The impact of maximal strength training on quality of life among women with breast cancer undergoing treatment.

Cancer rehabilitation programs mainly involve endurance cardio training while little attention has been paid to strength training. Breast cancer (BC) patients lose muscle strength while undergoing adjuvant treatment, thus affecting daily activities and quality of life. Maximal strength training, with an emphasis on velocity in the concentric phase, improves maximal strength and muscle force development characteristics. However, the effect of maximal strength training on quality of life for BC patients undergoing treatment remains elusive. Consequently, the aim of this study was to evaluate the effectiveness of maximal strength training in Health related quality of life in women with newly diagnosed BC. MATERIALS AND METHODS: 55 BC patients with disease stage I-III were randomized into a training group and control group. The training group performed maximal strength training twice a week for 3 months, whereas the control group followed prescribed treatment without strength training. Overall quality of life was measured by The European Organization for Research and Treatment of Cancer Core Quality of life Questionnaire-C30 and additional BC module BR23 before and after the intervention. RESULTS: The results obtained from pre-tests and those obtained after 3 months of intervention revealed that patients in the training group significantly increased one repetion maximum, by 20.4 kg (20%) (p = 0.001, d = 0.9). Simultaneously, statistically significant alterations were observed in this variable for the control group, one repetition maximum decreased by 8.9 kg (9%) (p = 0.001, d = 0.5). The overall quality of life improved significantly by 13% for the training group with large effect (p = 0.002, d = 0.6), but no relevant changes were observed in the control group (p = 0.44, d = 0.2). Results revealed remarkable changes in overall quality of life after 3-month post-test period between the two groups with large effect (p = 0.002, d = 0.9). The training sessions had helped in diminishing the sense of fatigue by 24% (p = 0.03, d = 0.6), while it had got worse by 25% (p = 0.02, d = 0.4) for the control group. Again, the data on large effect were noticed to differ between the groups (p = 0.01, d = 0.6). CONCLUSION: Maximal strength training for BC patients was well tolerated, safe and feasible and showed strength improvements that led to improved muscle strength and improved overall quality of life. These data certainly support the therapeutic role for maximal strength training in the treatment of BC.

Disentangling the aneuploidy and senescence paradoxes: a study of triploid breast cancers non-responsive to neoadjuvant therapy.

Aneuploid cells should have a reduced proliferation rate due to difficulty in proceeding through mitosis. However, contrary to this, high aneuploidy is associated with aggressive tumour growth and poor survival prognosis, in particular in triploid breast cancer. A further paradox revolves around the observation that, while cell senescence should inhibit proliferation, the senescence marker p16INK4a correlates with poor treatment outcome in patients with a very aggressive triple-negative breast carcinoma (TNBC). In this study, we aim to pour light on the possible relationship of these conundrums with polyploidy of tumour cells. We performed detailed analysis of DNA histogram profiles in diagnostic core biopsies of 30 cases of operable breast cancer and found that near triploidy in TNBC and other forms correlated with weak or no response to neoadjuvant chemotherapy (NAC) as scored by Miller-Payne index. Polyploid cells in operation samples from tumours that were non-responsive to NAC treatment were Ki67 and CD44 positive. In addition, polyploid cells were positive for markers of embryonic stemness (OCT4, SOX2, NANOG) and senescence (p16INK4a). The relationship patterns between p16INK4a and NANOG were heterogeneous, with predominantly mutually exclusive expression but also synergistic and intermediate variants in the same samples. We conclude that the aneuploidy and senescence paradoxes can be explained by the mutual platform of polyploidy, conferring genomic and epigenetic instability as a survival advantage. Such cells are able to bypass aneuploidy restrictions of conventional mitosis and overcome the barrier of senescence by a shift to self-renewal, resulting in progression of cancer.

Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as a context-dependent tumor suppressor.

Trefoil factor 3 (TFF3) is overexpressed in a variety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the S phase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as a tumor suppressor or an oncogene depending on the cellular context.

Survey of autoantibody responses against tumor-associated antigens in thyroid cancer.

BACKGROUND: Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specific serological biomarkers for the diagnosis of various solid cancers. Although the autoimmunity against thyroid tissue specific antigens has been studied extensively, so far, the autoantibody responses against common TAAs such as cancer-testis antigens (CTAs), mutated or differentiation antigens have not been comprehensively analyzed in patients with thyroid cancer. OBJECTIVE: The current study aims to characterize the frequency of autoantibody responses against common TAAs in patients with thyroid cancer and benign thyroid nodules. METHODS: A phage-displayed antigen microarray comprising 65 TAAs was produced and tested with sera from 53 patients with thyroid cancer, 90 patients with benign thyroid nodules and 96 cancer-free individuals, 100 melanoma, 54 breast cancer and 14 lung cancer patients as controls. RESULTS: A panel of 6 TAAs was identified that preferentially reacted with sera from patients with thyroid cancer. The top ranked antigen in this panel was GAGE1 eliciting autoantibody response in 6% of patients with thyroid cancer but not with benign nodules, whereas no reactivity to other CTAs was detected in the sera from patients with thyroid cancer. CONCLUSIONS: Although six TAAs, including one CTA, showed thyroid cancer-associated reactivity, overall, spontaneous humoral immune responses against TAAs are rare in thyroid cancer and their utility for the development of non-invasive assay for the differential diagnosis of thyroid nodules is limited.