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BACKGROUND: Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival. MATERIALS AND METHODS: Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis. RESULTS: The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis (P < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (<28) than in patients with higher TAMs (>28) (P = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97-10.15], MVD (HR = 2.66; 95% CI: 1.27-5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27-3.12) significantly correlated with shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival. CONCLUSIONS: TAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.

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Osteonecrosis of the femoral head (ONFH) is a progressive disease with a complex etiology and unclear pathogenesis, resulting in severe hip pain and dysfunction mainly observed in young patients. Although total hip arthroplasty (THA) is the most effective treatment for patients with ONFH in the terminal stage, the results of THA in young patients or active populations are often not favorable, with some complications related to the prosthesis. With the development of biotechnology, an increasing number of studies pay attention to use of stem cells for the treatment of ONFH. Stem cells are characterized by the ability to self-renew and differentiate into multiple cell types, including differentiation into osteoblasts and endothelial cells to mediate bone repair and angiogenesis. Furthermore, stem cells can offer growth factors to promote blood supply in the necrotic regions by paracrine effects. Therefore, stem cell therapy has become one of the hip-preserving alternatives for ONFH. This review summarized the current trends in stem cell therapy for ONFH, from clinical applications to related basic research, and showed that an increasing number of studies have confirmed the effectiveness of stem cell therapy in ONFH. However, many unsolved problems and challenges in practical applications of stem cell therapy still exist, such as patient selection, standardized procedures, safety assessment, and the fate of transplanted cells in the body. Additional studies are required to find ideal cell sources, appropriate transplantation methods, and the optimal number of cells for transplantation.

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OBJECTIVE: To evaluate the impact of a luteinising hormone-releasing hormone (LHRH) agonist, goserelin acetate (GA), on surgical blood loss during transurethral resection of the prostate (TURP), as well as its histopathological effect on prostatic microvessel density (MVD). PATIENTS AND METHODS: Patients who underwent TURP due to benign prostatic enlargement (60-100 mL) were randomly subdivided into two equal groups according to whether they received preoperative GA administration (3.6 mg; group A) or not (group B). Evaluation parameters were operative time, weight of resected prostatic tissue, perioperative haematocrit (HCT) changes, estimation of intraoperative blood loss, and suburethral and stromal prostatic MVD. Effects of GA on prostate weight and any possible side-effects were also monitored. RESULTS: In all, 35 and 33 patients were included in groups A and B, respectively. Operative time and HCT values' changes were significantly less in group A (P < 0.05). Also, operative blood loss (both total and adjusted per weight of resected tissue) was lower in group A, at a mean (SD) of 178.13 (77.71) mL and 3.74 (1.52) mL/g vs 371.75 (91.09) mL and 8.59 (2.42) mL/g (P < 0.001). The median MVD in both suburethral [8 vs 11 vessels/high-power field (HPF)] and stromal tissues (9 vs 17 vessels/HPF) were significantly lower in group A (P < 0.001). Side-effects were minimal. CONCLUSION: A single dose of GA, a LHRH agonist, before TURP is safe and effective in reducing surgical blood loss. It significantly reduced MVD in both suburethral and stromal nodular prostatic tissues without regional discrepancy.

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While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8+ and CD4+ T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206+Tie2+ macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD). Notably, MVD was also increased at diagnosis in the BM of MGUS and SMM patients that subsequently progressed to MM when compared with MGUS and SMM that remained quiescent. These findings suggest a multistep pathogenic process in MM, in which the immune system may contribute to angiogenesis and disease progression. They also suggest initiating a large multicenter study to investigate MVD in asymptomatic patients as prognostic factor for the progression and outcome of this disease.

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BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine generation. VEGF plasma levels are elevated in circulation during tumor growth and bone marrow proliferative status. In this study, to investigate the role of VEGF expression in patients with aplastic anemia (AA), VEGF protein expression and microvessel density (MVD) were evaluated. METHODS: Immunohistochemical staining for detecting VEGF protein was performed by the labeled avidin-biotin method on the formalin-fixed and paraffin embedded bone marrow biopsy samples of 25 patients with severe AA and 10 normal controls. Microvessels were scored in at least 3 areas (x200 fields) of the highest MVD in representative sections of each bone marrow biopsy specimen using immunohistochemistry for CD34 antigen. RESULTS: In AA, megakaryocytes and histiocytes expressed less intense cytoplasmic VEGF than in control (P < 0.05). However, plasma cells had higher VEGF immunoreactivity in AA than in control. MVD was significantly lower in patients with AA (21.43+/-7.24), compared to controls (27.65+/-3.44) (P < 0.05). MVD had a strong correlation with bone marrow cellularity. Also, the degree of VEGF immunoreactivity was correlated with bone marrow cellularity and MVD. CONCLUSION: Angiogenesis as assessed by MVD and VEGF expression seems to have a role in the pathogenesis of AA.

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PURPOSE: This study was a retrospective evaluation of the correlation between the MVD (microvessel density) stained by anti-CD34 monoclonal antibodies, the expressions of p53 and Ki67 in gastric adenocarcinomas. The relationship between these markers and several clinicopathological parameters, if any, were also sort. METHODS: The study was performed on 82 patients diagnosed with gastric cancer, and operated on between July, 2000 and June, 2001. No neoadjuvant chemotherapy or radiation therapy was administered. Immunohistochemical staining was performed with monoclonal antibodies to CD34, p53, and Ki67 (DAKO, Copenhagen, Denmark). Independent t- and ANOVA tests were used to find any clinical correlation between the clinical parameters and MVD, from the immunohistochemical staining of the p53 and Ki67. A probability value (P value) less than 0.05 was considered as statistically significant. RESULTS: The mean values of MVD, p53 and Ki67 expressions (mean value+/-SD) were 38.5+/-15.2, 2.1+/-1.3, and 3.3+/-0.6, respectively. The maximal/minimal values were 153/4, 5/0 and 5/2. There was no apparent correlation found between the expressions of MVD, p53 and Ki67. Also, there was no correlation between the immunohistochemical staining and the clinicopathological parameters, such as age, sexual distribution, histological differentiation, N category and TNM stage. However, according to the depth of tumor invasion (T category), the MVD was found to be moreincreased in the early gastric adenocarcinomas (T1) than in advanced gastric adenocarcinomas (T2-4)(P=0.014). CONCLUSION: There was no apparent correlation between the expression of p53 and Ki67, or the clinicopathological parameters, such as age, sex, histological differentiation, T category, and N category and TNM stage. MVD was higher in the early gastric adenocarcinomas than in advanced gastric adenocarcinomas but further studies will be required to evaluate whether the MVD is a reliable prognostic factor in gastric adenocarcinomas.

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