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991.
Carolin Bock Brigitte Rack Christina Kuhn Simone Hofmann Charlotte Finkenzeller Bernadette Jäger Udo Jeschke Sophie F. Doisneau-Sixou 《Translational oncology》2012,5(6):475-485
Hormone therapy and anti-ErbB2 therapies are prescribed according to the hormone receptor [estrogen receptor α (ERα)/progesterone receptor] and ErbB2 status of the initial tumor, but it appears that circulating tumor cells (CTCs) and, consequently, the metastatic cells may have a different receptor status. As an attempt to meet the crucial need for identification of the subpopulation of patients that will benefit from more individualized therapies, rapidly evolving therapies should allow a profiling of the tumors and/or of the CTCs. We established a triple fluorescence staining using eight cell lines to visualize the CTCs (cytokeratin detection) and then to define their individual ERα and ErbB2 status. Afterward, we used this method for blood samples from 26 metastatic breast cancer patients. We identified major differences of ERα levels between the cell lines and even within one cell line. For the metastatic patients, we detected and characterized CTCs in 38.5% of the patients with a total of 92 CTCs. We could demonstrate that at least 69.6% of the CTCs exhibit an ERα and/or ErbB2 status different from the status of the primary tumor and that the CTCs from only 30% of the patients had no change of receptor status. Strikingly, heterogeneities of the status, aggregation, and size clearly appear within the CTCs. The data we generated outline the importance of a profiling not only of tumors but also of CTCs to establish individualized treatments. CTCs may then appear as new prognosis and treatment marker for both metastatic and adjuvant breast cancers. 相似文献
992.
Christina J. Schier Regina A. Mangieri Geoffrey A. Dilly Rueben A. Gonzales 《Journal of visualized experiments : JoVE》2012,(67)
Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol. However, ethanol is typically self-administered orally, rather than intravenously like many other drugs of abuse. The pharmacokinetics of orally administered drugs are more complex than intravenously administered drugs. Because understanding the relationship between the pharmacological and behavioral effects of ethanol requires knowledge of the time course of ethanol reaching the brain during and after drinking, we use in vivo microdialysis and gas chromatography with flame ionization detection to monitor brain dialysate ethanol concentrations over time. Combined microdialysis-behavioral experiments involve the use of several techniques. In this article, stereotaxic surgery, behavioral training and microdialysis, which can be adapted to test a multitude of self-administration and neurochemical centered hypotheses, are included only to illustrate how they relate to the subsequent phases of sample collection and dialysate ethanol analysis. Dialysate ethanol concentration analysis via gas chromatography with flame-ionization detection, which is specific to ethanol studies, is described in detail. Data produced by these methods reveal the pattern of ethanol reaching the brain during the self-administration procedure, and when paired with neurochemical analysis of the same dialysate samples, allows conclusions to be made regarding the pharmacological and behavioral effects of ethanol. 相似文献
993.
994.
Gargalionis AN Piperi C Adamopoulos C Papavassiliou AG 《The international journal of biochemistry & cell biology》2012,44(8):1276-1289
Epigenetic regulation of gene expression has provided colorectal cancer (CRC) pathogenesis with an additional trait during the past decade. In particular, histone post-translational modifications set up a major component of this process dictating chromatin status and recruiting non-histone proteins in complexes formed to "handle DNA". In CRC, histone marks of aberrant acetylation and methylation levels on specific residues have been revealed, along with a plethora of deregulated enzymes that catalyze these reactions. Mutations, deletions or altered expression patterns transform the function of several histone-modifying proteins, further supporting the crucial role of epigenetic effectors in CRC oncogenesis, being closely associated to inactivation of tumor suppressor genes. Elucidation of the biochemical basis of these new tumorigenic mechanisms allows novel potential prognostic factors to come into play. Moreover, the detection of these changes even in early stages of the multistep CRC process, along with the reversible nature of these mechanisms and the technical capability to detect such alterations in cancer cells, places this group of covalent modifications as a further potential asset for clinical diagnosis or treatment of CRC. This review underlines the biochemistry of histone modifications and the potential regulatory role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the underlying mechanisms of the emerging epigenetic interplay along with the chemical compounds that are candidates for clinical use are discussed, offering new insights for further investigation of key histone enzymes and new therapeutic targets. 相似文献
995.
A milestone in understanding a globally significant mechanism of marine bioinvasions was published 25 years ago. The transformative
paper on ballast water provided a baseline of patterns, processes and predictions of marine introductions, underpinned a dramatic
increase in research on the topic, and presented a foundational insight for an international approach to vector management.
The 25 year anniversary of JT Carlton’s ‘Transoceanic and interoceanic dispersal of coastal marine organisms: the biology
of ballast water’ coincides with an International Maritime Organization (IMO) convention for management of ballast water that
has not been fully ratified. The emergence of ship biofouling as a vector of management concern worldwide has also prompted
renewed efforts to reduce species transfers by ships through new policy initiatives. 相似文献
996.
