AlphaB-crystallin and breast cancer Caporossi, Daniela; Parisi, Attilio; Fantini, Cristina ...
Cell stress & chaperones,
01/2021, Letnik:
26, Številka:
1
Journal Article
Recenzirano
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AlphaB-crystallin (HSPB5) is one of the most prominent and well-studied members of the small heat shock protein (sHsp) family. To date, it is known that this protein modulates significant cellular ...processes and therefore, it is not surprising that its deregulation is involved in various human pathologies, including cancer diseases. Despite the pathogenic significance of HSPB5 in cancer and its regulatory mechanism related to aggressiveness is poorly understood, several reports describe the association of breast carcinoma progression with HSPB5, whose expression is also considered an independent predictor of breast cancer metastasis to the brain. Indeed, numerous authors indicate HSPB5 as a new valuable biomarker for clinicopathological parameters and poor prognosis in breast cancer. Considering the cytoprotective, anti-apoptotic, pro-angiogenic, and pro-metastatic properties of the sHsps, it is not surprising that they are considered as promising targets for anticancer treatment, even though, at present, a deeper understanding of their mode of action is needed to allow the development of precise therapeutic interventions. Data on the direct inhibition of different sHsps demonstrate promising results in cancer pathologies; however, specific strategies against HSPB5 have not been considered. This review highlights the most relevant findings on HSPB5 and its role in breast cancer, as well as the possible strategies in using HSPB5 inhibition for therapeutic purposes.
The increase in breast cancer (BC) survival has determined a growing survivor population that seems to develop several comorbidities and, specifically, treatment-induced cardiovascular disease (CVD), ...especially those patients treated with anthracyclines. Indeed, it is known that these compounds act through the induction of supraphysiological production of reactive oxygen species (ROS), which appear to be central mediators of numerous direct and indirect cardiac adverse consequences. Evidence suggests that physical exercise (PE) practised before, during or after BC treatments could represent a viable non-pharmacological strategy as it increases heart tolerance against many cardiotoxic agents, and therefore improves several functional, subclinical, and clinical parameters. At molecular level, the cardioprotective effects are mainly associated with an exercise-induced increase of stress response proteins (HSP60 and HSP70) and antioxidant (SOD activity, GSH), as well as a decrease in lipid peroxidation, and pro-apoptotic proteins such as Bax, Bax-to-Bcl-2 ratio. Moreover, this protection can potentially be explained by a preservation of myosin heavy chain (MHC) isoform distribution. Despite this knowledge, it is not clear which type of exercise should be suggested in BC patient undergoing anthracycline treatment. This highlights the lack of special guidelines on how affected patients should be managed more efficiently. This review offers a general framework for the role of anthracyclines in the physio-pathological mechanisms of cardiotoxicity and the potential protective role of PE. Finally, potential exercise-based strategies are discussed on the basis of scientific findings.
The international literature emphasizes the importance of physical activity (PA) in the first steps after cancer surgery. The regular practice of physical exercise causes positive adaptations on ...several functional capacities, with positive consequences on patients' quality of life. This project aims to evaluate the effect of a post-operative training protocol, structured by taking into account both cancer-related issues and the presence of comorbidities, on functional capacities and quality of life of breast cancer survivors. Therefore, it was necessary to create a synergy between oncologists (referring physicians), sport medicine physicians (risk stratification and exercise prescription) and kinesiologists (trainers). Thirty-five post-surgery BC patients decided on a voluntary basis to attend an online Adapted PA (APA) protocol for 4 months, twice a week (APA Group) or Usual Care Group (UC Group). Functional capacity of the APA Group significantly increased, by 13.1% (
= 0.000), whereas perceived exertion decreased by 19.7% (
= 0.020). In the same group, the general health evaluated through the questionnaire EORTC-QLQ-C30 increased (
= 0.050). No differences were found in the UC Group. Operation Phalco, creating a network between oncologists, sports medicine physicians and kinesiologists, confirms the importance of structuring a post-operative path where APA should be included as early as possible in the cancer patient care.
Most anticancer treatments act on oxidative-stress pathways by producing reactive oxygen species (ROS) to kill cancer cells, commonly resulting in consequential drug-induced systemic cytotoxicity. ...Physical activity (PA) has arisen as an integrative cancer therapy, having positive health effects, including in redox-homeostasis. Here, we investigated the impact of an online supervised PA program on promoter-specific DNA methylation, and corresponding gene expression/activity, in 3 antioxidants- (SOD1, SOD2, and CAT) and 3 breast cancer (BC)-related genes (BRCA1, L3MBTL1 and RASSF1A) in a population-based sample of women diagnosed with primary BC, undergoing medical treatment. We further examined mechanisms involved in methylating and demethylating pathways, predicted biological pathways and interactions of exercise-modulated molecules, and the functional relevance of modulated antioxidant markers on parameters related to aerobic capacity/endurance, physical fatigue and quality of life (QoL).
PA maintained levels of SOD activity in blood plasma, and at the cellular level significantly increased SOD2 mRNA (≈+77 %), contrary to their depletion due to medical treatment. This change was inversely correlated with DNA methylation in SOD2 promoter (≈−20 %). Similarly, we found a significant effect of PA only on L3MBTL1 promoter methylation (≈−25 %), which was inversely correlated with its mRNA (≈+43 %). Finally, PA increased TET1 mRNA levels (≈+15 %) and decreased expression of DNMT3B mRNA (≈−28 %).
