Negative Impact of 25-hydroxyvitamin D Deficiency on Breast Cancer Survival

Background: Low 25-hydroxyvitamin D [25(OH)D] levels in serum are associated with breast cancer risk. This study was conducted to determine the impact of 25(OH)D deficiency on survival of breast cancer patients. Methods: In a retrospective cohort study of 303 patients diagnosed with breast cancer during 2011-2012 at the National Cancer Institute Thailand, all cases were followed up for 7 years. The 25(OH)D was measured by high-performance liquid chromatography (HPLC). Clinical and pathological data were collected. The Chi-square test, Kaplan-Meier and Cox regression model were used to assess the association between 25(OH)D levels and risk of death. Results: Of the 303 cases aged between 24 and 78 years 51 (16.8%) died during follow-up from any cause. The mean 25(OH)D levels was 25.1±7.54 ng/ml (8.2 – 61.0 ng/ml). Thirty-three patients (10.9%) were stratified as inadequate or deficient group (<16 ng/ml) with mean survival time of 60.65 months compared to 76.24 months in insufficient or sufficient group (≥16 ng/ ml). Multivariate analysis adjusted for age, body mass index, stage, lymph node metastases, and immunohistochemical (IHC) findings (ER, PgR, HER-2, Ki-67 and P53) showed that patients with low 25(OH)D levels (<16 ng/ml) at diagnosis had a significantly higher risk of death (hazard ratio = 2.5-2.9) than the group with high 25(OH)D levels (≥16 ng/ ml). Conclusion: A concentration of 25(OH)D below 16 ng/ml was found to be independently associated with poor survival in breast cancer patients, regardless of age, lymph node status, stage or breast cancer subtype. An investigation of potential benefit of 25(OH)D supplements appears warranted.     

AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker

Aldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated with tumorigenic transformation of human mammary epithelial cells. This study demonstrated that AKR1B10 was overexpressed in 20 (71.4%) of 28 ductal carcinomas in situ, 184 (83.6%) of 220 infiltrating carcinomas and 28 (87.5%) of 32 recurrent tumors. AKR1B10 expression in breast cancer was correlated positively with tumor size (p = 0.0012) and lymph node metastasis (p = 0.0123) but inversely with disease-related survival (p = 0.0120). Univariate (p = 0.0077) and multivariate (p = 0.0192) analyses both suggested that AKR1B10, alone or together with tumor size and node status, is a significant prognostic factor for breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Importantly, AKR1B10 in the serum of breast cancer patients was significantly increased to 15.18 ± 9.08 ng/ml [n = 50; 95% confidence interval (CI), 12.60-17.76], with a high level up to 58.4 ng/ml, compared to 3.34 ± 2.27 ng/ml in healthy donors (n = 60; 95% CI, 2.78-3.90). In these patients, AKR1B10 levels in serum were correlated with its expression in tumors (r = 0.8066; p < 0.0001). Together our data suggests that AKR1B10 is overexpressed in breast cancer and may be a novel prognostic factor and serum marker for this deadly disease.     

Association between Circulating Vitamin D,the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form 1,25(OH)2D to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by pairedt-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancerpatients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT (8.91±4.31) and Tt (9.15±5.25) genotypescompared to control ((21.3±8.31) and (19.3±7.68); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.     

