inter-species angiogenetic markers of tumour progression in CMCT. Finally, CMCT seems to be a useful model to study the role of MCs in tumour angiogenesis and inhibition of MCs degranulation or activation might be a new anti-angiogenic strategy worthy to further investigations. [source] Coronary Artery Bypass Surgery Versus Percutaneous Coronary Intervention with Drug-Eluting Stent Implantation in Patients with Multivessel Coronary DiseaseJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2007ZHEN KUN YANG M.D. Background: Drug-eluting stents (DES) constitute a major breakthrough in restenosis prevention after percutaneous coronary intervention (PCI). This study compared the clinical outcomes of PCI using DES versus coronary artery bypass graft (CABG) in patients with multivessel coronary artery disease (MVD) in real-world. Methods: From January 2003 to December 2004, 466 consecutive patients with MVD underwent revascularization, 235 by PCI with DES and 231 by CABG. The study end-point was the incidence of major adverse cardiovascular events (MACEs) at the first 30 days after procedure and during follow-up. Results: Most preoperative characteristics were similar in the two groups, but left main disease (24.7% vs 2.6%, P<0.001) and three-vessel disease (65% vs 54%, P = 0.02) were more prevalent in CABG group. The number of coronary lesions was also greater in CABG group (3.7 ± 1.1 vs 3.3 ± 1.1, P<0.001). Despite higher early morbidity (3.9% vs 0.8%, P = 0.03) associated with CABG, there were no significant differences in composite MACEs at the first 30 days between the two groups. During follow-up (mean 25±8 months), the incidence of death, myocardial infarction, or cerebrovascular event was similar in both groups (PCI 6.3% vs CABG 5.6%, P = 0.84). However, bypass surgery still afforded a lower need for repeat revascularization (2.8% vs 10.4%, p = 0.001). Consequently, overall MACE rate (14.5% vs 7.9%, P = 0.03) remained higher after PCI. Conclusion: PCI with DES is a safe and feasible alternative to CABG for selected patients with MVD. The reintervention gap was further narrowed in the era of DES. Aside from restenosis, progression of disease needs to receive substantial emphasis. [source] Dynamic Gd-DTPA enhanced MRI as a surrogate marker of angiogenesis in tissue-engineered bladder constructs: A feasibility study in rabbitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005Hai-Ling Margaret Cheng PhD Abstract Purpose To evaluate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess angiogenesis in tissue-engineered bladder constructs in a blinded animal study, and compare different analysis approaches and their correlation with microvessel density (MVD). Materials and Methods Constructs fortified with vascular endothelial growth factor (VEGF) for enhanced vascularity were grafted onto the bladder in nine rabbits. DCE-MRI of Gd-DTPA uptake was performed and analyzed using Tofts' model, the area under the concentration time curve (AUC), and the uptake slope. DCE-MRI parameters were compared to MVD determined with CD31 immunohistochemistry. Results Significantly increased MVD was found in the high VEGF group (20 ng/g of tissue) but not at low VEGF (10 ng/g) (2.3× increase, P = 0.035 vs. 1.1× over control). Enhanced permeability at low VEGF was suggested by elevated Ktrans, but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC8min (r = 0.705, P = 0.034). Furthermore, AUC8min provided the most precise discrimination between different VEGF preparations and was the only parameter to show a significant increase (P = 0.0058) consistent with MVD changes at high VEGF. Conclusion Findings support DCE-MRI for evaluating angiogenesis in bladder constructs and suggest vessel changes other than density. Future studies should incorporate larger contrast agents and permeability assessment to devise an optimal DCE-MRI strategy. J. Magn. Reson. Imaging 2005;21:415,423. © 2005 Wiley-Liss, Inc. [source] Angiogenic and lymphangiogenic microvessel density in recurrent pleomorphic adenomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2009Andresa B. Soares Background:, Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to determine if there is a difference between RPA and the pleomorphic adenoma (PA) without recurrence related to tumor blood and lymphatic vascularization. Moreover, we compared the microvessel density (MVD) between cell-rich areas (predominance of epithelial cells) and cell-poor areas (predominance of myxoid and chondroid