Our results suggest that PA-modulated DNA methylation affects several signalling pathways/biological activities involved in the cellular oxidative stress response, chromatin organization/regulation, antioxidant activity and DNA/protein binding. These changes may positively impact clinical outcomes and improve the response to cancer treatment in post-surgery BC patients.
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•Physical activity prevents antioxidants depletion during cancer treatment.•Antioxidant gene-specific methylation is modulated by physical activity.•Antioxidant marker changes predict variable of distress symptom outcomes.
Hormone therapy following surgery reduces the risk of breast cancer (BC) recurrence and progression of hormone-sensitive BC, especially in postmenopausal women. Despite the antitumor efficacy of ...hormone therapy, particularly of aromatase inhibitors, they cause long-term side effects, mainly bone density reduction. Exercise can slow the rate of bone loss, which reduces the risk of fractures from osteoporosis, and could be an integrative treatment able to mitigate the BC treatment side effects positively impacting bone health. This narrative review aims to discuss studies on the effect of exercise on bone health in BC women undergoing aromatase inhibitors, highlighting the possible role of exercise as complementary to conventional therapies. Additionally, according to the literature revision, exercise practical applications to improve bone health in these patients are summarized.
•AIs increase risk of osteoporosis in Breast Cancer postmenopausal women.•Exercise is an effective complementary therapy reducing risk related to AIs therapy.•High-impact and multicomponent training are effective for osteogenic stimulation.•Exercise can positively affect bone health in BC patients undergoing AIs therapy.
Adapted exercise is an effective non-pharmacological tool to improve functional, cognitive, and psychological parameters in multiple sclerosis (MS), in association with increased quality of life ...(QoL) and decreased disease severity. Adipose tissue, through the production of different adipokines, is involved in regulating energy metabolism and inflammation. Adiponectin, increased in MS, circulates as oligomers of low (LMW), medium (MMW), and high molecular weight (HMW), the latter mediating the main biological effects. The aim of study was to evaluate the effects of 4 months training at moderate intensity 65% heart rate reserve (HRR) on BMI, adiponectin, and QoL in a volunteer with secondary progressive MS. The parameters were evaluated before (T0), after 4 months training (T1), and 6 months after the end of training (T2); total serum adiponectin and its oligomeric profile were evaluated. We found a reduction in BMI (-0.9%) and FAT (-2.6%), an improvement in perceived QoL and a reduced expression of total adiponectin and HMW oligomers together with decreased MS disability level at T1 measured by EDSS. Despite the limitations of a case study, this represent a starting point to understand the influence of exercise in MS and the relationship with adiponectin expression.
Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive ...option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries.
A standardized 32 h dance protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis <3 years, chemotherapy >6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life.
-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention.
Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large.
Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research.
Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase ...cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.
Exercise, including resistance exercise with high loads, has positive hemodynamic responses such as reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), Pressure ...Product Rate (PPR), and estimated myocardial oxygen volume (MVO
). Caffeine (CA), used to improve performance, tends to interfere with BP and HR. This study aimed to analyze the effects of CA supplementation on hemodynamic indicators in Paralympic weightlifting (PP). The exercise was performed on 14 male athletes (32.4 ± 8.5 years; 81.7 ± 21.9 kg) for three weeks. Two conditions were evaluated: supplementation with CA Anhydrous 9 mg/kg and with placebo (PL). The adapted bench press was used, with 5 × 5 at 80% 1RM. We evaluated BP, HR, PPR, and MVO
, before, after, 5, 10, 20, 30, 40, 50, 60 min, and 24 h later. The CA presented higher absolute values in the pressure indicators than the PL, and after 24 h there was an inversion. The HR was higher in the CA and showed a reduction after 10 min. The PPR and MVO
in the CA presented absolute values greater than the PL, and 24 h later there was an inversion. There was no hypotensive effect, but the use of CA did not present risks related to PPR and MVO
, demonstrating the safe use of this supplement in adapted strength sports.
The increasing need to face the problem of sedentarism, especially in the COVID-19 era, induced teachers and researchers to find new intervention methodologies in school context. Active breaks (ABs) ...include brief periods of physical activity as a part of the curriculum. This study aimed to investigate the AB acute responses on attentive skills and mathematical performance and attention in a primary school.
A total of 141 children (aged 9.61 ± 0.82), divided into six classes, participated in this study. Each class was randomly assigned to three groups on the basis of the type of protocol performed during the three ABs scheduled in a school day: fitness (FIT), creativity (CREAT), and control group (CON). At baseline and at the end of interventions, all participants underwent the Stroop Color and Word test (SCWT) and the math test (MATH) to assess the level of attention and mathematical performance, respectively. The degree of enjoyment was evaluated through the modified Physical Activity Enjoyment Scale.
The factorial ANOVA showed significant differences between the FIT and CON in MATH test (
= 0.023) and SCWT (
= 0.034). CREAT and FIT groups showed higher degree of enjoyment than the CON (both
s < 0.001).
This study showed a positive acute impact of AB interventions. FIT positively influenced attentive and math performances more than the CREAT, probably due to the correct work/rest ratio and executive rhythm that allowed children to reach a good level of exertion. This report showed that ABs can be a useful and productive activity to be performed between curricular lessons.
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