Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model.

Female breast cancer is the most deadly cancer in women worldwide. The triple-negative breast cancer subtype therapies, due to the lack of specific drug targets, are still based on systemic chemotherapy with doxorubicin, which is burdened with severe adverse effects. To enhance therapeutic success and protect against systemic toxicity, drug carriers or combination therapy are being developed. Thus, an innovative liposomal formulation containing doxorubicin and the main nutraceutical, sulforaphane, has been developed. The anticancer efficacy and safety of the proposed liposomal formulation was evaluated in vivo, in a 4T1 mouse model of triple-negative breast cancer, and the mechanism of action was determined in vitro, using triple-negative breast cancer MDA-MB-231 and non-tumorigenic breast MCF-10A cell line. The elaborated drug carriers were shown to efficiently deliver both compounds into the cancer cell and direct doxorubicin to the cell nucleus. Incorporation of sulforaphane resulted in a twofold inhibition of tumor growth and the potential of up to a fourfold reduction in doxorubicin concentration due to the synergistic interaction between the two compounds. Sulforaphane was shown to increase the accumulation of doxorubicin in the nuclei of cancer cells, accompanied by inhibition of mitosis, without affecting the reactive oxygen species status of the cell. In normal cells, an antagonistic effect resulting in less cytotoxicity was observed. In vivo results showed that sulforaphane incorporation yielded not only cardioprotective, but also nephro- and hepatoprotective effects. The results of the research revealed the prospects of applying sulforaphane as a component of liposomal doxorubicin in triple-negative breast cancer chemotherapy.

Psychometric properties of the Polish version of the Self-Pluralism Scale (SPS).

BACKGROUND: The Self-Pluralism Scale (SPS) measures the declared degree of self-pluralism, visible already in William James's works. Self-pluralism refers to the degree to which one perceives oneself as typically feeling, behaving, and being different, in different situations, and at different times. The purpose of the current study was to evaluate the psychometric properties of the Polish version of the SPS. PARTICIPANTS AND PROCEDURE: A total of 1747 participants (67% were women) between the ages of 15 and 70 years completed the SPS along with measures of self-concept inconsistency, self-concept differentiation, dissociative experiences, internal dialogical activity, personality, and social desirability. RESULTS: Internal reliability and test-retest reliability were high. The full version has too low indices of fit whereas the brief, 10-item version fits the data well. As indicators of the convergent validity, a positive correlation of SPS with self-concept inconsistency, self-concept differentiation, dissociative experiences, internal dialogical activity and neuroticism and a negative correlation with agreeableness and social desirability were found. CONCLUSIONS: The results suggest that the brief, 10-item version is more valid than the full, 30-item version. The tool may be used for scientific research concerning self-pluralism. After collecting data from a sample that would allow norms to be constructed, the tool may also be useful for individual diagnosis.

Interactions between drugs and sulforaphane modulate the drug metabolism enzymatic system.

BACKGROUND: Sulforaphane (SFN) is a potent chemopreventive agent, which is widely consumed in diet or as a diet supplement. It modulates the enzymes of II and III metabolism phase. In this paper, the influence of SFN and three commonly consumed drugs: furosemide, verapamil and ketoprofen on II and III metabolisms phase enzymes was studied. We have also investigated if the interactions between SFN and the drugs occur resulting in enzymatic system disturbances. METHODS: The Caco-2 cells were incubated with SFN and drugs separately or in a mixture simultaneously or subsequently. The impact of the compounds on the cell viability and NADPH:quinine reductase (QR) activity was determined. The expression of glutathione-S-transferase (GST) isoenzymes GSTA3, GSTM1, P-glycoprotein (PgP) and multidrug resistance protein 1 (MRP1) genes was measured by qPCR method. Since these enzymes are regulated by Nrf2 pathway, the localization of Nrf2 (Nuclear erythroid 2-related factor) after exposure to the mixtures of SFN and the drugs was evaluated by confocal microscopy. RESULTS: SFN was shown to interact antagonistically with the studied drugs. At most cases an increase in enzymatic activity and expression was observed. The most significant changes were observed in case of enzymes regulated by Nrf2: QR, GSTA1 and GSTA3 and also MRP1. PgP was shown to be not altered by the studied compounds. COCNCLUSION: The interaction between SFN and furosemide, verapamil and ketoprofen modify the activity of enzymatic system involved in drug metabolism and transport. This may lead to drug effectiveness alteration and also to multidrug resistance (MDR) development.

[Use and abuse of alcohol and other psychoactive substances among Polish university students]. / Uzywanie i naduzywanie alkoholu i innych substancji psychoaktywnych przez polskich studentów.

The results of country-wide research on alcohol and psychoactive substances use among Polish students are presented. The survey was carried out in the year 2000 and included 9446 students from 8 major academic centres in Poland. Negative events linked with the use of alcohol and drugs were discovered - 40% of students (42% of men and 37% of women) during the last two weeks exceeded the limit of dangerous drinking. Large range of harmful consequences of binge drinking has been found - one in three men and one in four women committed acts under the influence of alcohol, which they regretted after. One in four men under influence of alcohol was involved in aggressive fights with peers and one in six has had serious trouble with studying and bad assessments. The scope of drug use was much smaller but also alarming. During the last 30 days 7% of the studied population reported use of marijuana and 1.5% amphetamine. Abuse of alcohol was correlated with use of drugs. This creates a serious risk of cross addiction and shows an important role of alcohol drinking as a gateway to drug use.