JAG1和Notch3在乳腺癌组织中的表达及预后价值

目的探讨JAG1和Notch3在乳腺癌组织中的表达水平及预后意义。方法通过在线Oncomine数据库和Kaplan-Meier Plotter数据库分析JAG1和Notch3在乳腺癌组织中的表达情况及对预后的影响。收集2008年1月至2013年12月乳腺浸润性导管癌组织及配对癌旁组织各80例,采用实时荧光定量PCR(QPCR)和免疫组织化学SP法分别检测JAG1和Notch3的mRNA和蛋白水平,分析JAG1和Notch3蛋白表达与乳腺癌临床病理特征和总生存时间(OS)的关系。多因素分析采用Cox比例风险回归模型。结果 Oncomine数据库分析显示,乳腺癌组织中JAG1和Notch3的mRNA水平均高于癌旁组织(P<0.05)。80例乳腺浸润性导管癌组织中JAG1 mRNA水平为1.58±0.56,高于癌旁组织的1.23±0.48(P=0.0039);乳腺浸润性导管癌组织中Notch3 mRNA水平为2.39±0.83,高于癌旁组织的1.95±0.64(P=0.0036)。JAG1和Notch3蛋白在乳腺癌组织中的高表达率为71.3%(57/80)和80.0%(64/80),分别高于癌旁组织的8.8%(7/80)和11.2%(9/80),差异均有统计学意义(P=0.005,P=0.003). JAG1和Notch3蛋白表达在乳腺癌组织中呈正相关(r=0.267,P=0.017)。JAG1和Notch3表达与乳腺癌淋巴结转移、TNM分期和组织学分级有关(P<0.05)。Kaplan-Meier Plotter在线分析显示, JAG1或Notch3高表达的乳腺癌患者的OS短于低表达者(P>0.05)。80例乳腺浸润性导管癌患者中,JAG1高表达者的中位OS为38.3个月,低于JAG1低表达者的80.4个月(P=0.0394);Notch3高表达者的中位OS为39.3个月,低于Notch3低表达者的80.2个月(P=0.0334),且JAG1和Notch3均高表达者的中位OS最短,为27.3个月。Cox多因素分析显示,淋巴结转移、JAG1表达和Notch3表达是影响乳腺癌患者OS的独立因素(P<0.05)。结论 JAG1和Notch3在乳腺癌组织中高表达,且与预后不良有关,有望成为临床评估乳腺癌预后的潜在生物标志物。     

新疆地区局部晚期宫颈癌血清 VEGF-C、D 水平与淋巴结转移及放疗后复发的相关性

目的：探讨新疆地区宫颈癌血清VEGF-C、D亚型水平与淋巴结转移及放疗后复发或淋巴结转移的相关性。方法纳入拟行根治性放化疗的宫颈鳞状细胞癌患者100例,采集血液标本,行根治性放化疗,并进行1年期随访, ELISA法检测血清VEGF-C、D亚型水平,分析治疗前VEGF-C、D与淋巴结转移的相关性,以及治疗后VEGF-C、D与复发或淋巴结转移的相关性。结果治疗前无淋巴结转移58例,一级淋巴结转移31例,二级淋巴结转移11例,血清VEGF-C水平分别为（136．93±68．56）pg／ml,（147．77±76．43）pg／ml,（258．72±98．71）pg／ml,差异有统计学意义（F＝12．45,P＝0．001）;血清VEGF-D分别为（2237．41±472．38）pg／ml,（2163．43±498．26）pg／ml,（2282．31±509．76）pg／ml,差异无统计学意义（F＝0．339,P＝0．71）。治疗后1年随访,患者全部存活,11例出现复发或淋巴结转移,余89例未出现复发或淋巴结转移,2组患者在治疗前血清VEGF-C分别为（251．33±121．39） pg／ml,（141．62±73．31） pg／ml,差异有统计学意义（t＝3．24,P＝0．001）,在治疗后VEGF-C分别为（327．91±73．12） pg／ml,（153．31±49．38） pg／ml,差异有统计学意义（t＝10．45,P＜0．001）;而VEGF-D在治疗前后均无统计学差异。结论血清VEGF-C水平与宫颈癌淋巴结转移明显相关,测定其血清含量有助于宫颈癌治疗前阳性淋巴结的辅助诊断,以及放疗后复发或淋巴结转移的判定。而VEGF-D水平与淋巴结转移无明确关系。     

