Determinants of CPT-11 and SN-38 activities in human lung cancer cells

Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11. The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase I protein expression were investigated in five human small-cell lung cancer (SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines. Antiproliferative activity, expressed as IC50 values, was determined using the MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines (P = 0.0036), whereas no significant difference between histological types was observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and significantly higher CE activity was observed in SCLC compared with NSCLC cell lines (P = 0.025). Western blotting experiments showed topoisomerase I protein expressions within a factor of 2, and a granular nuclear staining was detectable in all cell lines by immunocytochemistry of cytospins. No correlation was observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular and medium concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the SCLC cell line, and this was associated with an increase in cellular uptake of CPT-11 compared with the medium, and an increased intracellular formation of SN-38. In conclusion, CE activity appears to be associated with higher sensitivity to CPT-11 in human lung cancer cell lines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The assessment of CE activity in clinical material of lung cancer patients undergoing treatment with CPT-11 may be warranted. However, other mechanisms may influence sensitivity to CPT-11, possibly including drug transport.     

Developmental stages in experimental liver metastases: relation to invasiveness

We have previously reported that an invasive morphotype can be evoked in a rat colon carcinoma by transplanting it into pre-induced subcutaneous granulation tissue. We have now studied the interaction of the same tumor with liver tissue, which is extremely poor in connective tissue in comparison with the subcutaneous site. Tumor cells were injected into the portal system and the resulting experimental liver metastases were examined by electron microscopy and immunohistochemistry. Early metastases consisted of well-differentiated acini, fully surrounded by connective tissue that was derived from the periportal stroma. In a later stage, this connective tissue was overgrown by tumor cells and, almost immediately, acinar differentiation was lost. Most metastases eventually reached the liver capsule, which reacted by forming a layer of granulation tissue. Only in this layer, we observed invasion by thin tumor cell strands, which were often intimately associated with fibroblasts or with blood capillaries. The tumor cells remained smooth and rounded during this process. After fully penetrating the granulation tissue, the tumor cell strands reached the liver surface, where they formed poorly structured papillary masses that were nearly devoid of stroma. Our observations indicate that, even in a relatively homogeneous organ like the liver, the tumor-host interaction is highly complex and dynamic. They also confirm the notion that granulation tissue stimulates tumor invasiveness. Finally, they show that tumor cells can actively invade host tissues without exhibiting a "fibroblastic" morphology.     

In-situ transmission measurements as process control for thin-film silicon solar cells

In this work, in-situ transmission measurements using plasma as light source are presented for the determination of growth rate and crystallinity during silicon thin-film growth. The intensity of distinct plasma emission lines was measured at the backside of the transparent substrates on which silicon films, ranging from amorphous to microcrystalline, were deposited. Using this configuration, the growth rate of thin-films was determined with high accuracy. In addition, we show that the crystallinity of the films can be monitored in the most critical range (between 40% and 80%) for microcrystalline silicon solar cells by evaluating the intensity ratio of two transmitted wavelengths in-situ. The gradual change in the absorption behaviour of the films during the phase transition is reflected by this ratio of two wavelengths as demonstrated by the good correlation with the crystallinity fraction determined by ex-situ Raman spectroscopy. This approach of in-situ transmission spectroscopy provides an easy-to-implement monitoring and control system for the industrial deposition of thin-film silicon solar cells, as critical material properties can be determined real-time during the deposition process even on rough substrates that are optimized for light trapping in solar cells.     

Early intervention, untreated psychosis and the course of early schizophrenia

BACKGROUND: Studies have proved that early intervention can delay psychotic relapses, and prevent psychosocial deterioration in people with schizophrenia and related disorders. METHOD: Our study with young people with recent onset schizophrenia has shown that an intensive intervention programme had a beneficial effect on the occurrence of psychotic relapse and the course of psychotic syndromes. This effect lasted until the end of the 15-month intervention. No significant effect of the two different intervention conditions became apparent. RESULTS: The results of a follow-up study showed that this beneficial effect did not last. Fifteen per cent of the people had a psychotic relapse during the intervention, whereas 64% relapsed during follow-up. CONCLUSIONS: These results show that referral to other mental health agencies after intervention is not sufficient and that more support is required to continue disease management, medication compliance and stress management.     