areas) of the stroma of PA and RPA. In addition, immunohistochemical staining for the Ki-67 antigen was conducted simultaneously to evaluate cell proliferation in PA and RPA. Methods:, A total of 19 cases of PA and 24 cases of RPA, blood, and lymphatic vessels were analyzed by immunohistochemical technique using the antibodies CD34, CD105, D2-40, and Ki-67. Results:, Comparing no recurrent with recurrent tumor, no significant difference was found in terms of lymphatic vessel density, MVD, and proliferation index. When MVD and proliferation index were compared with different areas in cellular composition (cell-rich and cell-poor areas), there was a significant difference in PA, as well as in RPA. Conclusion:, This study shows that although RPA presents more aggressive clinical behavior than PA, there is no difference between tumor blood and lymphatic vascularization, suggesting that there is no correlation between vascularity and risk of recurrence. Furthermore, vascularized stroma in PA, as well as RPA, depends on the proportion of the cellular composition. [source] Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancerJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003Roland Sedivy Abstract Background:, The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease. Methods:, Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients. Results:, LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease. Conclusions:, VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases. [source] Synthesis and biological activity of homoarginine-containing opioid peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 1 2007Jan Izdebski Abstract Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{,,,,-[Z(2Br)]2}-OH and Boc-Har{,,,,-[Z(2Cl)]2}-OH, were prepared by guanidinylation of Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)-OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide-resin was guanidinylated with N,N,-[Z(2Br)]2 - or N,N,-[Z(2Cl)]2 - S -methylisourea. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin-like enzymes. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008Ken Sasaki MD Abstract Background and Objectives The chemokine CXCL12 and its receptor CXCR4 are involved in cell migration, proliferation, and angiogenesis, and promote organ-specific localization of distant metastases in various carcinomas. We examined their expression and microvessel density (MVD) in submucosal esophageal squamous cell carcinoma (ESCC) and analyzed their connection to clinicopathological findings including lymph node micrometastasis (LMM). Methods Eighty-six patients with submucosal ESCC underwent curative resection from 1985 to 2002. Immunohistochemical staining of CXCL12, CXCR4, and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. MVD was calculated from CD34 expression, and LMM detected by cytokeratin staining. Results Expression of CXCL12, but not CXCR4, correlated with lymph node metastasis. There was no significant correlation between the expression of CXCL12 and/or CXCR4 and MVD. LMM was detected in 8 cases and 14 lymph nodes. CXCL12 expression and high MVD were found in tumors with lymph node metastasis including LMM. Furthermore, in the CXCR4-positive tumors, positive CXCL12 expression was more significantly correlated with lymph node metastasis and/or LMM than negative CXCL12 expression. Conclusions Evaluation of CXCL12 and CXCR4 expression should assist detection of lymph node metastasis including LMM in submucosal ESCC. J. Surg. Oncol. 2008;97:433,438. © 2008 Wiley-Liss, Inc. [source] IV-DSA is a new diagnostic tool for axillary lymph node metastasis in breast cancer patientsJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2004Osamu Watanabe MD Abstract Background and Objective The aim of this study is to know whether intravenous digital subtraction angiography (IV-DSA) is useful to detect axillary lymph node metastasis of breast cancer and to evaluate the anigiogenesis of lymph nodes in the axilla. Patients and Methods Forty three primary breast cancer patients (N0: 26 cases, N1: 5 cases, N2: 2 cases) who underwent IV-DSA between January and November 2000 were included in the study. Infinix CB apparatus (Toshiba, Japan) was used to collect IV-DSA images and when a mass became stained in the axilla, it was considered to be metastatic. The angiogenesis was studied by examining microvessel density (MVD) after lymph node immunostaining for factor VIII. Primary tumor was detected by IV-DSA in all 43 cases. Results