Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

Since the publication of this paper, the authors noticed an error in Fig. 1. The X-axis on all the figure panels should read 'Time (years)', not 'Time (months)'. The corrected Fig. 1 is shown below.

Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

BACKGROUND: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association. METHODS: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014. The primary endpoint was time to development of RIS. RESULTS: We identified 419 patients with RIS. Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1.37; 95% CI: 1.08-1.72; P=0.009). In the multi-variable model, older age (HR 2.11; 95% CI 1.83-2.43; P<0.001) and chemotherapy for the first malignancy (HR 1.61; 95% CI 1.26-2.05; P<0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect. CONCLUSIONS: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of RIS.

A prospective multicentre phase III validation study of AZGP1 as a biomarker in localized prostate cancer.

BACKGROUND: Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. PATIENTS AND METHODS: In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). RESULTS: In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1-1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2-6.6; P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5-9.5; P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1-3.3; P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1-3.4; P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. CONCLUSION: Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.

Protective effect of the polarity of macrophages regulated by IL-37 on atherosclerosis.

As an anti-inflammatory cytokine, interleukin-37 (IL-37) provides certain protective effects against inflammatory and autoimmune diseases. Recent reports indicate that IL-37 is expressed in foam cells of atherosclerotic plaques in both the coronary and carotid arteries of humans, suggesting the possible involvement of IL-37 in the pathogenesis and progression of atherosclerosis. Current evidence supports the protective role that IL-37 plays against atherosclerosis via the regulation of different subtypes of macrophage. Atherosclerosis was induced in apolipoprotein E -/- mice through diet, and the mice were then given IL-37 to observe patterns in the aorta plaque. Furthermore, human peripheral blood-derived monocytes were cultured for seven days to induce the differentiation of macrophages. Specifically, we observed the effect of IL-37 on oxygenated low density lipoprotein (ox-LDL)-induced macrophage polarity, in addition to conducting an expressional assay of the M1 cell markers tumor necrosis factor (TNF)-α and CD86 and the M2 marker CD206. IL-37 effectively decreased the area ratio between the aorta plaque and vascular cavity. We also observed that M1 macrophages can be induced from peripheral monocytes by ox-LDL, with significant elevation of marker molecules TNF-α and CD86. The co-stimulation of IL-37 and ox-LDL, however, inhibited the induction of M1 cells and facilitated the transformation of macrophages into M2 cells, as supported by the elevation of cell-specific marker CD206. These results indicate that IL-37 can prevent atherosclerosis by modulating macrophage polarity.

Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cells.

The article "Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cells" by Y. Wang, Y.-R. Zhao, A.-Y. Zhang, J. Ma, Z.-Z. Wang, X. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (9): 2087-2097 has been withdrawn.

Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cells.

OBJECTIVE: Elevated expression of caspase-8 (CASP8) and Fas-associating protein with a novel death domain (FADD)-like apoptosis regulator (CFLAR) increases sensitivity against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis, but with an unclear mechanism. A previous study showed decreased microRNA-20a (miR-20a) expression in hepatocellular carcinoma (HCC) patient's tumor tissues. Bioinformatics analysis showed potential targeting relationship between the 3-UTR of CFLAR and miR-20a. This study investigated if miR-20a played a role in regulating CFLAR expression and HCC apoptosis. PATIENTS AND METHODS: Expressions of miR-20a and CFLAR in model rat HCC tissues were compared to normal tissues. HCC patients were also collected for measuring miR-20a and CFLAR expressions between tumor and adjacent tissues. Dual-luciferase reporter gene assay was performed to evaluate the relationship between miR-20a and CFLAR. Cultured HepG2 cells treated with 120 ng/ml TRAIL were mixed with miR-20a mimic and/or si-CFLAR followed by measurement of Caspase-8/3 activity and cell apoptosis by flow cytometry, cell proliferation by MTT assay and protein expression by Western blot. RESULTS: MiR-20a expression was significantly decreased in rat HCC tissues, while CFLAR was over-expressed. HCC patients had lower miR-20a level and higher CFLAR level in tumor tissues. MiR-20a targeted 3'-UTR of CFLAR to inhibit its expression. TRAIL remarkably up-regulated CFLAR expression, whilst inhibiting miR-20a expression and/or silencing CFLAR significantly potentiated caspase-8 and caspase-3 activity, enhanced sensitivity of HepG2 cells towards TRAIL-induced cell apoptosis, and decreased cell proliferative function. CONCLUSIONS: HCC had lower miR-20 and higher CFLAR expression. MiR-20a targeted and inhibited CFLAR expression, facilitated activation of caspase-8 and caspase-3, and enhanced sensitivity of HepG2 cells towards TRAIL-induced apoptosis, and subsequently reduced cell proliferation.