Levels of Serum 25-Hydroxy-Vitamin D in Benign and Malignant Breast Masses

Background: The true association between breast cancer and vitamin D is currently under investigation.We compared serum 25-hydroxy-vitamin D levels in women with benign and malignant breast masses andcontrols. Materials and Methods: Levels of vitamin D were measured by electrochemiluminescense. Serum levels>35 ng/ml, 25-35 ng/ml, 12.5-25 ng/ml and <12.5 ng/ml were considered as normal, mild, moderate and severevitamin D deficiency, respectively. Results: Overall, 364 women were included in the control, 172 in the benignand 136 in the malignant groups. The median serum vitamin D level was significantly lower in breast cancersthan controls. Levels were also lower in malignant than benign cases and in benign cases than controls althoughstatistically non-significant. Conclusions: Multinomial logistic regression analysis showed that severe vitamin Ddeficiency causes a three-fold increase in the risk of breast cancer while this was not the case for moderate andmild deficiency.     

乳腺癌患者甲状腺功能的相关研究

目的：探讨乳腺癌患者的甲状腺功能情况及与发病间的关系,乳腺癌患者自身免疫与非自身免疫甲状腺疾病的发病情况。方法：收集2008年1月至2013年1月我院诊治的乳腺癌病例100例、乳腺良性疾病患者100例,正常对照病例100例。以放射免疫检测法测血清 FT3、FT4、TSH、TG －Ab、TPO －Ab 水平;通过临床检查、B 型超声、甲状腺素及抗体水平检查、细针穿刺活组织检查等对比甲状腺疾病的发病情况,并分析与乳腺癌的关系。结果：乳腺癌组患者血清 FT4水平（16．56±0．45）pmol／L 和 TPO －Ab 水平（51．44±22．59） U ／ml 虽均在正常范围,但其 FT4水平显著低于乳腺良性疾病组和正常对照组（P ＝0．023,P ＝0．017）,其 TPO－Ab 水平高于乳腺良性疾病组和正常对照组（P ＝0．013,P ＝0．002）。乳腺癌组非自身免疫与自身免疫甲状腺疾病的发病率高于对照组[36％（36／100）vs 12％（12／100）,P ＝0．004;22％（22／100）vs 14％（14／100）, P ＝0．001],乳腺良性疾病组与对照组相近。乳腺癌 FT4降低与乳腺癌的肿块大小、肿瘤分期、淋巴结转移有关联（P ＜0．05）。与年龄、病理类型、ER、PR 表达无关联（P ＞0．05）;乳腺癌 TPO －Ab 高表达与乳腺癌的肿块大小、肿瘤分期、淋巴结转移、ER、PR 表达有关联（P ＜0．05）,与年龄、病理类型无关联（P ＞0．05）。追踪条件匹配的40例乳腺癌放化疗及内分泌治疗,发现与放射肿瘤及内分泌治疗有关联（P ＜0．05）。结论：甲状腺功能变化和乳腺癌的发生发展有一定联系。甲状腺激素和自身抗体水平有助于临床监测和预后判断,乳腺癌患者的非自身免疫与自身免疫甲状腺疾病的发病率高于非乳腺癌者。乳腺癌患者 FT4水平降低及 TPO －Ab 高表达可反映乳腺癌的严重程度。     

Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer.