Axillary lymph node metastases were detected by IV-DSA in 34.9% of cases (15/43), and by pathology in 37.2% (16/43). The sensitivity, specificity, and accuracy of the diagnostic method were 75.0% (12/16), 88.9% (24/27), and 83.7% (36/43), respectively. MVD, calculated after immunostaining for factor VIII, was significantly lower in the in metastatic region of lymph nodes identified by DSA (88.5,±,35.0) than in metastasis-free lymph nodes (141.1,±,34.0, P,<,0.0001). Conclusions IV-DSA is useful in the diagnosis of axillary lymph node metastasis of breast cancer. Our results suggest that the primary factors involved in the mechanism of DSA display may be different from high/low MVC values. J. Surg. Oncol. 2004;87:75,79. © 2004 Wiley-Liss, Inc. [source] Serum Cardiac Troponin I Concentration in Dogs with Precapillary and Postcapillary Pulmonary HypertensionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010C. Guglielmini Background: Pulmonary hypertension (PH) is a disease condition leading to right-sided cardiac hypertrophy and, eventually, right-sided heart failure. Cardiac troponin I (cTnI) is a circulating biomarker of cardiac damage. Hypothesis: Myocardial damage can occur in dogs with precapillary and postcapillary PH. Animals: One hundred and thirty-three dogs were examined: 26 healthy controls, 42 dogs with mitral valve disease (MVD) without PH, 48 dogs with pulmonary hypertension associated with mitral valve disease (PH-MVD), and 17 dogs with precapillary PH. Methods: Prospective, observational study. Serum cTnI concentration was measured with a commercially available immunoassay and results were compared between groups. Results: Median cTnI was 0.10 ng/mL (range 0.10,0.17 ng/mL) in healthy dogs. Compared with the healthy population, median serum cTnI concentration was increased in dogs with precapillary PH (0.25 ng/mL; range 0.10,1.9 ng/mL; P < .001) and in dogs with PH-MVD (0.21 ng/mL; range 0.10,2.10 ng/mL; P < .001). Median serum cTnI concentration of dogs with MVD (0.12 ng/mL; range 0.10,1.00 ng/mL) was not significantly different compared with control group and dogs with PH-MVD. In dogs with MVD and PH-MVD, only the subgroup with decompensated PH-MVD had significantly higher cTnI concentration compared with dogs with compensated MVD and PH-MVD. Serum cTnI concentration showed significant modest positive correlations with the calculated pulmonary artery systolic pressure in dogs with PH and some echocardiographic indices in dogs with MVD and PH-MVD. Conclusions and Clinical Importance: Serum cTnI is high in dogs with either precapillary and postcapillary PH. Myocardial damage in dogs with postcapillary PH is likely the consequence of increased severity of MVD. [source] Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2002Clarence Kvart We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25,0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (±30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P= .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 ± 50 days for dogs in the treatment group and 1,130 ± 50 days for dogs in the placebo group (P= .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P= .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P= .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study. [source] Single nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer riskMOLECULAR CARCINOGENESIS, Issue 9 2010Gudrun Knechtel Abstract With an incidence of about 300,000 new cases colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe and the United States. Environmental and genetic factors influence CRC risk. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1 alpha and HIF-1 beta, plays a critical role in oxygen homeostasis and is involved in angiogenesis and cell proliferation. The gene for the HIF-1 alpha subunit (HIF1A) carries two common missense mutations,P582S (rs11549465) and A588T (rs11549467),which both have been related to increased trans-activation capacity of HIF1A. In our case,control study we investigated the association between these polymorphisms and CRC risk. We investigated 381 patients with histologically confirmed CRC and 2156 control subjects. HIF1A genotypes were determined by exonuclease (TaqMan) assays. For determination of microvessel density (MVD) tumor sections were stained using a mouse monoclonal antibody recognizing the pan-endothelial marker CD31. In a multivariate logistic regression analysis including age and sex neither the HIF1A 582S allele (Odds ratio: 1.204; 95% confidence interval 0.911,1.592; P,=,0.193) nor the 588T allele was significantly associated with CRC (Odds ratio: 0.851; 95% confidence interval 0.444,1.631; P,=,0.626). However, in an exploratory analysis, the HIF1A 588T allele was associated with tumor localization (P,=,0.016) and tumor size (P,=,0.003). MVD was similar in tumors of patients carrying HIF1A 588T allele and patients without this rare allele. We conclude that functional polymorphisms in the HIF1A gene do not modify CRC risk but maybe associated with clinic-pathological features of the disease. © 2010 Wiley-Liss, Inc. [source] Coexpression of heparanase, basic fibroblast growth factor and vascular endothelial growth factor in human esophageal carcinomasPATHOLOGY INTERNATIONAL, Issue 8 2004Shuji Mikami Heparan sulfate (HS), which is degraded by heparanase, plays an important role in cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir for various growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). In the present study, we examined the immunohistochemical expression of heparanase, bFGF and VEGF, and evaluated the correlation between their expression and microvessel density (MVD) in human esophageal carcinomas. Heparanase, bFGF and VEGF were immunolocalized predominantly to the carcinoma cells, but they were also localized to the endothelial cells of microvessels near the carcinoma cell nests. In carcinomas with invasion of the muscular layer or adventitia, heparanase staining was stronger at the invasive areas of carcinomas than the intraepithelial spread. Expression of heparanase and bFGF and the degree of MVD were associated, with, tumor, invasion,, lymph, node, metastasis, and pathological stages. Cases with positive staining for heparanase, bFGF or VEGF tended to have a higher MVD than those without staining, and carcinomas with concomitant expression of heparanase, bFGF and VEGF showed the highest MVD. The level of heparanase mRNA expression was directly correlated with the MVD. In addition, heparanase-positive cases had a higher positive ratio of bFGF and VEGF compared with the heparanase-negative cases. These data suggest the possibility that heparanase may contribute to not only cancer cell invasion but also angiogenesis probably through degradation of HS in the ECM and release of bFGF and VEGF from the HS-containing ECM. [source] Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinomaPATHOLOGY INTERNATIONAL, Issue 10 2003Hua-Chuan Zheng To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry. Microvessel density (MVD) was counted using the anti-CD34 antibody. The expressions of PTEN and MMP-7, and MVD were compared with the clinicopathological parameters of tumors, and the relationship between PTEN and MMP-7 expression and MVD was analyzed. It was found that PTEN was expressed less frequently in primary gastric carcinoma cells than in adjacent epithelial cells (P < 0.05), whereas this was reversed for MMP-7 (P < 0.05). PTEN expression was negatively correlated with invasion, metastasis, growth pattern, Lauren's classification and histological classification (P < 0.05). Matrix metalloproteinase-7 expression was positively associated with tumor size, Borrmann's classification, invasive depth, metastasis and TNM staging (P < 0.05), but negative with PTEN expression (P < 0.05). A positive correlation of MVD with tumor size, invasive depth, metastasis and TNM staging was found (P < 0.05). Microvessel density depended on decreased PTEN expression and increased MMP-7 expression (P < 0.05). The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. Close correlation between PTEN on MMP-7 expression provided a novel insight into the regulatory effects of PTEN on MMP-7 expression in gastric carcinoma. [source] Prognostic value of bone marrow angiogenesis in multiple myeloma: Use of light microscopy as well as computerized image analyzer in the assessment of microvessel density and total vascular area in multiple myeloma and its correlation with various clinical, histological, and laboratory parametersAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2006Sahibinder Singh Bhatti Abstract We studied the prognostic value of parameters of angiogenesis on bone marrow biopsies in newly diagnosed multiple myeloma (MM) patients. Angiogenesis parameters studied were the microvessel count done manually on light microscopy (MVD-A), microvessel count done by using computerized image analyzer (MVD-B), and total vascular area (TVA) measured by