Ascorbic acid analogue 6-Deoxy-6-[18F] fluoro-L-ascorbic acid as a tracer for identifying human colorectal cancer with SVCT2 overexpression

L-ascorbic acid (AA) was reported to have an anti-cancer effect over 40 years. In recent years, several ongoing clinical trials are exploring the safety and efficacy of intravenous high-dose AA for cancer treatment. The lack of appropriate imaging modality limits the identification of potentially suitable patients for AA treatment. This study focuses on identifying AA-sensitive tumor cells using molecular imaging. 6-Deoxy-6-[¹⁸F] fluoro-L-ascorbic Acid (¹⁸F-DFA), a structural analog of AA, was synthesized and labeled to visualize the metabolism of AA in vivo. Colorectal cancer (CRC) cell lines with high and low expression of sodium-dependent vitamin C transporters 2 (SVCT2) were used for a series of cellular uptake tests. PET imaging was performed on xenograft tumor-bearing mice. More AA uptake was observed in CRC cells with high SVCT2 expression than in cells with low SVCT2 expression. The substrate (unlabeled AA) can competitively inhibit the ¹⁸F-DFA tracer uptake by CRC cells. The biodistribution of ¹⁸F-DFA in mice showed high radioactivity was seen in organs such as adrenal glands, kidneys, and liver that were known to have high concentrations of AA. Both PET imaging and tissue distribution showed that cancer cells with high SVCT2 expression enhanced the accumulation of ¹⁸F-DFA in mice after tumor formation. Immunohistochemistry was used to verify the corresponding results. As a radiotracer, ¹⁸F-DFA can provide powerful imaging information to identify tumor with high affinity of AA, and SVCT2 can be a potential biomarker in this process.     

The proliferation of colorectal cancer cells is suppressed by silencing of EIF3H

Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Eukaryotic translation initiation factor 3, subunit H (EIF3H) is a subunit of EIF3, which is involved in mRNA recruitment and ribosomal complex disassembly and is known to be a driver of cell proliferation and survival in cancer. To investigate its function in colorectal cancer, the Oncomine database was used to evaluate the expression of EIF3H in human colorectal cancer and normal tissues. Then, we constructed a Lentivirus shorthair EIF3H vector (Lv-shEIF3H) to silence EIF3H expression in the colorectal cancer cell lines HCT116 and SW1116. We observed impaired cell growth and colony formation in these silenced cell lines. In addition, we showed that EIF3H knock-down led to cell apoptosis. In conclusion, EIF3H plays key roles in the apoptosis in colorectal cancer cells, which suggests EIF3H as a potential diagnostic biomarker in colorectal cancer.     

MicroRNA–mRNA interaction network using TSK-type recurrent neural fuzzy network

MicroRNAs are short non-coding RNAs that can regulate gene expression during various crucial cell processes such as differentiation, proliferation and apoptosis. Changes in expression profiles of miRNA play an important role in the development of many cancers, including CRC. Therefore, the identification of cancer related miRNAs and their target genes are important for cancer biology research. In this paper, we applied TSK-type recurrent neural fuzzy network (TRNFN) to infer miRNA–mRNA association network from paired miRNA, mRNA expression profiles of CRC patients. We demonstrated that the method we proposed achieved good performance in recovering known experimentally verified miRNA–mRNA associations. Moreover, our approach proved successful in identifying 17 validated cancer miRNAs which are directly involved in the CRC related pathways. Targeting such miRNAs may help not only to prevent the recurrence of disease but also to control the growth of advanced metastatic tumors. Our regulatory modules provide valuable insights into the pathogenesis of cancer.     

