Unusual Enhancement of Doxorubicin Activity on Co-Delivery with Polyhedral Oligomeric Silsesquioxane (POSS)

Polyhedral oligomeric silsesquioxane (POSS), bearing eight 3-chloroammoniumpropyl substituents, was studied as a potential nanocarrier in co-delivery systems with doxorubicin (DOX). The toxicity of doxorubicin and POSS:DOX complexes at four different molar ratios (1:1; 1:2, 1:4, 1:8) towards microvascular endothelial cells (HMEC-1), breast cancer cells (MCF-7), and human cervical cancer endothelial cells (HeLa) was determined. The rate of penetration of the components into the cells, their cellular localization and the hydrodynamic diameter of the complexes was also determined. A cytotoxicity profile of POSS:DOX complexes indicated that the POSS:DOX system at the molar ratio of 1:8 was more effective than free DOX. Confocal images showed that DOX co-delivery with POSS allowed for more effective penetration of doxorubicin through the cell membrane. Taking all the results into account, it can be claimed that the polyhedral oligomeric silsesquioxane (T8-POSS) is a promising, complex nanocarrier for doxorubicin delivery

Molecular mechanisms of antitumor activity of PAMAM dendrimer conjugates with anticancer drugs and a monoclonal antibody

Taxanes are considered fundamental drugs in the treatment of breast cancer, but despite the similarities, docetaxel (doc) and paclitaxel (ptx) work differently. For this reason, it is interesting to identify mechanisms of antitumor activity of PAMAM dendrimer conjugates that carry docetaxel or paclitaxel and monoclonal antibody trastuzumab, specifically targeted to cells which overexpressed HER-2. For this purpose, the impact on the level of reactive oxygen species, the mitochondrial membrane potential, cell cycle distribution and the activity of caspases-3/7, -8 and -9 of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined and compared with free docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines. Moreover, apoptosis and necrosis were studied using flow cytometry and confocal microscopy, respectively. Our studies show the complexity of the potential mechanism of cytotoxic action of PAMAM-drug-trastuzumab conjugates that should be sought as a resultant of oxidative stress, mitochondrial activation of the caspase cascade and the HER-2 receptor blockade

Neonatal survival and kidney function after prenatal interventions for obstructive uropathies

Objectives: Prenatal interventions in LUTO (lower urinary tract obstruction) usually are still question of a debate between gynaecologist and paediatric nephrologist. We aimed the study to assess the early survival rate and renal outcome in LUTO foetuses. Material and methods: The study was a prospective data analysis of 39 foetuses from singleton pregnancies. All pregnant women with LUTO in the foetus were qualified for VAS based on a local practice. The mean time of first urine analysis ranged between 13–30 weeks of pregnancy. Primary end-point analysis included live birth, 28d-survival, pulmonary and renal function assessment in neonatal period. Results: From initial number of 39, six patients miscarried before the procedure was performed. Overall, 33 VAS were performer at the mean 21 week of pregnancy (range 14–30 weeks). 25/39 foetuses survived until delivery. Three neonates died in first 3 days of life. In the first month 3 children required peritoneal dialysis, but at 28 day all children were dialysis-free. Overall survival rate at 28 day was 56%. Renal function preservation of the initial group (39) turned out to be low — 18% (7/39). Conclusions: Our study showed average survival curves and complications. LUTO in the foetus had mostly unfavourable outcome in the neonatal period. The prenatal intervention did not increase it significantly and did not guarantee the preservation of normal kidney function

Music therapy in supportive cancer care

The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients—interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life

Molecular Mechanisms of Antitumor Activity of PAMAM Dendrimer Conjugates with Anticancer Drugs and a Monoclonal Antibody

Taxanes are considered fundamental drugs in the treatment of breast cancer, but despite the similarities, docetaxel (doc) and paclitaxel (ptx) work differently. For this reason, it is interesting to identify mechanisms of antitumor activity of PAMAM dendrimer conjugates that carry docetaxel or paclitaxel and monoclonal antibody trastuzumab, specifically targeted to cells which overexpressed HER-2. For this purpose, the impact on the level of reactive oxygen species, the mitochondrial membrane potential, cell cycle distribution and the activity of caspases-3/7, -8 and -9 of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined and compared with free docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines. Moreover, apoptosis and necrosis were studied using flow cytometry and confocal microscopy, respectively. Our studies show the complexity of the potential mechanism of cytotoxic action of PAMAM-drug-trastuzumab conjugates that should be sought as a resultant of oxidative stress, mitochondrial activation of the caspase cascade and the HER-2 receptor blockade

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

OBJECTIVE: Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor in development for treatment of several immunological diseases. Efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks. METHODS: This placebo-controlled, dose-ranging, phase IIb study randomized participants to brepocitinib 10 mg once daily (QD), 30 mg QD, 60 mg QD, or placebo, advancing to brepocitinib 30 or 60 mg QD at week 16. The primary endpoint was American College of Rheumatology (ACR)20 response rate at week 16. Secondary endpoints included response rates of ACR50/70, 75% and 90% improvement in Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) at weeks 16 and 52. Adverse events (AEs) were monitored throughout. RESULTS: Overall, 218 participants were randomized and treated. At week 16, brepocitinib 30 and 60 mg QD groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus placebo (43.3%) and significantly higher ACR50/70, PASI75/90, and MDA response rates. Response rates were maintained or improved through week 52. AEs were mostly mild/moderate; serious AEs (15) in 12 (5.5%) participants included infections in 6 (2.8%) in brepocitinib 30 and 60 mg QD groups. No major adverse cardiovascular events or deaths occurred. CONCLUSION: Brepocitinib 30 and 60 mg QD were superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study with a safety profile consistent with other brepocitinib clinical trials

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease

Objective To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis