Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Epithelial-mesenchymal transition and mesenchymal-epithelial transition are essential for the acquisition of stem cell properties in hTERT-immortalised oral epithelial cells

BACKGROUND INFORMATION: Evidence has shown that mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are linked to stem cell properties. We currently lack a model showing how the occurrence of MET and EMT in immortalised cells influences the maintenance of stem cell properties. Thus, we established a project aiming to investigate the roles of EMT and MET in the acquisition of stem cell properties in immortalised oral epithelial cells. RESULTS: In this study, a retroviral transfection vector (pLXSN-hTERT) was used to immortalise oral epithelial cells by insertion of the hTERT gene (hTERT(+)-oral mucosal epithelial cell line [OME]). The protein and RNA expression of EMT transcriptional factors (Snail, Slug and Twist), their downstream markers (E-cadherin and N-cadherin) and embryonic stem cell markers (OCT4, Nanog and Sox2) were studied by reverse transcription PCR and Western blots in these cells. Some EMT markers were detected at both mRNA and protein levels. Adipocytes and bone cells were noted in the multi-differentiation assay, showing that the immortal cells underwent EMT. The differentiation assay for hTERT(+)-OME cells revealed the recovery of epithelial phenotypes, implicating the presence of MET. The stem cell properties were confirmed by the detection of appropriate markers. Altered expression of alpha-tubulin and gamma-tubulin in both two-dimensional-cultured (without serum) and three-dimensional-cultured hTERT(+)-OME spheroids indicated the re-programming of cytoskeleton proteins which is attributed to MET processes in hTERT(+)-OME cells. CONCLUSIONS: EMT and MET are essential for hTERT-immortalised cells to maintain their epithelial stem cell properties.

Dual acquisition of 18F-FMISO and 18F-FDOPA

Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

Variation in acquisition of Fiji disease virus by Perkinsiella saccharicida (Hemiptera: Delphacidae).

Fiji leaf gall, caused the Fiji disease virus (genus Fijivirus, family Reoviridae, FDV), is a serious disease of sugarcane, Saccharum officinarum L., in Australia and several other Asia-Pacific countries. In Australia FDV is transmitted only by the planthopper Perkinsiella saccharicida Kirkaldy (Hemiptera: Delphacidae), in a propagative manner. Successful transmission of FDV by single planthoppers confined to individual virus free plants is highly variable, even under controlled conditions. The research reported here addresses two possible sources of this variation: 1) gender, wing form, and life stage of the planthopper; and 2) genotype of the source plant. The acquisition of FDV by macropterous males, macropterous females, brachypterous females, and nymphs of P. saccharicida from infected plants was investigated using reverse transcription-polymerase chain reaction to diagnose FDV infection in the vector. The proportion of individuals infected with FDV was not statistically related to life stage, gender, or adult wing form of the vector. The acquisition of FDV by P. saccharicida from four cultivars of sugarcane was compared to assess the influence of plant genotype on acquisition. Those planthopper populations reared on diseased 'NCo310' plants had twice as many infected planthoppers as those reared on 'Q110', 'WD1', and 'WD2'. Therefore, variation in FDV acquisition in this system is not the result of variation in the gender, wing form and life stage of the P. saccharicida vectors. The cultivar used as the source plant to rear vector populations does affect the proportion of infected planthoppers in a population.

Acquisition of focus by normal hearing and Cochlear implanted children

Two experiments investigated the perception of compound vs. phrasal stress and narrow focus in normally hearing children and children with Cochlear Implants (CI). Additionally, we investigated whether musical experience would predict children’s performance in these tasks. The results showed no difference between CI and normal-hearing (NH) children in either experiment. However, whereas we found no clear effect of age in the children’s stress detection, there was a clear age related trajectory in the ability to recognise (narrow) focus. Moreover, this trend was similar to what has been found previously for English children. Importantly, prior music experience was significantly linked to CI children’s perception of focus.

Compressed acquisition of correlated signals

Distributed compressed sensing exploits information redundancy, inbuilt in multi-signal ensembles with interas well as intra-signal correlations, to reconstruct undersampled signals. In this paper we revisit this problem, albeit from a different perspective, of taking streaming data, from several correlated sources, as input to a real time system which, without any a priori information, incrementally learns and admits each source into the system.