Ethnic characteristics of mental disorders in five U.S. communities.

The study examined the ethnic ratio of 16 DSM-III mental disorders among White, Black, Hispanic, and Asian Americans. A total of 18,126 residents from 5 sites and 2,939 residents from the Epidemiological Catchment Area's Los Angeles site were studied separately. Logistic regression analysis was performed. Results showed that Blacks were significantly less likely than Whites to have major depressive episode, major depression, dysthymia, obsessive-compulsive disorder, drug and alcohol abuse or dependence, antisocial personality, and anorexia nervosa, but they were significantly more likely than Whites to have phobia and somatization. Lifetime prevalence rates of schizophrenia, obsessive-compulsive disorder, panic, and drug abuse or dependence were significantly lower among Hispanics than among Whites. Asians also had significantly lower rates than Whites of schizophreniform, manic episode, bipolar disorder, panic, somatization, drug and alcohol abuse or dependence, and antisocial personality. Compared with the overall findings, ethnic differences at the Los Angeles site were lessened between Blacks and Whites, enhanced between Hispanics and Whites, and basically unchanged between Asians and Whites.

Family and cultural correlates of depression among Chinese elderly.

This study hypothesized that depressive experiences of the elderly could be aggravated by universal factors such as low social status, poor health, financial strain, and unhealthy lifestyle, as well as by factors specific to an indigenous socio-cultural environment (stressful family dynamics) of a given population. Three hundred and fifty Chinese subjects aged 65 or older were interviewed either at their homes or in the geriatric out-patient clinic of Beijing Hospital. Hierarchical logistic regression was used to examine significant predictors of depression. Results showed that certain social status, poor physical health, financial strain, unhealthy lifestyle, and stressful family situation explained 47 percent of the variance in depression. However, stressful family situation alone explained 13 percent of the variance in depression, indicating that family factors were important predictors of depression for Chinese elderly. Furthermore, this study demonstrated for the first time that verbal abuse within Chinese families is a significant correlate of depression among the elderly. Cultural implications of these findings are discussed.

Anthropophobia: its meaning and concomitant experiences.

This study investigated the essential feature and concomitant experiences of anthropophobia, a culturally specific phobic disorder in China and Japan. One hundred and fifty subjects, including 50 anthropophobic, 50 neurasthenic and 50 normal subjects, were recruited from hospitals and downtown residential areas in Beijing. Measures of anthropophobic symptoms and DSM-III-R depressive and anxiety symptoms were administered to all subjects. Nonparametric analysis of variance, analysis of variance (ANOVA and MANOVA) and Fisher's exact test were performed to examine group differences on each symptomatic item of the three measures. Results indicate that the core anthropophobic symptoms include a fear of making eye contact with others and a fear of being watched by others, which essentially express fears of others' judgement or opinion of oneself. Anxiety and depression are associated features of anthropophobia. However, these concomitants are experienced more cognitively and less somatically in the case of anthropophobia than neurasthenia.

[Risk factors of breast cancer among women in Tianjin, China and Adelaide, Australia].

