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.     

Genetic and enzymatic characterization of sphingomyelinase D isoforms from the North American fiddleback spiders Loxosceles boneti and Loxosceles reclusa.

In this study we report the isolation and characterization of several sphingomyelinase D isoforms from the venoms of the North American spiders Loxosceles boneti and Loxosceles reclusa, from Mexico and the United States, respectively. We have measured their enzymatic activity, their capacity to induce necrotic lesions in rabbits, cloned the cDNAs coding for the mature forms of two of the isoforms from L. boneti and two of L. reclusa based on N-terminal sequence information of the purified proteins, and performed a comprehensive comparison of the sequence data generated by us with that reported for other sphingomyelinase genes to date.     

p,p′-DDE,a DDT metabolite,induces proinflammatory molecules in human peripheral blood mononuclear cells “in vitro”

In a recent study, our group demonstrated that when peripheral blood mononuclear cells (PBMCs) were treated “in vitro” with p,p′-DDE, a DDT metabolite, an antioxidant response and biomarkers of inflammation were induced at the mRNA level, indicating a proinflammatory state. Thus, the aim of this study was to evaluate the induction of proinflammatory molecules at the protein level in PBMCs exposed to p,p′-DDE “in vitro”. The main finding was that “in vitro” exposure to p,p′-DDE enhanced the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6) at the protein level in PBMCs. We also observed COX-2 induction at the protein level. Considering that p,p′-DDE has been identified as a persistent metabolite and is frequently found in the population, it is important to evaluate early inflammation biomarkers in populations exposed to DDT and to estimate the true risk of inflammatory disease development.     

Tango7 directs cellular remodeling by the Drosophila apoptosome

It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. Here we report that Tango7 collaborates with the Drosophila apoptosome to drive a caspase-dependent remodeling process needed to resolve individual sperm from a syncytium. In these cells, Tango7 is required for caspase activity and localizes to the active apoptosome compartment via its C terminus. Furthermore, Tango7 directly stimulates the activity of this complex in vitro. We propose that Tango7 specifies the Drosophila apoptosome as an effector of cellular remodeling.     

The ACE DD genotype and D-allele are associated with exceptional longevity: A meta-analysis

The ACE I/D polymorphism has been associated with longevity, although not consistently. The objective of this study was to detect the possible unequal distribution of the alleles and genotypes of this polymorphism among centenarians and younger segments of the population. Relevant data were extracted from studies in the literature, comparing genotype and allele frequencies between centenarians and younger controls. The association of ACE I/D polymorphism with exceptional longevity was analyzed in a total of 1803 centenarians and 10,484 controls using the chi-square test with the Yates correction. We conducted combined analyses for all ethnic groups studied in the literature (Caucasian, Chinese and Korean) as well as for Caucasians only. The DD genotype (odds ratio (OR): 1.25 (95% confidence interval (CI): 1.02–1.54), P = 0.032) and the D-allele were more frequent in Caucasian centenarians compared with their younger controls (OR: 1.16 (95% CI: 1.05–1.28), P < 0.001). Similar findings were obtained when all ethnic origin groups were included in the analyses, with no evidence of publication bias or heterogeneity (P > 0.05). The present meta-analysis indicates that the ACE D-allele and the DD genotype might confer a modest, albeit significant advantage to reach exceptional longevity.     

Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs

Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds.     

FGFR1 amplification and the progression of non-invasive to invasive breast cancer

A recent prospective clinical trial provides further evidence that breast cancers arising in germline BRCA1 mutation carriers are highly sensitive to cisplatin chemotherapy. The potential significance of these data for the management of patients with BRCA1-related and BRCA2-related breast cancer is discussed.