Long-Term Memory Deficits in Schizophrenia: Primary or Secondary Dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-performance composites based on all-aromatic liquid crystal thermosets

In this study, a new high-performance liquid crystal ester-based thermoset for composite applications was investigated. All-aromatic liquid crystalline thermosets (LCTs) are a promising class of polymers that offer a unique combination of properties such as solvent resistivity, high modulus, high strength, low coefficient of thermal expansion and high after cure glass-transition temperatures (T_g ? 150 °C). Fully cured LCTs offer superior thermo-mechanical properties over high-performance thermoplastic polymers such as PPS, PEEK and PEI. For this study we used a 9000 g mol⁻¹ ester-based LCT based on cheap and readily available monomers, i.e. 4-hydroxybenzoic acid (H), isophthalic acid (I) and hydroquinone (Q), abbreviated by us as HIQ-9. Composite panels prepared from T300 carbon fiber (5-harness satin weave) showed in-plane shear strength of 154 MPa and an in-plane shear modulus of 3.7 GPa. The tensile strength and modulus were measured to be 696 MPa and 57 GPa, respectively. A post-mortem inspection showed that the interfacial strength was excellent and no delamination was observed in the test specimen. Preliminary results show that LCT-based composites exhibit a better combination of (thermo) mechanical properties over PPS and PEI-based composites.     

Flexible all‐aromatic polyesterimide films with high glass transition temperatures

A series all‐aromatic poly(esterimide)s with different molar ratios of N‐(3′‐hydroxyphenyl)‐trimellitimide (IM) and 4‐hydroxybenzoic acid (HBA) (IM/HBA = 0.3/0.7 and 0.7/0.3) was prepared with the aim to design flexible high T_g films. Melt‐pressed films, either from high molecular weight polymer or cured phenylethynyl precursor oligomers, exhibit T_gs in the range of 200 °C to 242 °C and are brittle. After a thermal stretching procedure, the films became remarkably flexible and very easy to handle. In addition, the thermally stretched 3‐IM/7‐HBA and 7‐IM/3‐HBA films show tensile strengths of 108 MPa and 169 MPa, respectively. Thermal treatment increased the T_g of 3‐IM/7‐HBA from 205 °C to 248 °C, whereas the T_g of 7‐IM/3‐HBA increased from 230 °C to 260 °C. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 133, 44774.     

Uniaxial and biaxial nematic liquid crystals

The unusual exhibition of a biaxial nematic phase in nonlinear thermotropic mesogens derived from the 2,5-oxadiazole biphenol (ODBP) core is placed in a general context; the uniaxial nematic phase of the prototypical rod-like mesogen para-quinquephenyl does not follow the classical mean-field behaviour of nematics, thus questioning the utility of such theories for quantitative predictions about biaxial nematics. The nuclear magnetic resonance spectra of labelled probe molecules dissolved in ODBP biaxial nematic phases suggest that a second critical rotation frequency, related to the differences in the transverse diamagnetic susceptibilities of the biaxial nematic, must be exceeded in order to create an aligned two-dimensional powder sample. Efforts to find higher viscosity and lower temperature biaxial nematics (with lower critical rotation rates) to confirm the above conjecture are described. Several chemical modifications of the ODBP mesogenic core are presented.     

Thermotropic liquid crystalline polymers as protective coatings for aerospace

Liquid crystalline polymers (LCPs) have potential as multifunctional, environmentally friendly coatings for aerospace, overcoming the disadvantages of current materials. Their use, however, has been hindered mainly by their poor adhesion strength. The present work studies novel liquid crystalline thermosetting polymers (LCTs), which can overcome the disadvantages of commercial LCPs for protective coatings in aerospace applications. Phenylethynyl terminated liquid crystalline oligomers based on 4-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) were synthesized and melt-pressed on grit-blasted aluminum to obtain 25 μm and 80 μm thick coatings. The presence of coating defects and curing kinetics were investigated, and the adhesion, mechanical properties and environmental resistance were compared with a commercial LCP reference material (Vectra^®). The LCTs showed highly improved adhesion; moreover, fully cured LCTs are harder and stiffer than commercial LCPs, which are expected to increase their wear and impact resistance. The coatings showed no swelling, peeling, or blistering after 500 h of full immersion in fluids such as jet fuel and turbine oil; furthermore, LCTs resisted 1000 h in corrosive fog (salt-spray) and hot moisture. Exposed samples retained their hardness, modulus, and pull-off strength, evidencing the outstanding chemical resistance of these LCTs. Our findings showed the potential of LCTs as protective and wear resistant coatings, particularly in the aggressive environments of aerospace applications. However, results suggest that exposed coating/substrate interfaces constitute paths for environmental attack. Further research aims at elucidating the possible mechanisms.