In order to study the possible explanation of the marked difference in the incidences of breast cancer between Chinese and Australian women, the authors have compared and analysed the results of two case-control studies completed recently in Tianjin, China and Adelaide, Australia. Of 9 potential risk factors studied, 8 are significantly higher in Adelaide (Ad) women than in Tianjin women. Women in Ad were much taller, heavier, more obese, earlier at menarche, later at first full-term pregnancy, more nulliparous, less parity, more in history of breast cancer in first degree relatives. In addition, they were well educated. The findings obtained by analysis of logistic regression model indicated that increased risk for breast cancer was associated with early menarche, late first full-term pregnancy, less parity, nulliparity, histories of benign breast diseases and breast cancer in first degree relatives in the Tianjin study, but not in Ad study. Late menopause and history of oral contraceptive were not associated with the increased risk in both studies. These factors being not associated with breast cancer in Ad women was unexpected. The explanation of the indefinite findings in Ad study was due to the fact that the level of the risk factor is higher, more uniform, and lack of stratum. The difference in the level of the risk factor will not appear among cases and controls in case-control study, and significance of the risk factor therefore may not be found. According to data on diet survey in these two cities, the amount of fat intake was significantly higher in Ad women than in Tianjin women.(ABSTRACT TRUNCATED AT 250 WORDS)

The association between breast cancer and diet and other factors.

To explore the effects of diet and other factors on breast cancer development, a case-control study was conducted in Tianjin between 1986-87. After adjusting for confounding factors, it was found that factors associated with increased risk of breast cancer included --early age at menarche; late age at menopause; late age at first birth; high Qutelet's index; histories of breast wound, disease and benign tumor; and a family history of malignant tumor, high fat, high calorie, low vegetable intake; elevated serum cholesterol and LDL-cholesterol; and lower levels of serum HDL-cholesterol and whole blood selenium.

Gene expression analysis of Dupuytren's disease: the role of TGF-beta2.

Dupuytren's disease is characterised by nodular fibroblastic proliferation of the palmar fascia leading to contracture of the hand. Transforming growth factor beta (TGF-beta) is thought to play a role in its pathogenesis. We performed a cDNA microarray analysis of Dupuytren's diseased cord tissue with an emphasis on TGF-beta isoforms. Normal-appearing transverse ligament of the palmar fascia from adjacent to the diseased cord and palmar fascia from patients undergoing carpal tunnel release were used as controls. TGF-beta gene expression was confirmed by quantitative real-time polymerase chain reaction. Over 20 unique genes were found to be significantly up-regulated, including several previously reported genes. A dominant increase in TGF-beta2 expression was seen in the cord tissue, whereas TGF-beta1 and TGF-beta3 were found not to be significantly up-regulated. Quantitative real-time polymerase chain reaction confirmed these findings. This gene expression profile allows for further experiments that may eventually lead to gene therapy to block the development and progression of Dupuytren's disease clinically.

U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia.

Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Homozygous or heterozygous deletion of U19/Eaf2 resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostate intraepithelial neoplasia. Within the mouse prostate, U19/Eaf2 deficiency enhanced cell proliferation and increased epithelial cell size. The knockout mice also exhibited cardiac cell hypertrophy. These data indicate a role for U19/Eaf2 in growth suppression and cell size control as well as argue for U19/Eaf2 as a novel tumor suppressor in multiple mouse tissues. The U19/Eaf2 knockout mouse also provides a unique animal model for three important cancers: lung adenocarcinoma, B-cell lymphoma and hepatocellular carcinoma.

Inhibition of ceramide-redox signaling pathway blocks glomerular injury in hyperhomocysteinemic rats.