Inactivation of the Bacterial RNA Polymerase Due to Acquisition of Secondary Structure by the omega Subunit

The widely conserved omega subunit encoded by rpoZ is the smallest subunit of Escherichia coli RNA polymerase (RNAP) but is dispensable for bacterial growth. Function of omega is known to be substituted by GroEL in omega-null strain, which thus does not exhibit a discernable phenotype. In this work, we report isolation of omega variants whose expression in vivo leads to a dominant lethal phenotype. Studies show that in contrast to omega, which is largely unstructured, omega mutants display substantial acquisition of secondary structure. By detailed study with one of the mutants, omega(6) bearing N60D substitution, the mechanism of lethality has been deciphered. Biochemical analysis reveals that omega(6) binds to beta ` subunit in vitro with greater affinity than that of omega. The reconstituted RNAP holoenzyme in the presence of omega(6) in vitro is defective in transcription initiation. Formation of a faulty RNAP in the presence of mutant omega results in death of the cell. Furthermore, lethality of omega(6) is relieved in cells expressing the rpoC2112 allele encoding beta ` (2112), a variant beta ` bearing Y457S substitution, immediately adjacent to the beta ` catalytic center. Our results suggest that the enhanced omega(6)-beta ` interaction may perturb the plasticity of the RNAP active center, implicating a role for omega and its flexible state.

Sensory cues employed for the acquisition of familiarity-dependent recognition of a shoal of conspecifics by climbing perch (Anabas testudineus Bloch)

In this study we showed that a freshwater fish, the climbing perch (Anabas testudineus) is incapable of using chemical communication but employs visual cues to acquire familiarity and distinguish a familiar group of conspecifics from an unfamiliar one. Moreover, the isolation of olfactory signals from visual cues did not affect the recognition and preference for a familiar shoal in this species.

Simultaneous acquisition of three NMR spectra in a single experiment for rapid resonance assignments in metabolomics

NMR-based approach to metabolomics typically involves the collection of two-dimensional (2D) heteronuclear correlation spectra for identification and assignment of metabolites. In case of spectral overlap, a 3D spectrum becomes necessary, which is hampered by slow data acquisition for achieving sufficient resolution. We describe here a method to simultaneously acquire three spectra (one 3D and two 2D) in a single data set, which is based on a combination of different fast data acquisition techniques such as G-matrix Fourier transform (GFT) NMR spectroscopy, parallel data acquisition and non-uniform sampling. The following spectra are acquired simultaneously: (1) C-13 multiplicity edited GFT (3,2)D HSQC-TOCSY, (2) 2D H-1- H-1] TOCSY and (3) 2D C-13- H-1] HETCOR. The spectra are obtained at high resolution and provide high-dimensional spectral information for resolving ambiguities. While the GFT spectrum has been shown previously to provide good resolution, the editing of spin systems based on their CH multiplicities further resolves the ambiguities for resonance assignments. The experiment is demonstrated on a mixture of 21 metabolites commonly observed in metabolomics. The spectra were acquired at natural abundance of C-13. This is the first application of a combination of three fast NMR methods for small molecules and opens up new avenues for high-throughput approaches for NMR-based metabolomics.

A new method for the acquisition of ultrasonic strain image volumes.

This article presents a new method for acquiring three-dimensional (3-D) volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. Acquisition of a volume takes 15-20 s. A strain volume is then calculated by comparing frame pairs throughout the sequence. The method uses strain quality estimates to automatically pick out high quality frame pairs, and so does not require careful control of the axial compression. In a series of in vitro and in vivo experiments, we quantify the image quality of the new method and also assess its ease of use. Results are compared with those for the current best alternative, which calculates strain between two complete volumes. The volume pair approach can produce high quality data, but skillful scanning is required to acquire two volumes with appropriate relative strain. In the new method, the automatic quality-weighted selection of image pairs overcomes this difficulty and the method produces superior quality images with a relatively relaxed scanning technique.

The acquisition of Tense and Aspect in Spanish

280 p.

The acquisition of gender agreement in L3 English by Basque/Spanish bilinguals

211 p.