A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q_values) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log₂‐transformed multivariable models, equol (odds ratio [OR] per log₂‐value, 0.86, 95% confidence interval [95% CI] = 0.79–0.93; q_value = 0.01) and homovanillic acid (OR per log₂‐value, 1.46, 95% CI = 1.16–1.84; q_value = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41–0.91, p_trend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17–2.53, p_trend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.     

Prognostic value of intra‐tumoral CD8+/FoxP3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis

Background and Objectives

Patients with isolated colorectal‐cancer‐liver‐metastases (CRCLM) frequently undergo metastatectomy. Tumor‐infiltrating‐lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor‐infiltrating CD8⁺ cytotoxic T‐cells and FoxP3⁺ regulatory T‐cells at the metastatic site of CRCLM patients.

Methods

TILs were isolated from fresh metastatic tissues of 47 patients with CRCLM. Archived paraffin‐embedded tissue, from the same patients, was retrieved. CD8⁺ and FoxP3⁺ cells, both in the intra‐tumoral and the peri‐tumoral compartments, were measured by immunohistochemistry on full tissue sections. Proportions of cytotoxic T‐cells (CD8⁺) and regulatory T‐cells (CD4⁺CD25⁺FoxP3⁺), within CD45⁺TILs, were measured by flow‐cytometry.

Results

By immunohistochemistry, individual densities of intra‐tumoral or peri‐tumoral CD8⁺ and FoxP3⁺ cells were not prognostic of survival. However, the intra‐tumoral, but not the peri‐tumoral, CD8⁺/FoxP3⁺ ratio was an independent predictor of survival (HR 0.43, 95%CI 0.19‐0.95, P = 0.032). By flow cytometry, the intra‐tumoral CD8⁺/regulatory T‐cell ratio was also an independent predictor of survival (HR 0.45, 95%CI 0.20‐0.99, P = 0.044).

Conclusions

The ratio of cytotoxic (CD8⁺) to regulatory (FoxP3⁺) T‐cells, in the intra‐tumoral compartment, but not in the peri‐tumoral compartment, can predict survival after resection of CRCLM.     

Urokinase Plasminogen Activator Receptor (uPAR): A Potential Indicator of Invasion for In Situ Breast Cancer

Abstract: Urokinase plasminogen activator (uPA) and its cellular receptor (uPAR) are important mediators in the cellular process of cancer invasion and metastasis. Ductal carcinoma in situ (DCIS) is classified by lack of invasion into the adjacent stroma, yet definitive histologic features have not been identified to indicate the propensity for cellular invasion. Therapy for DCIS remains controversial because of the probability for recurrence. We hypothesized that uPA and uPAR may represent new predictors for recurrence of DCIS. Tissue specimens were obtained from 10 normal, 10 hyperplasia, and 70 patients with DCIS. Representative sections of the regions were mounted and stained by immunohistologic techniques using mouse anti-human uPA and uPAR antibodies. Stain intensities were assessed by densitometry image analysis. Gray scale values for in situ patients were compared to normal averages to determine whether staining intensities were normal or significantly higher (p < 0.05) than normal. DCIS tissues were heterogeneous for stain intensities of uPA and uPAR. Patients with high stain intensities for uPAR (28/70 = 40%) correlated with a higher recurrence rate (15/28 = 54%) than with patients having high stains for uPA (19/70 = 28% with 17/50 = 34% recurrence). In addition, patients with combined high stains for uPA and uPAR (11/19 = 60%) showed a recurrence rate of 55% compared to high uPA/normal uPAR with 0% recurrence. Immunohistologic evaluation of DCIS for uPAR, alone and in combination with uPA, significantly correlates with recurrence of invasive breast carcinoma. Evaluation of uPAR among DCIS lesions may provide a new prognostic indicator for recurrence of breast carcinoma.     