Ceramide-activated NAD(P)H oxidase has been reported to participate in homocysteine (Hcys)-induced abnormal metabolism of the extracellular matrix (ECM) in rat glomerular mesangial cells. However, it remains unknown whether this ceramide-redox signaling pathway contributes to glomerular injury induced by hyperhomocysteinemia (hHcys) in vivo. The present study was designed to address this question, defining the role of ceramide and activated NAD(P)H oxidase in the development of hHcys-induced glomerular injury. Uninephrectomized Sprague-Dawley rats were fed a folate-free diet for 8 weeks to produce hHcys and the de novo ceramide synthesis inhibitor myriocin or the NAD(P)H oxidase inhibitor apocynin was administrated. Rats with folate-free diet significantly increased plasma Hcys levels, renal ceramide levels, and NAD(P)H oxidase activity accompanied by marked glomerular injury. Treatment of rats with myriocin significantly reduced ceramide levels and improved glomerular injury, as shown by decreased urinary albumin excretion and reduced glomerular damage index. ECM components changed towards to normal levels with decreased tissue inhibitor of metalloproteinase-1 and increased matrix metalloproteinase-1 activity. NAD(P)H oxidase activity and Rac GTPase activity were reduced by 69 and 66%, respectively. In rats treated with apocynin, similar beneficial effects in protecting glomeruli from hHcys-induced injury were observed. These results support the view that de novo ceramide production is involved in Hcys-induced NAD(P)H oxidase activity in the kidney of hHcys rats and indicate the important role of ceramide-mediated redox signaling in hHcys-induced glomerular injury in rats.

Life satisfaction among Chinese elderly in Beijing.

The present study examined correlates of life satisfaction among 350 Chinese elderly aged 65 or older. Subjects consisted of a clinic sample (n = 200) and a randomly selected community sample (n = 150) recruited from the same area in Beijing. Linear regression analysis was performed, using health, financial status, and family support as independent variables. Results showed that the regression model explained 38 percent of the variance in life satisfaction in the total sample, 34 percent and 43 percent of the variance respectively in the clinical and community samples. Life satisfaction was significantly predicted by health and financial status among community elderly and by health, financial status, as well as family support among outpatient elderly. Findings suggest that the socio-cultural context has exerted important impacts on the Chinese elderly's life satisfaction.

Sociocultural contexts of anthropophobia: a sample of Chinese youth.

BACKGROUND: Anthropophobia, a subtype of social phobia, is prevalent in Chinese and Japanese societies. This study investigated sociocultural influences on the course of this culturally specific mental disorder. METHOD: One hundred and fifty subjects, including 50 anthropophobic, 50 neurasthenic, and 50 community subjects, were interviewed in Beijing, China for the assessment of their early life experiences (child-parent relationships and sexual experiences), collectivism disposition, sexual attitudes, and communication behaviors. Logistic and linear regression analyses were performed to examine significant predictors of the occurrence and the symptom level of anthropophobia. RESULTS: Regression models explained 69% of variance in the diagnosis and 57% of variance in the symptom level of anthropophobia among anthropophobic and community subjects. They also explained 48% and 47% of variance respectively in the diagnosis and the level of symptoms among anthropophobic and neurasthenic subjects. Anthropophobic subjects had more problematic relationships with parents than did community and neurasthenic subjects. They also exhibited significantly stronger characteristics of collectivism than did community subjects. Sexual contact with a non-family member prior to age 19 and a feeling of discomfort when interacting with the opposite sex were significantly associated with the diagnosis and symptom level of anthropophobia. CONCLUSIONS: It was concluded that anthropophobic subjects' early sexual experiences and need for parental approval shaped their conformity to social norms and negative sexual attitudes, which were reinforced by the collective-orientated cultural environment, and contributed to the development of anthropophobia.

Cultural correlates of self perceived health status among Chinese elderly.

This study examines self-perceived physical and mental health among 213 Chinese elderly who visited the Geriatric Outpatient Clinic of Beijing Hospital, the People's Republic of China. The study hypothesizes that cultural factors, specified by family relations, along with demographic factors, number of diseases, economic well-being, and living conditions have a significant impact on subjects self-perceived health status. Pearson correlation, linear and logistic regression analyses are performed. Results indicate that age, number of diseases, perceived family respect, neighborhood relations, and percentage of income spent on rent are significant predictors of self-perceived physical health. These same factors plus preference to live with a son and personal monthly income are significant predictors of self-perceived mental health. Socio-cultural implications of these findings are examined.