PURPOSE: The aim of the study was to evaluate the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera samples (s-suPAR) from breast cancer patients. EXPERIMENTAL DESIGN: suPAR levels were determined by the use of a kinetic ELISA in sera from 274 breast cancer patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition, s-suPAR levels were analyzed in 174 female blood donors. RESULTS: The mean s-suPAR level was 3.8 ng/ml (range, 1.6-9.2 ng/ml) in the patients and 3 ng/ml (range, 1.3-6.4 ng/ml) in the donors. The mean c-suPAR level was 0.55 ng/mg protein (range, 0.07-2.83 ng/mg protein). A weak but significant linear association was found between s-suPAR and age in the donors; thus, all of the s-suPAR levels were adjusted for this age dependency (aa-s-suPAR). The aa-s-suPAR levels were significantly increased in the patients as compared with the donors (P < 0.0001). No difference was found in aa-s-suPAR levels between the lymph node-positive and -negative patients (P = 0.27), and no correlation was seen between aa-s-suPAR and c-suPAR (sigma = 0.08; P = 0.71). During the follow-up period (5.9 years) 77 patients experienced a relapse and 69 died. aa-s-suPAR as a continuous variable was significantly associated with relapse-free survival [hazard ratio (HR), 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.003] and overall survival (HR, 1.6; 95% CI, 1.2-2.0; P < 0.0001). In multivariate Cox analysis including the classical prognostic parameters in breast cancer, continuous aa-s-suPAR was significantly associated with both relapse-free survival (HR, 1.4; 95% CI, 1.1-1.7; P = 0.001) and overall survival (HR, 1.4; 95% CI, 1.1-1.8; P = 0.002). In these analyses positive lymph nodes, tumor size >2 cm, and negative estrogen receptor content were also significantly associated with patient outcome. CONCLUSION: This study shows that high preoperative aa-s-suPAR levels are significantly associated with poor outcome for breast cancer patients independent of lymph node status, tumor size, and estrogen receptor status.     

DNA甲基化调控miRNA-328的表达水平与乳腺癌预后的关系分析

目的 探讨DNA甲基化与微小RNA-328（miR-328）表达的关系及miR-328与浸润性乳腺癌临床病理特征和预后的关系。方法 回顾性分析1998年1月至2013年12月从TCGA乳腺癌芯片数据提取的1090例浸润性乳腺癌组织和104例癌旁组织的miR-328表达水平,分析从TCGA_BRCA_hMethyl450芯片数据中获取的775例浸润性乳腺癌组织和98例癌旁组织的miR-328启动子区CpG位点（cg16421621、cg04650403）甲基化率并计算启动子区甲基化与miR-328水平的相关性,从UCSC Genome Browser中的clinical_data_dictionary芯片数据中获取854例有完整临床病理资料及随访数据的乳腺癌标本,分析miR-328表达与临床病理特征及预后的关系,采用Cox回归模型分析影响预后的因素。结果 TCGA数据库1998年1月至2013年12月有miR-328表达量的1194例乳腺癌及癌旁组织中,1090例浸润性乳腺癌组织的miR-328水平为5.224±1.155,低于104例癌旁组织的6.246±0.923,差异有统计学意义（P＜0.01）;775例浸润性乳腺癌组织的miR-328基因启动子区域cg16421621和cg04650403的甲基化率分别为（0.415±0.201）%和（0.193±0.068）%,高于98例癌旁组织的（0.407±0.222）%和（0.094±0.079）%,差异有统计学意义(P＜0.01）;浸润性乳腺癌标本中miR-328的表达量与其启动子区域CG位点（cg16421621、cg04650403）甲基化率呈负相关（r=-0.127, P=0.005）。854例有完整信息的浸润性乳腺癌患者中,miR 328表达水平与淋巴结转移和肿瘤大小有关（P＜0.05）;miR-328低表达组（＜5.462）的中位总生存时间（OS）为7.25年,低于高表达组（≥5.462）的8.75年,差异有统计学意义（P<0.01）。Cox多因素回归分析显示,年龄、淋巴结转移与miR-328表达水平为影响OS的独立因素（P＜0.05）,miR-328高表达组的危险程度低于低表达组（P＜0.01）。结论 浸润性乳腺癌中miR-328表达受其基因启动子区甲基化调控;miRNA-328与浸润性乳腺癌的临床病理特征有关,并能作为影响浸润性乳腺癌预后的危险因素。     

