Inflammation: the dynamic force of health and disease.

Replacing "happiness" with "inflammation" in Thomas Merton's quotation holds true for the processes that govern our immune response and health. The balance between pro- and anti-inflammatory signals regulates inflammatory responses, leading to either restoration of health or the development and progression of disease, depending on whether it creates equilibrium or dysfunction. This issue of Clinical Pharmacology & Therapeutics highlights emerging research and concepts related to inflammation and its underlying role in chronic disease and variable drug response.

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.

We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTX(ePC)) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3(Luc)) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol, sustained PTX(ePC) therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.

Infrared study of some synthetic phases of malachite (Cu2(OH)2CO3)-hydrozincite (Zn5(OH)6(CO3)2) series.

Synthetic malachite, hydrozincite and five monophasic mixed copper-zinc hydroxycarbonates have been studied by Fourier transform infrared (FTIR) spectroscopy at ambient and liquid nitrogen temperature in the region of 4000-400 cm(-1). The analysis of the spectra reveals that the samples containing up to 20% zinc retain the malachite lattice, thus forming solid solutions. The inclusion of zinc ions in malachite reflects on the positions and intensity of the bands corresponding to the internal modes of the carbonate ion, to the OH librations and to the Me-O interactions. For example, the higher and the lower frequency components of v3 shift to higher and lower frequencies, respectively. The intensity of the bands corresponding to v2 decreases with the zinc content increase. The spectrum of the sample Cu1.31Zn0.69(OH)2CO3 become diffuse and ill-resolved in the region of the Me-O interactions (region below 600 cm(-1)) and the corresponding bands are shifted to lower frequencies due to the weaker Zn-O interactions as compared with those of the copper ions. The internal modes of the carbonate ions in hydrozincite and aurichalcite are assigned and discussed taking into account the site symmetry and factor group symmetry. The OH and OD stretches (matrix-isolated HDO molecules) and the hydrogen bond strengths are interpreted in terms of Me-O interactions (synergetic effect), hydrogen bond angles and different hydrogen bond acceptor strengths of the oxygen atoms from the carbonate ions. It proves that the hydrogen bonds in hydrozincite are stronger as compared with those in malachite, irrespective of both the larger hydrogen bond lengths and the weaker Zn-O interactions in hydrozincite due to the higher hydrogen bond acceptor strength of the non-coordinated oxygen atom and the formation of bifurcated hydrogen bonds.

Conservative treatment of invasive lobular breast cancer.

PURPOSE: To assess the efficacy of breast conserving surgery (BCS), followed by postoperative radiation treatment (RT), chemotherapy and/or hormonotherapy in patients with early invasive lobular breast cancer (ILC). PATIENTS AND METHODS: 48 patients with TNM stages I and II ILC of the breast were treated conservatively by BCS (quadrantectomy) and axillary dissection to levels I and II, followed by RT and adjuvant chemotherapy or hormonal treatment. In patients with pN0 the remaining breast with scar and chest were treated by RT, with a total radiation dose (TRD) of 50 Gy. In cases with pN1 the axilla was included to the described field with TRD 50 Gy. In patients with high risk factors (pT2, tumor necrosis, infiltration of the subcutaneous fat and of lymph and/or blood vessels) the tumor bed was boosted up to a TRD of 60 Gy. The 5 and 10- year cancer-specific and recurrence-free survival were calculated according to the Kaplan-Meyer life-table method. RESULTS: With a median observation period of 6.5 years (range 1.5-11.5 years) 2 (4.1%) patients developed local recurrence and 2 (4.1%) distant metastases. Ten-year cancer- specific and recurrence-free survival are 97% and 90%, respectively. CONCLUSION: The obtained good treatment results proved that the conservative treatment strategy in cases with ILC of the breast is a correct therapeutic choice.

Interferon induction and action in transformed poikilothermic cells.

The production and effect of interferon in the virus-transformed cell line TGk1, originating from kidney cells of Testudo gracea were studied and compared to those in the primary cell culture. West Nile virus and Newcastle disease virus were used as inducers. Interferon production in TGk1 cells began 6 hr later than in the primary cell culture and reached the maximum 64 IU, 18 hr after virus inoculation. In the primary culture, interferon production increased till the 48th hr reaching a fourfold level (256 IU). A significant reduction of the antiviral effect of interferon against vesicular stomatitis virus but not against vaccinia virus was observed in the transformed cells. The decreased interferon production and effect in TGk1 cells is regarded as a consequence of the disturbance of the interferon regulatory mechanism taking place as a result of the virus-induced transformation.