NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy

Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions

Replacement of the terminal methyl group in a moth sex pheromone component by a halogen atom: Hydrophobicity and size effects on electrophysiological single-cell activities

Analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth, Agrotis segetum, with a chloro, bromo, or iodo substituent in place of the terminal methyl group have been synthesized and tested by electrophysiological single-sensillum recordings. The electrophysiological results have been interpreted in terms of substituent size and hydrophobicity. Interaction energies based on receptor interaction models have been calculated using the molecular mechanics [MM2(85)] method. The results support our previously suggested receptor interaction model in which the terminal alkyl chain interact with a complementary hydrophobic receptor "pocket" with very limited flexibility

Conformationally constrained analogues of (Z)-5-decenyl acetate, a pheromone component of Agrotis segetum

Conformationally constrained analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesized and tested by using electrophysiological single-cell recordings. In the constrained analogues the terminal alkyl chain in 1 has been incorporated in a six-membered (3 and 1) or five-membered (6) ring system. These cyclic compounds are also conformationally constrained analogues of the previously deduced bioactive conformations of the corresponding chain-elongated analogues 2 and 5. The electrophysiological activities of the constrained analogues are found to be significantly lower than that of the natural pheromone component 1, most probably due to steric repulsive interactions between the analogue and the receptor, and also lower than the activities of the corresponding chain-elongated analogues of 1. It is concluded that the flexibility of the terminal chains in 2 and 5 is essential for the possibility of the receptor to accommodate these parts of the chain-elongated analogues in their bioactive conformations. Copyright (C) 1996 Elsevier Science Lt

Introduction of methyl groups to acetate substituted chain of (Z)-5-decenyl acetate, a pheromone component of turnip moth,agrotis segetum: synthesis, single-sensillum recordings, and structure-activity relationships

Methyl-substituted analogs of (Z)-5-decenyl acetate, a phermone component of the turnip moth, Agrotis segetum, have been synthesized and studied by electrophysiological single-sensillum recordings and molecular mechanics calculations [MM2(85)]. The analogs are monomethyl substituted in the 2, 3, 4, and 5 positions and geminally dimethyl substituted in the 2, 3, and 4 positions. The methyl groups have been employed as space probes to study the degree of steric complementarity between the acetate-substituted alkyl chain of the pheromone component and its receptor. The electrophysiological activities, interpreted in terms of a receptor interaction model, indicate significant steric repulsive interactions between the introduced methyl groups and the receptor. This implies a high degree of complementarity between the acetate-substituted alkyl chain of the natural pheromone component and its receptor

Alkyl substitution in terminal chain of (Z)-5-decenyl acetate, a pheromone component of turnip moth, Agrotis segetum. Synthesis, single-sensillum recordings, and structure-activity relationships

Structure-activity relationships for 6-, 7-, 8-, and 9-alkyl substituted analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth, Agrotis segetum, have been studied by electrophysiological single-sensillum recordings, and interpreted in terms of a receptor-interaction model. The compounds were prepared by alkenyl cuprate reactions with alpha,beta-unsaturated carbonyl derivatives or alkyl halides. The electrophysiological results indicate steric repulsive interactions between the alkyl groups and the receptor in all the positions studied. This demonstrates a high complementarity between the receptor and the terminal alkyl chain