Successful weight loss maintenance: A systematic review of weight control registries

Weight loss maintenance is a major challenge for obesity treatment. Weight control registries can be useful in identifying psychological and behavioural factors that could contribute to better long‐term success. The objective of this study is to describe the existing weight control registries and their participants and identify correlates of weight loss maintenance. A comprehensive search of peer‐reviewed articles published until November 2018 was conducted in PubMed, Web of Science, and Scopus. Studies that reported results from weight control registries were considered. Fifty‐two articles, corresponding to five registries (the United States, Portugal, Germany, Finland, and Greece), were included. Registries differed in inclusion criteria and procedures. Of 51 identified weight loss and maintenance strategies, grouped in 14 domains of the Oxford Food and Activity Behaviors taxonomy, the following were the most frequently reported: having healthy foods available at home, regular breakfast intake, increasing vegetable consumption, decreasing sugary and fatty foods, limiting certain foods, and reducing fat in meals. Increased physical activity was the most consistent positive correlate of weight loss maintenance. To our knowledge, this is the first systematic review of information about successful weight loss maintenance obtained from weight control registries. Key common influential characteristics of success were identified, which can inform future prospective studies and weight management initiatives.     

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.     

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer.

Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume-corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival.     

Antigen targeting to endosomal pathway in dendritic cell vaccination activates regulatory T cells and attenuates tumor immunity

Lymphoma cells are malignant cells of the T- or B-cell lineage that often express many surface markers inappropriately, yet are not recognized as abnormal by the immune system. We modeled this situation by inoculating ovalbumin-expressing E.G7-OVA lymphoma cells into mice that expressed ovalbumin as a self antigen in pancreatic islets, and investigated the efficacy of dendritic cell (DC) vaccination in these mice. Although vaccination with DC-expressing ovalbumin induced strong cytotoxic T-cell immunity, which led to clearance of E.G7-OVA lymphoma cells in naive C57BL/6 mice, DC vaccination was ineffective in mice expressing ovalbumin as a self antigen. Antigen modification to increase its processing via the endosomal processing pathway dramatically increased CD4 T-cell activation but paradoxically, impaired the protective effect of DC vaccination even in naive mice. Depletion of CD25⁺ T cells (regulatory T cells [Tregs]) prior to vaccination restored the efficacy of DC vaccination and allowed eradication of lymphoma also in mice expressing ovalbumin as a self antigen. We conclude that lymphoma cells may be eradicated using DC vaccination if activation of CD25⁺ Tregs is simultaneously inhibited, and that intentionally enhanced endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell help toward stimulation of Tregs.      

Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer. METHODS: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry. RESULTS: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5 and tenascin-C positivity did not correlate with the level of invasion. MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent. CONCLUSIONS: MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin.     

Distinct ligand binding properties of Mac‐2‐binding protein and mouse cyclophilin C‐associated protein*

Human Mac‐2‐binding protein (Mac‐2‐BP) is a secreted glycoprotein that is widely expressed. It binds to the human macrophage‐associated lectin Mac‐2 and has been suggested to have a role in host defence. Mouse cyclophilin C‐associated protein (mCyCAP) is also a secreted glycoprotein that binds with high affinity to cyclophilin C in the absence of the immunosuppresive drug cyclosporin A. The two proteins share a similar domain structure and considerable sequence identity, including a highly conserved scavenger receptor cysteine‐rich domain, and both of them exert their function within the immune system. To elucidate whether these molecules are also functional homologues, we compared their ligand binding properties using cell lines which express Mac‐2‐BP or mCyCAP as well as transfected cell lines stably expressing mCyCAP or a mutant version lacking the scavenger domain. These experiments show that Mac‐2‐BP is unable to bind to either human or mouse cyclophilin C and thatmCyCAP cannot bind to Mac‐2. The scavenger domain is not required for the interaction between mCyCAP and cyclophilin C. We conclude that these proteins may be part of a larger family of proteins of immunological importance in which closer functional homologues might exists.