Patients in the TAU group will receive the treatment routinely offered to patients undergoing RT for breast cancer.

Patients in the PSY group will participate to a short-term group psychotherapy with elements of music therapy; meetings will be 1 / week, for a total of 6 weeks. Beginning of psychotherapy intervention will be 1-2 weeks after recruitment at T0 and will therefore cover the entire duration of the RT cycle.

Breast Cancer

Depression, Anxiety

Oxidative Stress

Group psychotherapy with music intervention

Music therapy intervention

Department of Translational Medicine, Università del Piemonte Orientale

Oxidative Stress, Anxiety and Depression in Breast Cancer Patients: Impact of Music Therapy

Analisi Dei Marcatori di Stress Ossidativo in Pazienti Affetti da Tumore Della Mammella, Sottoposte a Radioterapia Postoperatoria e Psicoterapia Con Elementi di Musicoterapia

Anxiety is assessed with the State-Trait Anxiety Inventory 1 and 2 (STAI Y1, STAI Y2), a 40-item self-administered test for the assessment of state and trait anxiety. Each item is rated 1 to 4 (1= not at all, 4= severe); no specific cut-off scores exist. The highest the score, the greater is anxiety.

Depression is assessed with the Montgomery-Asberg Depression Rating Scale (MADRS and with the Beck Depression Inventory (BDI). The MADRS is a 10-item clinician-rated scale for depressive symptoms detection and severity assessment. Each item is rated on a six-point scale, hence 60 is the maximum total score indicating the maximum severity of depressive symptoms. A score <6 points stands for no depression (normal), 7-19 mild depression, 20-34 moderate depression, ≥ 35 severe depression. The BDI is a 21-item self-administered test for the evaluation of subjective depressive feelings or symptoms. It is rated on a 4-points scale (from 0 to 3 according to severity), with the following cutoff values: 0-9 minimal depression, 10-18 mild depression, 19-29 moderate depression, 30-63 severe depression.

GSH measurement was performed through the Glutathione Assay Kit (Cayman Chemical, Ann Arbor, MI, USA). For the experiments, each plasma sample was deproteinated and centrifuged at 2000 g for 2 min. Fifty μl of the samples was transferred to a 96‐well plate where GSH was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), at excitation/emission wavelengths of 405-414 nm. To ensure accurate GSH quantification (expressed as µM), a reference curve with the GSH Standard was prepared (range of known GSH concentration: 0-16 μM). As regards the performance of the assay, variation coefficient of 3.6% for inter-assay and 1.6% for intra-assay is reported.

TBARS were determined as malonyldialdeide (MDA) release. MDA measurement was performed by using the TBARS assay Kit (Cayman Chemical). For the experiments, 100 µl of each plasma sample was added to 100 µl of sodium dodecyl sulfate (SDS) solution and 2 ml of the Color Reagent. After centrifugation, 150 μl of each sample was transferred to a 96‐well plate where MDA was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), at excitation/emission wavelengths of 530-540 nm. In order to quantify the correct values of TBARS (expressed as µM MDA), a reference standard curve was prepared (range of known TBARS concentration: 0-50 μM). As regards the performance of the assay, intra-coefficient of variation of 5.5% and an inter-coefficient variation of 5.9% is reported.

Resilience is assessed with the Resilience Scale for Adults (RSA). This is a 33-item self-administered scale evaluating intra- or inter-relational stress preventing factors (positive self-perception, positive future perception, social competence, structured style, family cohesion and social resources). The higher is the total score, the greater is the subject's resilience.

Quality of life is assessed with the Short Form-36 (SF-36), a self-administered test assessing health-related quality of life, both from a somatic and psychological standpoint. It assesses several sub-areas: physical activity, role and physical health, physical pain, general health, vitality, social activities, role and emotional state, mental health and health change. Results are expressed in age- calculated percentiles.

IL-6 measurement was performed by using the Human IL-6 ELISA kit (Invitrogen Carlsbad, California, USA). For the experiments, 50 μl of each plasma sample and 50 μl of Assay Buffer 1X were added to each well, with 50 μl of Biotin-Conjugate and incubated at room temperature (RT) on microplate shaker for 2 h. After addition of 400 μl Wash Buffer, 100 μl Streptavidin-HRP and 100 μl Substrate Solution, each well was incubated for 10 min at RT in the dark. The enzyme reaction was stopped by adding 100 μl Stop Solution, and IL-6 was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), using a wavelength of 450 nm. In order to quantify the correct value of IL-6 in each sample (expressed as pg/ml), a reference standard curve was prepared (range of IL-6 standard concentration:0-20 pg/mL). As regards the performance of the assay, intra-coefficient of variation of 8.5% and an inter-coefficient variation of 9.8% is reported. The sensitivity of the test is < 1 pg/ml.

