Impact of marital status and race on outcomes of patients enrolled in Radiation Therapy Oncology Group prostate cancer trials

Introduction  

Previous studies by our group and others have demonstrated the importance of sociodemographic factors in cancer-related outcomes. The identification of these factors has led to novel approaches to the care of the high-risk cancer patient, specifically in the adoption of clinical interventions that convey similar benefits as favorable sociodemographic characteristics. This study examined the importance of marital status and race as prognostic indicators in men with prostate cancer.     

Impact of body mass index on the predictive ability of body fat distribution for Type 2 diabetes risk in Koreans

Aims The optimal anthropometric measure of obesity or body fat distribution that best predicts the risk of Type 2 diabetes in Asians is unclear. Moreover, it has not been determined whether BMI modifies the effect of body fat distribution on diabetes risk in Asians. Methods We analysed the anthropometric and laboratory data of 7658 non‐diabetic Korean adults (5061 men and 2597 women, aged 20–79 years) who underwent routine medical check‐ups at 5‐year intervals. BMI, waist circumference, waist‐to‐height ratio, and bioelectrical impedance (to calculate fat mass and per cent body fat) were measured at baseline. Results Of the 7658 participants, 278 subjects (3.6%) developed diabetes over 5 years. Each of the anthropometric measures of general obesity (BMI, fat mass, per cent body fat) and central body fat distribution (waist circumference and waist‐to‐height ratio) was a good predictor of Type 2 diabetes. However, when the areas under the receiver‐operating characteristic curves were compared, BMI (0.697; 95% CI, 0.669–0.725), waist circumference (0.709, 0.682–0.736) and waist‐to‐height ratio (0.718, 0.692–0.743) were better predictors of diabetes risk than fat mass (0.672, 0.643–0.700) or per cent body fat (0.657, 0.628–0.686). In the low‐ (< 23 kg/m²) and mid‐ (23–27 kg/m²) BMI groups, the addition of waist‐to‐height ratio or waist circumference to BMI could improve the prediction of diabetes risk. Conclusions BMI, waist circumference and waist‐to‐height ratio were good predictors of Type 2 diabetes risk in Koreans. In non‐obese or less obese subjects, measures of central body fat distribution can help improve the prediction of Type 2 diabetes risk when added to measures of general obesity.     

Erratum: Correction of Nomenclature of Mutations

[This corrects the article on p. 1111 in vol. 26, PMID: 21860566.].     

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for hERα and hERβ with IC₅₀ values of 1.20 ×10⁻⁷ g/ml and 1.00×10⁻⁷ g/ml, respectively. LNE induced 17β-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on hER α and β than other fractions. Our results indicate that LNE had higher binding affinities for hERβ than hERα, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.     

GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma

While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N-acetylgalactosaminyltransferase (GalNAc-T14), is highly inversely correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here, we showed that GalNAc-T14 expression was positively associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9, the expression of which was increased in a GalNAc-T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the β-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of β-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival and increased hazard risk, suggesting that targeting β-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.     

Digital analysis yields more reliable and accurate measures of dermal and epidermal thickness in histologically processed specimens compared to traditional methods

Changes in the thickness of the dermis and epidermis have been described in the scenario of tissue expansion as well as inflammatory skin processes (psoriasis, contact hypersensitivity and so on). These changes have previously been quantified using ocular micrometers to obtain and then average a limited number of spot measurements, leading to suboptimal accuracy. We describe a rapid method of using freely available ImageJ software to analyze digitized images of fixed skin specimens. By determining the cross‐sectional area and surface length of a skin layer, a simple calculation produces more accurate and reproducible measurements of its thickness compared to historical methods, with excellent inter‐rater reliability.