乳腺癌患者血清中sCD44v6检测的临床意义

目的：探讨乳腺癌患者血清中可溶性CD44v6（sCD44v6）蛋白的含量及其临床意义。方法：采用酶联免疫吸附实验（ELISA）检测48例乳腺癌患者手术前后及10例健康对照组血清中sCD44v6蛋白的含量。结果：48例乳腺癌患者血清中sCD44v6蛋白的含量为（546.45±63.79）ng/ml,显著高于健康对照组（167.32±50.06ng/ml,P〈0.01。乳腺癌患者行根治性手术后sCD44 v6蛋白的含量明显下降,有统计学意义,P〈0.05。并与淋巴结转移、组织学分级、TNM分期及低龄（≤35岁）密切相关。结论：sCD44v6水平可作为诊断、治疗乳腺癌及预测乳腺癌患者转移复发风险及预后的辅助指标。     

Angiogenic characteristics of circulating and tumoural thrombospondin-1 in breast cancer

In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote metastasis by increasing adhesion of malignant cells to endothelium. To determine the role of TSP-1 in breast cancer and breast cancer angiogenesis, we have measured TSP-1 in plasma and tumour cytosols and compared levels to established clinicopathological prognostic parameters and intratumoural microvessel density. TSP-1 was measured, by radioimmunoassay, in plasma (pTSP-1) and tumour cytosols (cTSP-1) of women with early breast cancer (EBC) (n=71). pTSP-1 in EBC was compared to pTSP-1 levels in women with advanced breast cancer (ABC) (n=66), normal controls (n=77) and was correlated with prognostic features and microvessel density (MVD) (measured by CD31 immunostaining). cTSP-1 levels were compared to prognostic features and microvessel density. pTSP-1 in women with EBC (median 484, IQR 344-877 ng/ml) and ABC (median 588, IQR 430-952 ng/ml) were elevated when compared to normal controls (median 21, IQR 175-247) (p<0.001). Women with lymph node metastases (n=35) had higher levels of TSP-1 (median 799 ng/ml, IQR 455-943) than women who were node negative (median 343 ng/ml, IQR 267-514) (n=36) (p<0.05). Levels of pTSP-1 in EBC correlated with MVD (R=0.39, p<0.05). Levels of TSP-1 in tumour cytosols of women with EBC (median 1714, IQR 893-5283 ng/ml) correlated with microvessel density (R=0.46, p<0.01). Circulating levels of TSP-1 appear to be a marker of breast cancer aggressiveness and in breast cancer may have a pro-angiogenic rather than anti-angiogenic role.     

Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis.

The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.     

Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency

We correlated serum 25-hydroxyvitamin D(3) (25OHD) levels with tumor characteristics and clinical disease outcome in breast cancer patients and assessed the impact of genetic determinants of vitamin D insufficiency. We collected serum from 1800 early breast cancer patients at diagnosis, measured 25OHD by radioimmunoassay (RIA), and determined genetic variants in vitamin D-related genes by Sequenom. Multivariable regression models were used to correlate 25OHD levels with tumor characteristics. Cox proportional hazard models were used to assess overall survival (OS), disease-specific survival (DSS), and disease-free interval (DFI). Lower 25OHD serum levels significantly correlated with larger tumor size at diagnosis (P = 0.0063) but not with lymph node invasion, receptor status, or tumor grade. Genetic variants in 25-hydroxylase (CYP2R1) and vitamin D-binding (DBP) protein significantly determined serum 25OHD levels but did not affect the observed association between serum 25OHD and tumor size. High serum 25OHD (>30 ng/mL) at diagnosis significantly correlated with improved OS (P = 0.0101) and DSS (P = 0.0192) and additionally had a modest effect on DFI, which only became apparent after at least 3 years of follow-up. When considering menopausal status, serum 25OHD had a strong impact on breast cancer-specific outcome in postmenopausal patients [hazards ratios for 25OHD >30 ng/mL versus ≤30 ng/mL were 0.15 (P = 0.0097) and 0.43 (P = 0.0172) for DSS and DFI, respectively], whereas no association could be demonstrated in premenopausal patients. In conclusion, high vitamin D levels at early breast cancer diagnosis correlate with lower tumor size and better OS, and improve breast cancer-specific outcome, especially in postmenopausal patients.     

