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Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study.

epirubicin, fluorouracil, adjuvant, cyclophosphamide, radiotherapy in breast cancer, study, longitudinal, longitudinal study, adjuvant chemotherapy, immune, effects, cancer, chemotherapy, radiotherapy, Systemic immune effects, immune effects, Systemic, breast cancer No Comments

breast cancer 

Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska University Hospital Solna, Stockholm, Sweden.

Immunotherapy is being increasingly utilized for adjuvant treatment for breast cancer (BC). We have previously described immune functions during primary therapy for BC. The present study describes immune recovery patterns during long-term, unmaintained follow-up after completion of adjuvant therapy.A group of patients with primary BC had been treated with adjuvant radio-chemotherapy (RT + CT) 5-fluorouracil, epirubicin and cyclophosphamide (FEC) (n = 21) and another group with radiotherapy (RT) (n = 20) alone. Immunological testing of NK and T-cell functions was performed initially at the end of adjuvant treatment and repeated after 2, 6 and 12 months. NK cell cytotoxicity was significantly higher (P < 0.05) at all time-points in patients than in age-matched controls and did not differ between the two treatments groups during one year observation. In contrast, lower numbers of CD4 T-cells and lower expression of CD28 on T-cells was observed particularly in RT + CT patients and did not normalize during the observation period. The numbers of T(reg) cells (CD4(+)CD25(high)) were low in the RT + CT group during follow-up, as well as expression of TCRxi, Zap70, p56(lck), P59(fyn) and PI3 k in CD4(+) cells. In contrast, expression of intracellular cytokines (IFN-gamma, IL-2, IL-4) in CD4 and CD8 T cells were significantly higher in RT + CT patients than in the RT group and the difference increased during follow-up. In conclusion, NK-cell cytotoxicity increased during unmaintained long-term follow-up whereas CD4 and regulatory T cells as well as signal transduction molecules remained low following adjuvant radio-chemotherapy.

Use of instrumental variables in the presence of heterogeneity and self-selection: an application to treatments of breast cancer patients.

estimating, health economics, Instrumental variable, effects, treatment No Comments

Instrumental variable (IV) methods are widely used in the health economics literature to adjust for hidden selection biases in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the proper use of IVs if treatment effects are heterogeneous across subjects and individuals select treatments based on expected idiosyncratic gains or losses from treatments. In this paper we compare conventional IV analysis with alternative approaches that use IVs to estimate treatment effects in models with response heterogeneity and self-selection.
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Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75.

epigallocatechin, gallate, C75, effects, inhibitory, metabolism, breast cancer cells, differential, Fatty acid No Comments

 

Endogenous fatty acid metabolism is crucial to maintain the cancer cell malignant phenotype. Lipogenesis is regulated by the enzyme fatty acid synthase (FASN); and breakdown of fatty acids is regulated by carnitine palmitoyltransferase-1 (CPT-I). FASN is highly expressed in breast cancer and most common human carcinomas. Several compounds can inhibit FASN, although the degree of specificity of this inhibition has not been addressed. We have tested the effects of C75 and (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism pathways, cellular proliferation, induction of apoptosis and cell signalling in human breast cancer cells.

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