Christina A. Olson Karen H. Beard David N. Koons William C. Pitt 《Biological invasions》2012,14(4):889-900
Two nonnative Caribbean frogs, the Puerto Rican coqui and the Cuban greenhouse frog, recently invaded Hawaii. Because of its
louder breeding call, management efforts have focused on the coqui, while little has been done to address the more cryptic
greenhouse frog, even though it may be as widespread and have similar ecological impacts. The goal of this research was to
determine the distribution and detection probability of both species on the island of Hawaii. We conducted a breeding call
presence/absence survey at 446 sites every 2 km along major road networks. We re-surveyed 125 sites twice to determine detection
and occupancy probabilities. Greenhouse frog detection probabilities (0.24, 0.29, 0.48, for each of the three visits, respectively)
were lower than coqui detection probabilities (0.58, 0.73, 0.50, respectively) and increased with visits while those of the
coqui did not. Greenhouse frog detection probabilities were lower in the presence of coquis for the first two surveys (0.12,
0.14) than in sites with greenhouse frogs alone (0.41), while greenhouse frogs had no effect on the detection of coquis. Site
occupancy estimates for the greenhouse and coqui frog were 0.35 and 0.31, respectively, suggesting the species are similarly
widespread. Results suggest multiple visits to sites are required to detect the greenhouse frog. Furthermore, results suggest
that accounting for detectability is essential when determining the extent of invasion of cryptic species. 相似文献
997.
An N-terminal dileucine motif directs two-pore channels to the tonoplast of plant cells 总被引:1,自引:0,他引:1
Two‐pore channels (TPCs) constitute a family of endolysosomal cation channels with functions in Ca2+ signaling. We used a mutational analysis to investigate the role of channel domains for the trafficking of the Arabidopsis TPC1 to the tonoplast, a process that is generally not well understood in plants. The results show that the soluble C‐terminus was not essential for targeting but for channel function, while further C‐terminal truncations of two or more transmembrane domains impaired protein trafficking. An N‐terminal dileucine motif (EDPLI) proved to be critical for vacuolar targeting of TPC1, which was independent of the adaptor protein AP‐3. Deletion or mutation of this sorting motif, which is conserved among TPCs caused redirection of the protein transport to the plasma membrane. An N‐terminal region with a predicted α‐helical structure was shown to support efficient vacuolar trafficking and was essential for TPC1 function. Similar to their localization in mammalian endosomes and lysosomes, MmTPC1 and MmTPC2 were targeted to small organelles and the membrane of the lytic vacuole, respectively, when expressed in plant cells. These results shed new light on the largely uncharacterized sorting signals of plant tonoplast proteins and reveal similarities between the targeting machinery of plants and mammals. 相似文献
998.
OCRL1 Modulates Cilia Length in Renal Epithelial Cells 总被引:1,自引:0,他引:1
Rbaibi Y Cui S Mo D Carattino M Rohatgi R Satlin LM Szalinski CM Swanhart LM Fölsch H Hukriede NA Weisz OA 《Traffic (Copenhagen, Denmark)》2012,13(9):1295-1305
Lowe syndrome is an X-linked disorder characterized by cataracts at birth, mental retardation and progressive renal malfunction that results from loss of function of the OCRL1 (oculocerebrorenal syndrome of Lowe) protein. OCRL1 is a lipid phosphatase that converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. The renal pathogenesis of Lowe syndrome patients has been suggested to result from alterations in membrane trafficking, but this cannot fully explain the disease progression. We found that knockdown of OCRL1 in zebrafish caused developmental defects consistent with disruption of ciliary function, including body axis curvature, pericardial edema, hydrocephaly and impaired renal clearance. In addition, cilia in the proximal tubule of the zebrafish pronephric kidney were longer in ocrl morphant embryos. We also found that knockdown of OCRL1 in polarized renal epithelial cells caused elongation of the primary cilium and disrupted formation of cysts in three-dimensional cultures. Calcium release in response to ATP was blunted in OCRL1 knockdown cells, suggesting changes in signaling that could lead to altered cell function. Our results suggest a new role for OCRL1 in renal epithelial cell function that could contribute to the pathogenesis of Lowe syndrome. 相似文献
999.
The lysosomal membrane protein type 2 is a novel identified lysosomal sorting receptor for β-glucocerebrosidase (GC). Mutations in both genes underlie human pathologies causing action myoclonus-renal failure syndrome (AMRF) and Gaucher disease (GD), respectively. We now demonstrate that the lumenal acidification mediated by the vacuolar (H(+) )-ATPase triggers the dissociation of LIMP-2 and GC in late endosomal/lysosomal compartments. Moreover, we identified a single histidine residue in LIMP-2 that is necessary for LIMP-2 and GC binding. This residue is in close proximity to a proposed coiled-coil domain, which determines the binding to GC and may function as a critical pH sensor. 相似文献
1000.