前列腺癌患者血清睾酮水平、前列腺雄激素受体表达与精索静脉曲张相关研究

目的：研究血清睾酮水平、前列腺雄激素受体（AR）表达与精索静脉曲张的相关性,为临床前列腺疾病诊治提供一定理论依据。方法选取未经药物治疗的64例前列腺癌患者,其中实验组为32例前列腺癌合并精索静脉曲张患者,对照组为32例前列腺癌不伴精索静脉曲张患者,记录两组患者一般情况,并行血清睾酮水平、前列腺雄激素受体检测及病理组织学检查。结果对照组血清睾酮水平为（5.89±1.32）ng/ml,实验组血清睾酮值为（6.07±1.16）ng/ml,差异无统计学意义（P﹥0.05）。实验组前列腺雄激素受体的阳性表达率为62.5%,低于对照组84.4%,差异有统计学意义（P﹤0.05）。AR的表达均与伴精索静脉曲张前列腺癌分期呈负相关（r=-0.318, P﹤0.05）。结论前列腺雄激素受体表达在前列腺癌精索静脉曲张的发病及病情进展中发挥了重要的作用。     

Role of Vitamin D Deficiency and Lack of Sun Exposure in the Incidence of Premenopausal Breast Cancer: a Case Control Study in Sabzevar,Iran

Background: Vitamin D has been suggested as one of the critical factors for female reproductive health withprotective activities against different cancers but there are conflicting facts regarding its role on breast cancerwithout any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietarysources and sunlight exposure on the incidence of premenopausal breast cancer. Materials and Methods: Weconducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normalwomen who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area ofIran. Results: The mean concentrations of 25-OH vitamin D in cases and controls were 15.2±8.15 vs 15.5±7/45ng/ml, both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe orsevere vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitaminD and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115,CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232,CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack ofsunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131,CI 98% 0.314-78.102). Conclusion: This study pointed out the role of vitamin D and other possible risk factorson the development and growth of breast tumors in this special geographical region. Although this study hasrevealed the interactions between hormonal and environmental factors in this province of Iran, understandingthe deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary.     

RNA甲基转移酶BCDIN3D的表达与乳腺癌预后的关系

目的探讨RNA甲基转移酶BCDIN3D的表达与乳腺癌患者预后的关系。方法选取2013年6月至2015年1月重庆市红十字会医院收治的乳腺癌患者80例,年龄19～65(467±47)岁;分子分型Luminal A、Luminal B、ERBB2+、Basal like型分别10、32、20、18例;肿瘤分期T0～1、T2、T3分别9、34、37例;淋巴结分期N0～1、N2、N3分别9、38、33例。均行标准乳腺癌改良根治术,术中获取乳腺癌组织标本,采用免疫组织化学法(IHC)检测乳腺癌组织中BCDIN3D的表达情况。对患者进行随访,统计总生存期(OS)。采用COX比例风险模型分析乳腺癌患者预后的影响因素。结果80例乳腺癌患者中,BCDIN3D阳性表达者30例(375％);BCDIN3D阴性表达者50例(625％)。BCDIN3D阳性表达者与BCDIN3D阴性表达者间肿瘤分期和淋巴结分期差异有统计学意义(P<005),不同年龄、月经状态、分子分型差异均无统计学意义(P>005)。中位随访时间为42(23～64)个月,Kaplan Meier分析结果显示,BCDIN3D阳性表达者、BCDIN3D阴性表达者的中位OS分别为412(95％CI:312～469)、495(95％CI:421～516)个月,BCDIN3D阳性表达者的OS短于BCDIN3D阴性表达者(χ2=25241,P<0001)。COX分析结果显示,肿瘤分期、淋巴结分期、分子分型、BCDIN3D表达是影响乳腺癌患者OS的独立预后因素(P<005)。结论BCDIN3D阳性表达与乳腺癌患者预后不良有关。     

Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR

The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration 相似文献   

Extracellular matrix building marked by the N-terminal propeptide of procollagen type I reflect aggressiveness of recurrent breast cancer

The purpose of our study was to examine the association between extracellular matrix homeostasis and aggressive breast cancer as reflected by the synthesis of type I collagen marked by circulating concentration of the aminoterminal propeptide of type I procollagen (PINP). Pre-therapeutic serum PINP concentrations were measured in 154 healthy women and 100 patients referred with their first metastatic manifestation of breast cancer and correlated to the metastatic pattern, response to therapy, time to progression and survival with a minimal follow-up of 5 years. Fifty-four percent of the patients had serum PINP concentrations greater than the 95th percentile of the healthy controls and 38% were high PINP level patients with values clearly outside normal range (>125 ng/ml). Patients with high PINP levels were more sick (p = 0.002), had a higher tumor burden (p = 0.013) and revealed a lower responsiveness to anthracycline-based therapy (p = 0.0002) as well as an accelerated time to disease progression (p = 0.00001) and death (p = 0.0006). Median survival in the high serum PINP level group was less than half of that in the group with low PINP level (14.5 vs. 32 months). The lowest PINP levels were seen when the cancer was restricted to the lymph node and skin and increasing PINP levels were found if the cancer had spread to the lungs, the bones, the bone marrow and the liver. High PINP level at recurrence and lack of estrogen receptors (ER) independently reflected aggressive tumor behavior after recurrence with an equal great impact on time to progression and survival. Patients with a high PINP level and primarily ER-negative tumors survived a median of only 6 months with no one alive after 22 months. By contrast patients with a low PINP level and ER-positive tumors had a median survival of 37 months and 23% were still alive after 5 years. Aggressive breast cancer induces a strong fibroproliferative response with synthesis of type I collagen. Serum PINP levels may be a diagnostic and prognostic tool that indicate breast cancer activity, aggressiveness, expansion and metastasis and a predictor of outcome after anthracycline-based chemotherapy.     

ＫＬ-６粘蛋白在乳腺肿瘤中的测定及其临床意义

目的　探讨ＫＬ-６粘蛋白在乳腺肿瘤患者血浆和肿瘤组织中的表达,并分析其与临床病理指标及ＥＲ、ＰＲ、ＨＥＲ-２的关系。方法　采用ＥＬＩＳＡ法检测乳腺肿瘤患者与健康对照组血浆ＫＬ-６水平,并用免疫组化方法定位检测组织ＫＬ-６粘蛋白的表达情况。结果　乳腺癌组血浆ＫＬ-６水平为（４.１９１±３.５９８）ｎｇ／ｍｌ,明显高于健康对照组的（１.７０２±０.７３７）ｎｇ／ｍｌ和乳腺纤维腺瘤组的（１.７７５±０.６５３）ｎｇ／ｍｌ,差异有统计学意义（Ｐ＝０.０００）。乳腺癌患者血浆ＫＬ-６表达与肿瘤分化程度、肿瘤大小、淋巴结转移及分期等密切相关,与年龄、月经状况、ＥＲ、ＰＲ及ＨＥＲ-２等无关;乳腺癌组织ＫＬ-６表达与肿瘤分化程度、肿瘤大小、淋巴结转移和分期等密切相关,与年龄、月经状况、ＥＲ、ＰＲ及ＨＥＲ-２等无关。结论　ＫＬ-６在乳腺癌血浆及组织中表达均增高,并与肿瘤分化程度、肿瘤大小、淋巴结转移、分期等密切相关,有可能作为筛查、预后判断及基因靶向治疗的标记物。