Incorporation of the biomarker concept in ecotoxicology calls for a redefinition of terms

Biomarkers have received a lot of attention but the biomarker concept has not yet been defined properly. As a consequence, various interpretations of the term biomarker exist, some of which overlap with well-established ecotoxicological concepts. To allow incorporation of the biomarker concept within the framework of modern ecotoxicology, a clarification of terms is needed. In this paper, definitions are presented for the terms biomarker, bioindicator and ecological indicator, which do not overlap and are linked to different levels of biological organization. The use of these concepts for ecological effects assessment is discussed.     

基于GC-MS代谢组学的RSV肺炎小鼠尿液和粪便生物标记物研究

目的?通过气相色谱-质谱联用（GC-MS）技术分析RSV肺炎小鼠尿液和粪便中代谢物的相对含量变化,寻找可协助RSV肺炎诊断的生物标记物。方法?RSV滴鼻感染BALB/c小鼠建立RSV肺炎模型,分别收集小鼠的尿液和粪便,经肟化和衍生化后,运用GC-MS检测尿液和粪便中所含有的代谢物及其相对含量的变化。结果?RSV肺炎小鼠的尿液中共测得38种代谢产物,其中乳酸、丙酸、L-脯氨酸为差异代谢产物（P<0.05）;粪便中共测得43种代谢物,其中亮氨酸、天冬氨酸、胱氨酸、酪氨酸、嘧啶有显著差异（P<0.05）。结论?运用GC-MS代谢组学技术寻找RSV肺炎小鼠尿液和粪便中的生物标记物具有可行性。      

急性冠脉综合征患者血浆miR-15b、miR-92a水平及其意义

目的探讨急性冠脉综合征患者血浆miR-15b、miR-92a的表达情况及其与冠脉病变严重程度的相关性方法收集138例研究对象,其中冠脉正常组44例,不稳定型心绞痛组(UA)44例,急性ST段抬高型心肌梗死组(STEMI)50例,应用RT-q PCR技术测定三组空腹血浆中miR-15b、miR-92a的表达水平,同时统计三组一般临床资料及生化指标。比较三组间生化指标、miRNAs水平的差异及miRNAs水平与冠脉SYNTAX评分的相关性。结果血浆miR-15b表达水平在STEMI组、UA组比冠脉正常组明显下降(P0.01)。血浆miR-92a水平在STEMI组、UA组比冠脉正常组明显升高(P0.01),同时,STEMI组miR-92a表达水平比UA组升高更显著(P0.05)。STEMI组血浆miR-92a与SYNTAX评分呈正相关,相关系数r=0.779(P0.01);UA组血浆miR-92a与SYNTAX评分呈正相关,相关系数r=0.828(P0.01)结论 UA、STEMI患者血浆中miR-15b表达水平降低,而miR-92a表达水平升高,血浆miR-92a表达水平与急性冠脉综合征患者冠脉病变严重程度相关。     

循环肿瘤细胞检测与临床应用进展

循环肿瘤细胞是指自发或因诊疗操作脱离实体瘤原发灶或转移灶而进入外周血循环的肿瘤细胞,其已被研究证实是包括乳腺癌、肺癌、胰腺癌、结直肠癌等在内的多种癌症的诊断和预后标志物,有助于肿瘤的体外早期诊断、耐药性监测,判断预后及生存分析,检测肿瘤复发、评价药物疗效以辅助治疗决策及调整治疗方案.但目前循环肿瘤细胞的检测方法仍存在一定的局限性,研究出具有更高灵敏度和特异性的检测新方法将有助于循环肿瘤细胞在临床上的应用.本文将从循环肿瘤细胞的检测技术、临床应用以及临床应用展望等方面对循环肿瘤细胞检测的研究进展和临床应用作一简述.     

Evolving utility of exosomes in pancreatic cancer management

Despite the development of newer oncological treatment, the survival of patients with pancreatic cancer (PC) remains poor. Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation, metastasis and chemoresistance. Thus, the utility of liquid biopsies using exosomes in PC management can be used for early detection, diagnosis, monitoring as well as drug delivery vehicles for cancer therapy. This review summarizes the function, and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic, prognostic and therapeutic roles.