Insights into the epithelial mesenchymal transition phenotype in cancer of unknown primary from a global microRNA profiling study

PURPOSE: We sought to study the microRNA regulation of epithelial mesenchymal transition (EMT), the acquisition of migratory, mesenchymal-like properties of epithelial cells, in cancer of unknown primary (CUP). PATIENTS AND METHODS: We studied the global expression profile of 982 microRNAs by means of microarray technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative. RESULTS: EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level in the EMT-positive cases without, however, reaching statistical significance. MiR-205, a squamous tissue-specific marker, was very variable in the data set. Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR-200 family exhibited a trend of downregulation in EMT-positive cases. A similar pattern of miRNA expression was detected when the comparison took place between EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203, miR-205 and miR-200c were numerically downregulated in those tumours with high expression of the EMT marker N-cadherin. CONCLUSIONS: The EMT-suppressive miR-203 and miR-200 family were consistently but non-significantly downregulated in CUP with the EMT phenotype. A larger study is warranted to further explore the role of microRNAs in CUP (AU)

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The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system.

BACKGROUND: The oxaliplatin (ΟΧΑ)-based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ-based chemotherapy on the ANS. METHODS: We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3-4 months and 6-8 months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR). RESULTS: The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both P < 0.001), while patients had more often diastolic OH at the 6-8 month evaluation compared to baseline (P = 0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (P = 0.036 and P = 0.020). CONCLUSIONS: Oxaliplatin-based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.

Insights into the epithelial mesenchymal transition phenotype in cancer of unknown primary from a global microRNA profiling study.

PURPOSE: We sought to study the microRNA regulation of epithelial mesenchymal transition (EMT), the acquisition of migratory, mesenchymal-like properties of epithelial cells, in cancer of unknown primary (CUP). PATIENTS AND METHODS: We studied the global expression profile of 982 microRNAs by means of microarray technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative. RESULTS: EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level in the EMT-positive cases without, however, reaching statistical significance. MiR-205, a squamous tissue-specific marker, was very variable in the data set. Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR-200 family exhibited a trend of downregulation in EMT-positive cases. A similar pattern of miRNA expression was detected when the comparison took place between EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203, miR-205 and miR-200c were numerically downregulated in those tumours with high expression of the EMT marker N-cadherin. CONCLUSIONS: The EMT-suppressive miR-203 and miR-200 family were consistently but non-significantly downregulated in CUP with the EMT phenotype. A larger study is warranted to further explore the role of microRNAs in CUP.

Undocumented migrants in Greece: issues of regularization.

PIP: This article studies migration from Albania to Greece and schematically looks at the socioeconomic integration and/or exclusion of Albanians. It explores the issue of regularization: first, using the game-theoretic framework, it provides an explanation for the choices made by the Greek government; second, it outlines efforts made towards the regularization of undocumented migrants in Greece. In an effort to explain the Greek government choices with the regards to the regularization of migrants, a number of possibilities or outcomes of both regularization and non-regularization, which depend on the relative magnitudes of payoffs to employers and government were established. Attempts from the Greek government to regularize migrants include passing a framework law specifying procedures for regularization. This law, if successfully enforced, will increase the cost of labor to Greek firms; and if implemented in the years to come, the regularization rate may be low because migrants are given only a temporary status. In addition, there is a possibility that the required procedures would not be followed properly. Moreover, the absence of political debate has not helped ease continued foot-dragging in dealing with an issue so critical for Greece. This has contributed to Greece being seen as unofficially encouraging illegal migration so as to keep wages down and boost economic growth.^ieng

Albanian and Polish undocumented workers in Greece: a comparative analysis.

PIP: "This article deals with the migration of undocumented workers from Albania and Poland to Greece. Its underlying assumption is that migration from the former post-communist countries to Greece is not a homogeneous phenomenon, thus allowing for a distinction and comparison between the migration waves from Poland and Albania to Greece. The article shows that economic migration from Albania and Poland to Greece is primarily an economically triggered phenomenon which results from both individual rational choices and social, structural settings, and which verifies a general tendency of mass flows, characteristic of the era of disorganized capitalism." (EXCERPT)^ieng

Immigration to Greece: a critical evaluation of Greek policy.

"In the light of the EU's interest in the movement of labour within the Union, the first part of this article looks at the character of Greek migrant labour with the aim of providing an overview of changes in the flow of migrant labour into Greece and of the policies adopted in relation to immigrant labour. It discusses the failure of the Greek government to formulate strategic measures to combat illegal immigration...and the limited (if any) efforts being made to aid the integration of Albanians. The second part of the article concentrates on [the experiences of] Albanian migrant labourers in Greece....[It] also assesses the similarities and differences in the employment positions of Albanian men and women in Greece and the way in which mechanisms of marginalisation differently affect these two categories."

Pyrolysing insecticidal coils: air pollution by polycyclic aromatic hydrocarbons and other mutagens detected by the Salmonella/microsome test.

Pyrolysing insecticidal coils, which are used commonly for their evaporative release of insecticidal amounts of pyrethrins, have been investigated with respect to the emission of airborne particles, their mutagenic activity in the Salmonella/microsome mutagenicity test and their polycyclic aromatic hydrocarbons (PAH) content. Emitted particles contain compounds that are mutagenic in the absence of exogenous activation, as well as components that require mammalian activation. The particles also contain a range of PAH, but their concentration cannot account for the mutagenic response with mammalian activation. The use of pyrolysing insecticidal coils in semi-enclosed spaces may cause air pollution by releasing mutagenic and carcinogenic compounds that are of a magnitude similar to that found in other air pollution situations.

