Estrogen receptors: new perspectives in breast cancer management

The imbalance between proliferative and differentiative estrogenic effect, caused by quantitative and qualitative alteration of the estrogen receptor (ER) expression, may play a determinant role in mammary neoplastic transformation. Our studies demonstrate that ER levels are significantly higher in human mammary neoplastic tissues when compared to perineoplastic tissues and that increased ER expression is associated with ER gene hypomethylation. During progressive multifactorial carcinogene, ER overexpression may represent an early step in neoplastic transformation. In fact, high levels of ER represent good markers of differentiation and can predict the likelihood of benefiting from anti-estrogen therapy. Nevertheless, about 35% of ER-positive breast cancers are resistant to endocrine therapy and 10% of ER-negative tumors behave as hormone-sensitive tumors. Recent studies on ER mRNA variants, which naturally occur in human breast tumors, demonstrated mutations, deletions and alternative splicings, yielding deletions of exons 3, 4, 5 and 7. ER variants exhibited altered functions or changed the responsiveness to hormonal therapy. Analysis of these variants could be a useful parameter to better predict tumor responsiveness to anti-estrogen therapy. Recently, a regain of hormonal responsiveness by ER-negative breast cancer cells has been reported following ER gene transfection. However, estradiol treatment inhibits rather than stimulates cell growth as well as the metastatic and invasive potential of the ER gene transduced cells. Transfer of the ER gene may be considered as a new therapeutic approach in the management of hormone-independent breast cancer.     

A submerged new species of Cypella (Iridaceae), and a new section for the genus (s.str.)

Cypella aquatilis is described as a new species of the Iridaceae, occurring in the Brazilian states of Rio Grande do Sul, Santa Catarina and Parana. The plant is remarkable by being submersed in streamlets and rivers, and by the vegetative proliferation in the inflorescence. Additionally, a new section, Nais , with C. aquatilis as the type species, and the new name C. exilis Ravenna to replace the illegitimate C. gracilis (Kl.) Bak. are proposed.     

Lipido‐sterolic extract of Serenoa repens (LSESr,Permixon®) treatment affects human prostate cancer cell membrane organization

The molecular mechanism by which the lipido‐sterolic extract of Serenoa repens (LSESr, Permixon®) affects prostate cells remains to be fully elucidated. In androgen‐independent PC3 prostate cancer cells, the LSESr‐induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC‐1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 µg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol‐4,5‐bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre‐treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in ω6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in ω6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2–3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone‐independent status. J. Cell. Physiol. 219: 69–76, 2009. © 2008 Wiley‐Liss, Inc.     

Itysa and Lethia, two new genera of neotropical Iridaceae

The new genera Itysa and Lethia , of the Iridaceae, are proposed; the former with two species, I. gardneri (Bak.) Rav., from northeastern Brazil, and I. venezolensis Rav., from Venezuela, the former based on Calydorea gardneri Baker, the latter described as new. Lethia is based on Herbertia umbellata Klatt.     

SULFONAMIDE INHIBITION IN MONOCHRYSIS LUTHERP1

The effect of sulfonamides on growth of the chry-somonad, Monochrysis lutheri, in a synthetic sea-water medium was examined over a period of 14 days. The population increased at all sulfonamide concentrations during the first several days of incubation before inhibition became apparent. Inhibitory concentrations ranged from 0.01 to 1.0 mg%. Inhibition luas most pronounced in sulfathiazole; sulfamethazine, sulfapyridine, and sulfanilamide followed in decreasing order. p-Arninobenzoic acid (0.001-1.0 mg%) competitively reversed inhibition. Folic acid, thymine, adenine, and vitamin B₁₂ neither reversed the inhibition nor spared the requirement for p-aminobenzoic acid. The significance of the inhibition pattern and the potential use of antimetabolites in the marine environment were discussed.     

Taxonomical notes on the Chilean Cruciferae

The taxonomic status of some Chilean Cruciferae is elucidated, and new combinations in the genera Stenodraba Sch. and Hollermayera Sch. are established. Additionally a new section, Elatia , and two specific names to replace illegitimate binomials in Stenodraba are proposed.     

Growth of Pure Cultures of Marine Phytoplankton in the Presence of Toxicants

The effects of 17 toxicants on the growth of five species of algae in pure culture were studied. The two species displaying the greatest sensitivity to the action of each of the compounds tested were Monochrysis lutheri and Phaeodactylum tricornutum, and the most resistant species was Protococcus. Of eight different classes of toxicants tested, substituted urea compounds and a mercuric compound were most effective in inhibiting growth of all algal species at the lowest concentrations.     

Ultrasound-Guided Microinjection into the Mouse Forebrain In Utero at E9.5

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. However, because the uterine wall is opaque during early embryogenesis, the ability to target specific parts of the embryo for microinjection is greatly limited. Fortunately, high-frequency ultrasound imaging permits the generation of images that can be used in real time to guide a microinjection needle into the embryonic region of interest. Here we describe the use of such imaging to guide the injection of retroviral vectors into the ventricular system of the mouse forebrain at embryonic day (E) 9.5. This method uses a laparotomy to permit access to the uterine horns, and a specially designed plate that permits host embryos to be bathed in saline while they are imaged and injected. Successful surgeries often result in most or all of the injected embryos surviving to any subsequent time point of interest (embryonically or postnatally). The principles described here can be used with slight modifications to perform injections into the amnionic fluid of E8.5 embryos (thereby permitting infection along the anterior posterior extent of the neural tube, which has not yet closed), or into the ventricular system of the brain at E10.5/11.5. Furthermore, at mid-neurogenic ages (~E13.5), ultrasound imaging can be used direct injection into specific brain regions for viral infection or cell transplantation. The use of ultrasound imaging to guide in utero injections in mice is a very powerful technique that permits the molecular and cellular manipulation of mouse embryos in ways that would otherwise be exceptionally difficult if not impossible.