Association of Empirically Derived Food-Based Inflammatory Potential of the Diet and Breast Cancer: A Hospital-Based Case-Control Study

BackgroundDiet may be a modifiable factor in the prevention of breast cancer (BC) by modulating inflammation. We used a food-based empirical dietary inflammatory index (FDII) to evaluate the association between FDII and odds of breast cancer in Iranian women.MethodsThe present case-control study carried out on 150 age-matched women with newly diagnosed breast cancer and controls. Data for dietary intake and anthropometric measures were collected. FDII score was developed according to participants dietary intakes of 27 pre-defined food groups. Multivariate odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the association of empirically derived food-based inflammatory potential of the diet and breast cancer.ResultsThe odds ratios of BC according to quartiles of FDII score by multivariate logistic regression models indicated the FDII score was significantly associated with BC risk (OR: 2.38; 95% CI: 1.23-4.59, P _trend = .04). After controlling confounders, multivariate logistic regressions remained significant which revealed in participants at the fourth quartile of FDII score chance of breast cancer was 2.8 times higher than participants in the first quartile.ConclusionsThe results of our study suggested that more pro-inflammatory diet (higher FDII scores) was associated with increased BC risk. These findings suggest that developing an effective dietary modification based on FDII may reduce risk of BC.     

Genetic variants in fas signaling pathway genes and risk of gastric cancer

Populations in north central China are at high risk for gastric cancers (GC), and altered FAS‐mediated cell signaling and/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling‐related genes using a pathway‐based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome‐wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene‐ and pathway‐based associations were tested using the adaptive rank‐truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway‐based associations were observed for Fas signaling with risk of overall GC (p = 5.5E‐04) and GCA (p = 6.3E‐03), but not GNCA (p= 8.1E‐02). Among examined genes in the Fas signaling pathway, MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2 and IKBKB were associated with risk of GC (nominal p < 0.05), and FAF1 and MAPK8 were significantly associated with risk of both GCA and GNCA (nominal p< 0.05). Our examination of genetic variation in the Fas signaling pathway is consistent with an association of altered Fas signaling and/or apoptosis with risk of GC. As one of the first attempts to investigate a pathway‐level association, our results suggest that these genes and the Fas signaling pathway warrant further evaluation in relation to GC risk in other populations.     

Patterns of androgen deprivation therapies among men diagnosed with localised prostate cancer: A population-based study

AimMany men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort.Methods and materialsData were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA) < 50 ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach.ResultsThe cumulative incidence of castration at 10 years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4 years in the deferred treatment high-risk group to 17 years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT.ConclusionWhen initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment.     

基质金属蛋白酶-1（-1607）1G/2G基因多态性与鼻咽癌相关性研究

目的研究基质金属蛋白酶-1（matri xmetalloproteinases-1,MMP-1）（-1607）1G/2G基因单核苷酸多态性与云南汉族鼻咽癌发病风险、各临床参数及预后相关性。方法按病例对照研究,利用聚合酶链反应-限制性片段长度多态性（restriction fragment lengthpolymorphism-PCR,RFLP-PCR）,对241例云南籍汉族鼻咽癌患者和272例云南籍汉族健康对照进行基因分型,分析基因型与云南汉族鼻咽癌发病风险及预后关系。结果分别携带1G2G、2G2G基因型个体罹患鼻咽癌风险性是携带1G1G基因型者3.10倍和9.93倍;2G等位基因与T分期、颈淋巴结转移、临床分期明显相关（P〈0.05）。吸烟与MMP-1（-1607）2G等位基因存在相加交互作用;MMP-12G等位基因与患者预后不良相关,且2G2G基因型为独立预后影响因素。结论MMP-1（-1607）1G/2G多态性是云南汉族鼻咽癌遗传易感因素,与吸烟暴露呈现交互作用,同时与鼻咽癌预后相关。     

Jasmine tea consumption and upper gastrointestinal cancer in China

Introduction  

Epidemiological data on green/jasmine tea and esophageal as well as gastric cancer are limited and inconclusive.     

Frequent concomitant epigenetic silencing of the stress‐responsive tumor suppressor gene CADM1, and its interacting partner DAL‐1 in nasal NK/T‐cell lymphoma

Nasal NK/T‐cell lymphoma (NL) is a rare but clinically important entity of lymphoma. Its preferential incidence in Orientals but not Caucasians suggests possible genetic predisposition. 11q deletion is common in NL, indicating certain tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1), and its partner DAL‐1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were detected in 2 NL and 4 of 8 (50%) of non‐Hodgkin lymphoma (NHL) cell lines, but not in normal NK cells and normal PBMC. Absence of CADM1 protein was also detected in NL cell lines. 5‐aza‐2′‐deoxycytidine (Aza) demethylation or genetic knockout of both DNMT1 and 3B genes restored CADM1 and DAL‐1 expression. CADM1 methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly, DAL‐1 was epigenetically inactivated in NL cell lines and virtually all the tumors with methylated CADM1. A significant correlation between the methylation of both genes was found (p < 0.0001). Homozygous deletion of CADM1 was detected in only 3 of 18 (17%) of tumors. The stress‐response of CADM1 was abolished when its promoter becomes methylated. Our results demonstrate a frequent, predominant epigenetic silencing of CADM1 and DAL‐1 in NL, which likely play a synergic role in NL pathogenesis. © 2008 Wiley‐Liss, Inc.     