TNFα measurement was performed with the Human TNF alpha ELISA kit (Invitrogen, Carlsbad, California, USA). For the experiments, 50 μl of each plasma sample and 50 μl of Sample Diluent were added to each well, with 50 μl of Biotin-Conjugate and incubated at RT on microplate shaker for 2 h. After addition of 400 μl Wash Buffer, 100 μl Streptavidin-HRP and 100 μl Substrate Solution, each well was incubated for 10 min at RT in the dark. The enzyme reaction was stopped by adding 100 μl of Stop Solution and each well was read immediately. TNFα was detected through a spectrophotometer (VICTOR™ X Multilabel Plate Reader), using a wavelength of 620 nm. To quantify the correct value of in each sample, a reference standard curve was prepared (range of TNFα standard concentration: 0-100 pg/mL). As regards the performance of the assay, intra-coefficient of variation of 3.4% and inter-coefficient variation of 5.2% is reported. The sensitivity of the test is 0.13 pg/ml.

HPLC analysis of retinol, α and γ -tocopherol, lycopene and β carotene were carried out on Agilent 1200 series HPLC.
200 ml of each plasma sample was mixed with 300µl of water and 500 µl of ice-cold absolute ethanol and immediately vortexed for 10 s. Two millilitres of ice-cold hexane was added. The mixture was immediately vortexed for 2 minutes and then centrifuged at 3000 g for 1 min and 1 ml of the upper (organic) layer was transferred in a vial, evaporated to dryness under a nitrogen stream and reconstituted with 100 ml of a mixture of acetonitrile/dichloromethane/methanol for HPLC analysis.
Twenty microlitres of this mixture were then injected and the antioxidants were eluted with a mobile phase containing acetonitrile/dichloromethane/methanol, glacial acetic acid (1 g /l) at a constant flow of 1.8 ml/min.
Detection of lipid soluble antioxidants was performed at specific wavelength: retinol (326 nm), γ- and α-tocopherol (292nm), lycopene and β-carotene (460nm).

Colesterol and high sensitivity C-reactive Protein (CRP) were analyzed on ADVIA® 1800 Clinical Chemistry Analyzer (Siemens Healthcare Diagnostics), by automated methods and certified kits.
Colesterol (range:0 - 200 mg/dL) High sensitivity C-reactive Protein (range:0 - 1 mg/dL)

Marco Krengli

Full Professor

Università degli Studi del Piemonte Orientale "Amedeo Avogadro"

The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive 1 dose of 1 g MaxSimil® fish oil + 200 mg CoQ10. The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.

The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive 1 dose of 1 g rice bran oil + 200 mg CoQ10. The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.

Healthy

The intervention is a randomized double blind cross over design testing the pharmacokinetics of 1) CoQ10 combined with MaxSimil fish oil as a carrier, 2) CoQ10 combined with rice bran oil as a carrier, and 3) CoQ10 as a powder form.
Treatments are randomly assigned on days 1, 8 and 15 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 10, 12, 24 and 48 hours. Each participant will perform all three treatments, with a minimum of 7 days between treatments. A questionnaire will document the side effects felt by participants.

MaxSimil® fish oil + CoQ10

Rice bran oil + CoQ10

CoQ10 as powder form

Centre de Recherche sur le Vieillissement

Pharmacokinetic Study on Three Formulations of Coenzyme Q10 With Different Carriers

Plasma CoQ10 levels will be measured by high-performance liquid chromatography (HPLC), each sample being performed randomly blindly. After HPLC analyzes, area under the curve (AUC) 0-48 hours will be calculated, as the first parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

Plasma CoQ10 levels will be measured by high-performance liquid chromatography (HPLC), each sample being performed randomly blindly. After HPLC analyzes, AUC 0-6 hours (absorption study) will be calculated, as the second parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

Plasma CoQ10 levels will be measured by high-performance liquid chromatography (HPLC), each sample being performed randomly blindly. After HPLC analyzes, maximum concentration will be calculated, as the third parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

Plasma CoQ10 levels will be measured by high-performance liquid chromatography (HPLC), each sample being performed randomly blindly. After HPLC analyzes, time when the maximum concentration is reached will be calculated, as the fourth parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

Mélanie Plourde

Principal investigator

Double-blind controlled-randomized pharmacokinetic (PK) study with crossover design (15 men and 15 women), with a minimum of 6 days between treatments

Neither the participant nor the research nurse will know the administration order of the different treatments administered. All plasma samples collected during the research project will be anonymized i.e. it will not be possible to identify the participant by his name since a number will be assigned to him. The code key linking the participant's name to his number will be stored, with access restricted to those designated by the principal investigator. The data file is also protected by a password.

tocopherol/fatigue

Oxidative Stress, Anxiety and Depression in Breast Cancer Patients: Impact of Music Therapy

Pharmacokinetic Study on Three Formulations of Coenzyme Q10 With Different Carriers

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