computerized image analyzer. One hundred ten newly diagnosed cases of MM treated at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and responses to the treatment on follow-up. Twenty age- and sex-matched controls were studied for comparing with angiogenesis of the test cases. Bone marrow microvessels were examined using immunohistochemical staining for CD34. MVD-A (range 4.9,85.2; mean 28.2; SD 19.4), MVD-B (range 2.0,26.9; mean 11.7; SD 5.9), and TVA measured in percentage (range 0.1,17.1; mean 2.4; SD 2.5) were measured for test cases (n = 110). Grading of angiogenesis parameters of the test cases were done; such that angiogenesis parameters of controls (taken as baseline) were grade I. There was a statistically highly significant correlation between (MVD-A vs MVD-B, pcc = 0.92; MVD-A vs TVA, pcc = 0.78; MVD-B vs TVA, pcc = 0.76). The myeloma cases had significantly higher angiogenesis parameters when compared with controls (Kruskall-Wallis test, P < 0.001). "Complete responders" (n = 38/110) had significant lower angiogenesis (Mann-Whitney U test, P < 0.001) than "nonresponders" (n = 72/110). On treatment follow-up "rapid disease progressors" had the highest levels of angiogenesis (mean rank for MVD-A = 84.7, MVD-B = 82.1, and TVA = 81.1). On multivariate (logistic regression) analysis, factors found to have independent prognostic significance in complete responders (adjusted odd ratio (95% CI, P value)] were: (a) MVD-B grade I [0.134 (0.10,0.16, P < 0.001)], (b) clinical substage A [0.163 (0.12,0.19, P = 0.008)], (c) Bartl's histological stage II & I [0.262 (0.2,0.32, P = 0.021)], (d) MVD-A grade I [0.28 (0.22,0.36, P = 0.03)], (e) ,2 microglobulin levels less than 3,400 ng/dl [0.31 (0.23,0.42, P = 0.04)]. Kaplan-Meier survival analysis for myeloma-related death (n = 16) shows a mean survival time (in months) of 24.75; SE = 3; 95% CI = 21,28. We conclude that MVD (particularly MVD-B) is a very good predictor for the complete response in patients of MM and should be done routinely on bone marrow biopsies. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Differential protein expression between normal, early-stage, and late-stage myxomatous mitral valves from dogsPROTEOMICS - CLINICAL APPLICATIONS, Issue 12 2009Carla M. R. Lacerda Abstract Valvular heart disease accounts for over 20,000 deaths and 90,000 hospitalizations yearly in the United States. Myxomatous valve disease (MVD) is the most common disease of the mitral valve in humans and dogs. MVD is pathologically identical in these species and its pathogenesis is poorly understood. The objectives of this study were to (i) develop proteomic methodology suitable for analysis of extracellular matrix-rich heart valve tissues and (ii) survey over- and under-expressed proteins that could provide mechanistic clues into the pathogenesis of MVD. Normal, early-stage, and late-stage myxomatous mitral valves from dogs were studied. A shotgun proteomic analysis was used to quantify differential protein expression. Proteins were classified by function and clustered according to differential expression patterns. More than 300 proteins, with 117 of those being differentially expressed, were identified. Hierarchical sample clustering of differential protein profiles showed that early- and late-stage valves were closely related. This finding suggests that proteome changes occur in early degeneration stages and these persist in late stages, characterizing a diseased proteome that is distinct from normal. Shotgun proteome analysis of matrix-rich canine heart valves is feasible, and should be applicable to human heart valves. This study provides a basis for future investigations into the pathogenesis of MVD. [source] Microvessel Density in Head and Neck Squamous Cell Carcinoma Primary Tumors and Its Correlation with Clinical Staging ParametersTHE LARYNGOSCOPE, Issue 3 2006Eric J. Lentsch MD Abstract Objective: Our objective was to assess angiogenesis in head and neck squamous cell primary tumors and measure its correlation with tumor site and clinical and pathologic staging parameters. Study Design: Patients from the tumor registries of the University of Louisville and affiliated hospitals who had biopsy-proven head and neck squamous cell carcinoma were retrospectively assessed over a 5-year period (1995,2000). Methods: Patient records were reviewed for tumor site, TNM staging, surgical treatment, and tumor pathologic staging data. Cell blocks were obtained for each of the study patients, and