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Dan Green

Publications and source records attributed to Dan Green.

5 recordsLinked to original sources

Angiogenesis in the bone marrow of patients with breast cancer.

PURPOSE: Pathologic angiogenesis has been correlated with tumor growth, dissemination, metastasis, and prognosis in solid tumors including breast cancer. Angiogenesis has also been implicated in the pathophysiology of, and shown to be a therapeutic target in tumors arising in the bone marrow. The status of angiogenesis in the bone marrow of breast cancer patients is unknown. The aim of this study was to estimate the extent of bone marrow angiogenesis in this subset of patients. EXPERIMENTAL DESIGN: We studied 42 women with breast cancer in whom a bone marrow biopsy was done. Bone marrow samples were sorted according to their infiltration status by breast cancer cells. In all bone marrow sections, blood vessels were highlighted by staining endothelial cells with an antibody directed against the CD34-related antigen. A hematopathologist blind to the status of infiltration of breast cancer did the bone marrow vessel count. RESULTS: Nineteen patients (45%) had bone marrow metastasis. The bone marrow microvessel density was significantly higher in patients with bone marrow metastases compared with patients without bone marrow metastases (P < 0.0005). Median bone marrow microvessel density was 2 for the negative bone marrow group, and 15 for the positive bone marrow group. An increased microvessel density was correlated with presence of disease at last follow-up. CONCLUSIONS: This is the first study showing that bone marrow microvessel density is significantly higher in breast cancer patients with bone marrow metastases, when compared with breast cancer patients without evidence of bone marrow metastatic disease. Further research is needed to shed light into the prognostic and therapeutic relevance of this finding.

Adult↗

Hemispherical gradient coils for magnetic resonance imaging.

Hemispherical gradient coils offer an open geometry that is well suited to imaging of the human brain. The windings of a hemispherical gradient coil are on average closer to the target region than those of a comparable cylindrical coil, and consequently hemispherical coils can produce higher efficiency at fixed inductance. The mathematical formalism needed for the design of hemispherical gradient coils is described here, including expressions relating the current distribution on the hemisphere to the magnetic field generated, as well as the stored energy and power dissipation. In addition, expressions for the torque experienced by the current distribution in the presence of the main magnetic field have been derived and used to develop an approach allowing the design of torque-balanced, hemispherical transverse gradient coils. Hemispherical coil designs suitable for brain imaging are presented and shown to have improved performance compared with their cylindrical counterparts. Small, prototype, hemispherical z- and x-gradient coils have been constructed and tested in phase-mapping experiments at 3 T. The experimental results show good agreement with theoretical predictions, validating the mathematical expressions used in the coil design process. The formalism also allows the design of coils wound on a complete spherical surface, and the performance of such coils is additionally described here.

Brain Mapping↗

E-cadherin expression in sporadic gastric cancer from Mexico: exon 8 and 9 deletions are infrequent events associated with poor survival.

Aberrant expression and mutation of E-cadherin is frequent in gastric carcinoma (GC) especially of the diffuse type. The frequency of CDH1 (gene encoding E-cadherin) mutation in populations with high incidence of diffuse GC and its prognostic significance is unknown. One hundred seventy-seven gastrectomies from Mexican mestizo patients with intestinal (53), mixed (55), or diffuse (69) GC were included. In addition, 101 endoscopic biopsies from patients with GC not subjected to surgery were analyzed. Immunohistochemistry against wild-type E-cadherin (clone 36) and against 2 mutation-specific antibodies (MSA) recognizing mutant CDH1 lacking exon-8 (del 8) or exon-9 (del 9) were performed. Staining was correlated with histotype, tumor node metastasis stage, and follow-up. Abnormal or absent E-cadherin expression (clone 36) was identified in 84% GC, predominantly in diffuse or mixed tumors (P = 0.004) in advanced stages (P = 0.003). No survival differences at 1 and 2 years were observed among patients showing normal, abnormal, or absent wild type E-cadherin expression. Overall reactivity with the MSA was observed in 10 (5.6%) patients who were treated with surgery. In 140 patients, dead from the disease or alive with the disease, the survival at 1 and 2 years was 37% versus 17% and 14% versus 0 for patients without and with del 8/9 positivity, respectively (log rank P = 0.01). Biopsies from patients with inoperable-GC (101) rendered 5 (4.95%) with del 8 or 9 immunoreactivity. Abnormal E-cadherin expression is frequent in GC. However, exon 8 or 9 deletions were observed in only 5.3% tumors in this series from Mexico, at a lower rate than previously published, but associated with a worse prognosis.

Adolescent↗

Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system.

The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied.

Adenocarcinoma↗

Adenocarcinoma of the stomach: univariate and multivariate analysis of factors associated with survival.

Gastric cancer is the most frequent tumor of the digestive tract in Mexico. Most patients are diagnosed at advanced stages, and fatal outcome is expected. One hundred fifty patient charts were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic and treatment variables on survival. Most patients (75%) were at advanced stages, harboring poorly differentiated tumors. Surgery, mostly palliative, was performed on 114 patients. Chemotherapy was administered to 47 patients. On univariate analysis, significant prognostic factors were TNM stage, chemotherapy, surgical attempt, performance status, histology, and tumor site (p < 0.001). On multivariate analysis, independent prognostic factors were TNM stage, histology, tumor site, surgical attempt, and chemotherapy (p < 0.01). Median survival for patients with palliative or adjuvant chemotherapy was 11.4 and 10.4 months, respectively, compared with +/- 3 months for patients with no chemotherapy (p < 0.03). Nonsurgical patients receiving chemotherapy survived 5.4 months versus 1.1 months for those without chemotherapy. The favorable influence of chemotherapy persisted after a stratified analysis of subgroups eliminating potential biases. We identified prognostic factors for survival. Chemotherapy should be considered even for advanced-stage patients with either adjuvant or palliative attempts, because we consistently found a favorable impact on the median survival time. However, phase III prospective randomized trials are awaited.

Adenocarcinoma↗