Mutagenicity assay of emission extracts from wood stoves: comparison with other emission parameters.

The emission from wood stoves of several types of air pollutants has been measured under standardized burning conditions with emphasis on the amount of organic compounds and determination of the mutagenic activity with the Salmonella/microsome assay. The study corroborates earlier findings that conventional wood stoves can be a significant source of hydrocarbon and tar compounds in the ambient air. The emission of mutagenic compounds comprise both compounds requiring mammalian activation and compounds which are active in the test without exogenous activation. The mutagenicity tests show that nitroaromatic compounds are present in wood stove emissions, although the emission of nitrogen oxides is low. A wood stove constructed using the downdraft principle emitted much less hydrocarbons and tar, less mutagenic components and slightly less carbon monoxide than conventional wood stoves.

Efflux of cyclic guanosine 3',5'-monophosphate from cerebellar slices stimulated by L-glutamate or high K+ or N-methyl-N'-nitro-N-nitrosoguanidine.

The efflux of cyclic guanosine 3',5'-monophosphate (cGMP) was studied from rat cerebellar slices which were stimulated by L-glutamate (1 mM), or by depolarizing concentrations of K+ (60 mM) or by the nitroso compound, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Via different mechanisms these agents stimulated cGMP synthesis producing several fold elevation of the cGMP content of the tissue slices. Simultaneously with the elevation of the intracellular (intra slice) concentrations of cGMP, a temperature-and time-dependent efflux of cGMP into the medium took place. This efflux was maximal at 5 min and could be inhibited by the known inhibitor of anion transport, probenecid, in a concentration-dependent manner. The results suggest the presence of an efflux system for cGMP, which may participate together with the well-characterized 3',5'-cyclic nucleotide phosphodiesterases in reduction of elevated cGMP levels.

Environmental tobacco smoke: comparative characterization by mutagenicity assays of sidestream and mainstream cigarette smoke.

Mainstream cigarette smoke particles were collected by means of a smoking machine, and sidestream particles were collected from the room in which the smoking took place. The particles were extracted by sonication with acetone, and the extracts were solvent-exchanged to dimethyl sulfoxide. The samples were tested for mutagenicity in the Ames Salmonella/microsome assay. The mainstream extract is preferentially mutagenic in the presence of S9, with about 30,000 revertants/cigarette in TA98, but has little or no activity in its absence. The sidestream extract is also mutagenic in the presence of S9 with TA98, and this activity is mainly due to basic compounds. Sidestream smoke is also significantly mutagenic in the absence of S9 in the strain TA100 as well as in TA97 and TA104. This "direct" activity is due to components that are labile. The response of sidestream particles is 10,000-20,000 revertants/cigarette in TA98 + S9 and TA100-S9 when the collection is performed in a room where the particle concentration is modulated by deposition to surfaces. Sidestream particles collected on glass fiber filter and by electrostatic precipitation (ESP) with a commercial air cleaning device gave essentially the same mutagenic response, showing that ESP sampling may be an alternative to filter sampling for environmental tobacco smoke (ETS) in indoor environments. ESP sampling in children's rooms in smoking and nonsmoking homes showed that 5-10% of the tobacco smoke emitted in the smoking homes entered the child's room, demonstrating that diffusion of pollutants is faster than ventilation in modern buildings with low ventilation rates.

Short-term bioassays of fractionated emission samples from wood combustion.

Extracts of an emission sample from wood burning, consisting of particles and volatiles, have been fractionated on an HPLC silica gel column into five fractions of increasing polarity. Nonfractionated samples and the individual fractions have been tested in three different short-term bioassays: the Ames Salmonella assay, the sister chromatid exchange (SCE) induction-test in Chinese hamster ovary cells (CHO), and the cell transformation test on Syrian hamster embryo (SHE) cells. Most of the total activity was found in the volatile part of the sample with all three bioassays, whereas the particle extract had the highest activity per unit mass extracted. The second most polar fraction contained most of the mass and was also highly active in all assays. The most polar fraction was very potent in the Salmonella assay, but showed only a weak response in the eukaryotic bioassays. Storage of the samples for several months at 0 degrees C revealed that the bacterial mutagens present in the most polar fraction were labile; the mutagenicity was almost totally lost after 1 year's storage.

Cyclic GMP efflux from liver slices.

Cyclic GMP efflux from liver slices was studied when the intracellular cyclic GMP levels were elevated by incubation with N-methyl-N'-nitro-N-nitrosoguanidine (0.1 mM) and 3-isobutyl-1-methylxanthine (0.25 mM). A probenecid-sensitive and a probenecid-insensitive efflux system for cyclic GMP was found. It is suggested that the former system operates a carrier, which is saturable, the capacity of which is increased by alkylation with N-ethylmaleimide. The rate of net efflux of cyclic GMP increases 20-fold in the temperature interval 18-37 degrees C. Probenecid (0.5 mM) gives 50% inhibition of this system. The probenecid-insensitive cyclic GMP efflux component probably corresponds to passive diffusion. It appears that efflux may be an important complement to cyclic 3':5'-nucleotide phosphodiesterase activity in reducing intracellular cyclic GMP levels.