CD31 staining was used to measure microvessel density (MVD) in areas of primary tumor hot spots. Results: Twenty-eight consecutive patients met inclusion criteria and had adequate cell blocks for evaluation. MVD for T3 staged (41.2 MVD, mean) and T4 staged (36.4 MVD, mean) tumors were higher than earlier staged T1 staged (31.3 MVD, mean) and T2 staged (24.9 MVD, mean) tumors. Laryngeal T3 and T4 tumors had MVDs as high as 43.4 MVD (mean) and 40.4 MVD (mean), respectively, compared with a 23.9 MVD for T2 tumors. This difference was statistically significant (P < .01). Our report indicates a trend toward increasing MVD with N-stage. Conclusion: Our series demonstrates that there is a strong correlation between MVD in primary tumor hot spots and tumor T-stage, which implies that tumor angiogenesis may be a factor in tumor progression. [source] Quantification of Angiogenesis in Otosclerosis,THE LARYNGOSCOPE, Issue 5 2005Robert W. Jyung MD Abstract Objectives/Hypothesis: The determinants of clinical versus histologic otosclerosis are unknown, but angiogenesis is associated with active disease. We hypothesized that quantification of angiogenesis in otosclerotic human temporal bones could reveal significant differences between clinical and histologic cases. Study Design: We reviewed all otosclerosis specimens meeting criteria from the temporal bone collection of the Massachusetts Eye and Ear Infirmary and 10 normal controls. Methods: Digital images were taken at predilection sites, followed by computer-assisted analysis. Canalicular area (CA), the aggregate of vascular spaces within bone, microvessel density (MVD), area, and depth were the main measures. Evidence of a direct connection between local vessels and the vasculature of the otosclerotic focus was also recorded for each specimen. Results: The average area (mm2) and depth (number of sections containing otosclerosis) of clinical lesions was significantly greater than histologic lesions. Total microvessel counts were significantly greater in clinical versus histologic lesions, and both clinical and histologic lesions contained significantly greater numbers of microvessels than the normal otic capsule. CA was also significantly higher in clinical lesions. MVD was slightly but not significantly higher in clinical lesions. Importantly, a direct connection between named vessels and the otosclerotic vasculature was significantly more frequent in clinical lesions. Conclusions: Computer-assisted quantification revealed significantly greater measures of angiogenesis in clinical versus histologic otosclerosis. Direct connection to adjacent vessels may support angiogenesis in this disease. Sustained angiogenesis may be an important determinant of clinical otosclerosis. [source] The prostatic environment suppresses growth of androgen-independent prostate cancer xenografts: An effect influenced by testosteroneTHE PROSTATE, Issue 11 2009Karin Jennbacken Abstract BACKGROUND Interactions between prostate cancer cells and their surrounding stroma play an important role in the growth and maintenance of prostate tumors. To elucidate this further, we investigated how growth of androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 prostate tumors was affected by different microenvironments and androgen levels. METHODS Tumor cells were implanted subcutaneously and orthotopically in intact and castrated immunodeficient mice. Orthotopic tumor growth was followed by magnetic resonance imaging (MRI). Gene expression in the tumors was evaluated by means of microarray analysis and microvessel density (MVD) was analyzed using immunohistochemistry. RESULTS The results showed that LNCaP-19 tumors grew more rapidly at the subcutaneous site than in the prostate, where tumors were obviously inhibited. Castration of the mice did not affect ectopic tumors but did result in increased tumor growth in the prostatic environment. This effect was reversed by testosterone treatment. In contrast to LNCaP-19, the LNCaP cells grew rapidly in the prostate and castration reduced tumor development. Gene expression analysis of LNCaP-19 tumors revealed an upregulation of genes, inhibiting tumor growth (including ADAMTS1, RGS2 and protocadherin 20) and a downregulation of genes, promoting cell adhesion and metastasis (including N-cadherin and NRCAM) in the slow-growing orthotopic tumors from intact mice. CONCLUSIONS The results show that the prostatic environment has a varying impact on AD and AI tumor xenografts. Data indicate