In situ quantification of aberrant p53 in colorectal neoplasia

Aberrant p53 protein accumulation was measured immunohistologically in 342 colorectal paraffin-embedded tissue sections from 115 patients (24 with adenocarcinoma, 59 with adenoma and 32 'hospital controls'). Subjective scoring was compared with quantitative cell imaging, including dichotomous (p53⁺/p53^?) status, ng p53^mut mg^?1 enterocyte protein, and tumour burden and patient body 'burden' of aberrant p53. A total of 62.5% cancer patients, 23.7% adenoma patients and 3.1% hospital controls were accorded p53⁺ status on the basis of p53 quantification. Quantitative p53⁺/p53^? assignment had a stronger inverse association with survival (χ²=6.17, p=0.013, Kaplan-Meier test) than subjective 'visual estimation' (χ²=0.57, p=0.449). There was a strong inverse relationship between the p53 'body burden' and the months of post-diagnosis survival (hazard ratio=1.42, p=0.0004, Cox proportional hazards). Absolute quantification for inactivated p53 permits objective and reproducible scoring, adjusts for intra-laboratory immunostaining 'batch effects', corrects for fixation artefacts, and standardizes for inter-laboratory differences in fixation, antibody selection and staining method. Clinically, in situ quantification of p53 will permit more accurate survival prognoses and will inform therapy selection and dose. Ultimately, accurate quantitative tissue/blood p53 correlations may provide a minimally invasive and systemic surrogate measure for these same clinical purposes.     

窄带成像内镜、染色内镜及常规内镜模式诊断结直肠增生性病变的应用价值比较研究

目的:探讨窄带成像内镜(NBI)、染色内镜及常规内镜模式鉴别诊断非肿瘤性、肿瘤性结直肠增生性病变的应用价值。方法:选择2017年2月至2019年3月西安市中心医院消化科收治的结直肠增生性病变患者,均行NBI、染色内镜、常规内镜检查。比较三种模式图像清晰度以及鉴别诊断非肿瘤性、肿瘤性结直肠增生性病变的效能。结果:NBI、染色内镜模式图像质量评分分布优于常规内镜(P<0.05),NBI图像质量评分分布优于染色内镜模式(P<0.05)。以病理结果为准,常规内镜结直肠增生性病变检出率73.13%,NBI 91.04%,染色内镜96.26%,NBI、染色内镜结直肠增生性病变检出率高于常规内镜(P<0.05),NBI、染色内镜比较无统计学差异(P>0.05)。NBI模式下检测NBI分型与病理组织学结果一致性较好(kappa值=0.801,P<0.05)。NBI、染色内镜诊断肿瘤性结直肠增生性病变的灵敏度、特异度、阳性预测值、阴性预测值、准确度均明显高于常规内镜,染色内镜、NBI、常规内镜诊断肿瘤性结直肠增生性病变的曲线下面积(AUC)分别为0.844(95%CI:0.812~0.956)、0.921(95%CI:0.860~0.982)、0.750(95%CI:0.651~0.848)。结论:NBI、染色内镜在鉴别非肿瘤性和肿瘤性结直肠增生性病变方面效能相似,均优于常规内镜,NBI分型与病理组织学结果一致性高,更适合结直肠增生性病变的鉴别诊断。     

Breast and colorectal cancer recurrence-free survival estimates in the US: Modeling versus active data collection

BackgroundA modeling method was developed to estimate recurrence-free survival using cancer registry survival data. This study aims to validate the modeled recurrence-free survival against “gold-standard” estimates from data collected by the National Program of Cancer Registries (NPCR) Patient-Centered Outcomes Research (PCOR) project.MethodsWe compared 5-year metastatic recurrence-free survival using modeling and empirical estimates from the PCOR project that collected disease-free status, tumor progression and recurrence for colorectal and female breast cancer cases diagnosed in 2011 in 5 U.S. state registries. To estimate empirical recurrence-free survival, we developed an algorithm that combined disease-free, recurrence, progression, and date information from NPCR-PCOR data. We applied the modeling method to relative survival for patients diagnosed with female breast and colorectal cancer in 2000–2015 in the SEER-18 areas.ResultsWhen grouping patients with stages I-III, the 5-year metastatic recurrence-free modeled and NPCR-PCOR estimates are very similar being respectively, 90.2 % and 88.6 % for female breast cancer, 74.6 % and 75.3 % for colon cancer, and 68.8 % and 68.5 % for rectum cancer. In general, the 5-year recurrence-free NPCR-PCOR and modeled estimates are still similar when controlling by stage. The modeled estimates, however, are not as accurate for recurrence-free survival in years 1–3 from diagnosis.ConclusionsThe alignment between NPCR-PCOR and modeled estimates supports their validity and provides robust population-based estimates of 5-year metastatic recurrence-free survival for female breast, colon, and rectum cancers. The modeling approach can in principle be extended to other cancer sites to provide provisional population-based estimates of 5-year recurrence free survival.     

Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia

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