角蛋白19、癌胚抗原mRNA的表达与微转移的探测

目的探讨癌症患者在开始接受治疗时是否已发生血液循环中癌细胞的微转移.方法以角蛋白19(K19)-mRNA及癌胚抗原(CEA)-mRNA两基因的表达为标记物;应用巢式-反转录聚合酶链反应(Nested-RT-PCR)进行扩增,经PAG后进行观察.结果结肠癌组75例患者的门静脉血中肯定有转移者36例(48.0%);其中35例之周围血有8例(22.86%)为阳性.卵巢癌组50例患者之骨髓测得25例(50.0%)为阳性,其周围血22例中只有3例(13.63%)为阳性,20例未经化疗之结直肠癌患者作了周围血的复查,阳性仍占20%.结肠癌随临床Duke's分期早晚其阳性率亦随之上升;病理型态分化程度之高低与微转移亦呈正相关.结论结肠癌、卵巢癌临床早期已有癌细胞发生微转移.单凭手术消灭不了癌细胞,必须及早化疗.K19可作为检测卵巢癌的生物指标.而结直肠癌则以K19及CEA联合应用更可靠.标本采集,结肠癌以门静脉血,卵巢癌以骨髓为首选.     

Human mesenchymal stem cells respond differentially to platelet preparations and synthesize hyaluronic acid in nucleus pulposus extracellular matrix

BACKGROUND CONTEXTIn recent years, autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have been used as treatments for disc-related pain. A better understanding of the effects of leukocyte-rich (LR) versus leukocyte poor (LP-) PRP on bone marrow derived human mesenchymal stem/progenitor cells (hMSCs) is likely to improve future research studies, clinical practice and care for patients with chronic discogenic back pain.PURPOSEThe primary aim of this study is to determine the effects of LR-PRP and LP-PRP on the proliferation and migration of hMSCs in pig nucleus pulposus (NP) extracellular matrix (ECM). The secondary aim is to characterize hMSC-dependent expression of the matrix remodeling enzymes metalloproteinases MMP-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinases TIMP-2, and to determine whether transplanted hMSCs can synthesize hyaluronic acid (HA).STUDY DESIGNControlled laboratory study.METHODSBone marrow-derived culture expanded hMSCs were seeded onto pig NP and cultured with LR-PRP, LP-PRP or serum/platelet releasate (PR). The same conditions without hMSCs were used as controls. hMSC proliferation, migration and dispersion was assessed via fluorescent microscopy, while HA synthesis, MMP-2, MMP-3, MMP-9, and TIMP-2 protein levels were assessed via enzyme linked immunosorbent assay. All funding was provided by a 501c(3) research foundation and does not have any commercial or sponsorship interests.RESULTSLP-PRP and PR cultures resulted in higher hMSC proliferation, migration, dispersion, and MMP-2 expression. LP-PRP cultures resulted in the highest HA production. LR-PRP cultures resulted in lower hMSC proliferation, negligible migration and dispersion, increased MMP-9 expression and lower HA production.CONCLUSIONSHuman bone marrow-derived hMSCs seeded onto pig NP ECM are capable of synthesizing HA, indicating a transition towards a NP cell phenotype. This process was most enhanced by LP-PRP and marked by increased hMSC proliferation, MMP-2 production, HA synthesis and reduced MMP-9 levels.CLINICAL SIGNIFICANCELP-PRP and PR, with or without hMSCs, may provide better outcomes than LR-PRP in lab investigations and clinical trials for discogenic pain. Bone marrow-derived hMSCs may hold promise as a treatment for disc degeneration.     

The Relationship between Plasma Al Levels and Multi-domain Cognitive Performance among In-service Aluminum-exposed Workers at the SH Aluminum Factory in China: A Cross-sectional Study

BackgroundAluminum (Al) exerts neurotoxic effects following overexposure. We previously reported worse cognitive performance in workers exposed to Al than non-exposed individuals. Cognition involves multiple domains. The effect of Al on multi-domain cognition has been studied for decades, but still remains controversial.ObjectiveTo explore the relationship between plasma Al levels and multi-domain cognitive performance among in-service aluminum-exposed workers at the SH Aluminum Factory in China and identify possible types of early cognitive damage caused by exposure to aluminum.MethodsEight hundred thirty-one in-service aluminum-exposed workers at the SH Aluminum Factory in China were investigated. The plasma Al concentrations were measured using inductively coupled plasma-mass spectrometry (ICP-MS) and served as an internal exposure indicator. The participants were divided into four subgroups based on the quartiles of plasma Al concentrations, namely, the Q₁, Q₂, Q₃, and Q₄ subgroups. Cognitive function was assessed using the Mini-mental State Examination (MMSE) and the clock-drawing test (CDT). Multi-domain cognition was evaluated using sub-tests of the MMSE and the CDT.ResultsThe average plasma Al concentration was 15.26 (8.28, 27.02) μg/L. The neurobehavioral tests showed negative correlations between plasma Al levels and total CDT scores and executive/visuospatial cognitive performance, and a positive correlation between plasma Al levels and CDT-position errors (all P<0.05). Additionally, dose-response relationships between higher plasma Al levels and lower total CDT scores, worse executive/visuospatial cognitive performance, and more error rates in the CDT-position were observed (all P_trend<0.05). However, no significant correlations or trends were observed between plasma Al levels and other cognitive domains (all P>0.05). The results from the multivariate logistic regression model and restricted cubic spline models of dose-response relationships were consistent with the results obtained from the general linear model. All potential confounders, such as age, marital status, education, income, type of work, and smoking and drinking habits, were considered.ConclusionBased on the results, aluminum exposure may exert a substantial effect on impairing executive/visuospatial functions in multi-domain cognition at the early stage, particularly the identification of spatial positions.