that the androgen-stimulated prostatic environment limits growth of orthotopic AI tumors through induction of genes that inhibit tumor growth and suppression of genes that promote cell adhesion and metastasis. Prostate 69:1164,1175, 2009. © 2009 Wiley-Liss, Inc. [source] Reduction of human prostate tumor vascularity by the ,1-adrenoceptor antagonist terazosinTHE PROSTATE, Issue 2 2001Kaspar Keledjian Abstract BACKGROUND We previously demonstrated that the quinazoline-derived a1-adrenoceptor antagonists doxazosin and terazosin suppress prostate cancer growth via apoptosis induction. The aim of this study was to determine the potential effect of a1-adrenoceptor antagonists on tumor vascularity of the human prostate. METHODS A total of 34 men with benign prostatic hyperplasia (BPH) who have been on terazosin treatment (for the obstructive symptoms) were pathologically diagnosed with prostate cancer following surgery. These patients were stratified according to the length of treatment periods with terazosin into two groups, 1 week,6 months, and 6,17 months. The control group consisted of prostatectomy specimens from 25 untreated prostate cancer patients undergoing surgery for localized disease. Formalin-fixed, paraffin-embedded prostate specimens were analyzed for apoptosis (TUNEL assay), cell proliferation (Ki-67), microvessel density (MVD) (von Willebrand factor/Factor VIII), vascular endothelial growth factor (VEGF) expression, and prostate specific antigen (PSA) immunoreactivity. RESULTS A significant induction of apoptosis was observed among cancerous prostatic epithelial cells in the terazosin-treated, as compared to the untreated prostate cancer specimens, while there was no significant change in the proliferative index of the same tumor cell populations after treatment. Furthermore, terazosin resulted in a significant decrease in prostate tissue MVD compared with the untreated group (P,<,0.01), that correlated with the increased apoptotic index of the cancerous areas. Tissue PSA expression in the prostatic tumor foci was also markedly reduced after terazosin treatment, while no significant changes in VEGF expression were detected. CONCLUSIONS These findings provide the first evidence that terazosin, a quinazoline-based a1-blocker decreases prostate tumor vascularity. Our study has significant clinical implications in identifying selected ,1-adrenoceptor antagonists as potential anti-tumor agents with apoptotic and anti-angiogenic effects in the human prostate that can be exploited for the treatment of advanced prostate cancer. Prostate 48:71,78, 2001. © 2001 Wiley-Liss, Inc. [source] BS12 PREDICTIVE MARKERS FOR BREAST CANCER NEOADJUVANT CHEMOTHERAPYANZ JOURNAL OF SURGERY, Issue 2007S. Syed Purpose Although neoadjuvant chemotherapy (NACT) is routinely used in the management of breast cancer, there is no definitive way of predicting which patients are more likely to respond to a particular therapy. The aim of this study was to identify markers that can be used to predict tumor response to chemotherapy in breast cancer. Methodology We used immunohistochemistry to evaluate blood microvessel density (MVD) (CD31), tumor cell proliferation (Ki-67), anti-apoptotic marker (Bcl-2), ER and PR expression, and HER-2/neu expression in core biopsy samples (taken before chemotherapy) from patients with locally advanced breast cancer (n = 20), receiving neo-adjuvant chemotherapy {anthracycline-based regimen (FEC100) (n = 10) vs single agent taxane regimen (docetaxel) (n = 10), and correlated these factors with tumor response (as assessed clinically and by tumor imaging) after 4 cycles of treatment. Results Tumors expressing low levels of Bcl-2 showed significantly greater reduction in size to both taxane (P < 0.05) and anthracycline-based (P < 0.01) regimens, compared to tumors expressing high levels of Bcl-2. Further, HER-2/neu positive tumors showed significantly greater reduction in size to taxane regimen (P < 0.05), while estrogen receptor (ER) negative tumors showed a trend of greater reduction in size to anthracycline-based regimen (P = 0.06). Conclusions Bcl-2 and HER-2/neu expression may be useful markers to predict response to neoadjuvant chemotherapy in breast cancer. While subject numbers are still too low to draw firm conclusions, the current data indicates that HER-2/neu may specifically predict a positive tumor response to taxane regimen, and high Bcl-2 is a marker of chemoresistance. [source] | |||||||||||||||||||||||||||||||||||||