Variations in the Concentrations of Cu and Zn and in the Ratio of Cu to Zn in Whole Blood and Hair Samples from Hepatocellular Carcinoma Patients and from Healthy Controls in Taiwan

An atomic absorption spectrophotometer was used to determine concentrations of copper and zinc and the ratio of Cu to Zn in samples of whole blood and hair from hepatocellular carcinoma (HCC) patients (n=51) and from healthy controls (n=50) in Taiwan. Our results indicate that the HCC patients have higher copper concentrations and higher ratios of Cu to Zn than do the healthy controls both in whole blood and hair samples, but only the concentration of copper and the ratio of Cu to Zn in whole blood were significantly different (p<0.001 and p<0.05). Conversely, a lower concentration of zinc was found in whole blood and hair samples of HCC patients. Similarly, only the concentration of zinc in whole blood showed a significant difference (p<0.001). We concluded that the whole blood concentrations of copper and zinc and the ratio of Cu to Zn seemed to have a higher correlation with HCC. Thus, we suggest that a sample of whole blood may be a more suitable diagnostic sample than is a hair sample for HCC.     

胃癌危险因素病例对照研究

报告了在南昌市进行的一项胃癌危险因素的病例对照研究，共调查胃癌病人39例和对照134例，经单因素分析，发现主要危险因素为吸烟，饮烈性酒，进食快，食辛辣食物，腌菜，精神受刺激，好生闷气，胃溃疡史等，而进食规律。多吃水果则具保护作用，同时对病例和对照做了血清微量元素测定，表明胃癌患者血清中Mo、Se和Zn缺乏与胃癌的发生有关。     

Modelling the Recurrence of Bladder Cancer

The risk of a new tumor recurrence after transurethral resection (surgical operation) in patients with primary superficial bladder carcinoma is evaluated. As the exact time of the event is not known, it is suggested to consider interval-censored survival data methodology. We use the model of Farrington to perform a prognostic model for predicting a new recurrence and to determine the clinicopathologic factors associated within interval-censored data framework. The implementation of this method is easy using standard statistical packages. Anyway, we use diagnostic methods for the validation of the model developed by the same author for interval-censored data. The obtained model is easily interpretable and let us to individualize the course of follow-up and treatment of each patient in order to improve the patient’s quality of life.      

Using Gd-EOB-DTPA-enhanced 3-T MRI for the differentiation of infiltrative hepatocellular carcinoma and focal confluent fibrosis in liver cirrhosis

Purpose

The purpose of the study was to determine significant imaging features to differentiate between infiltrative hepatocellular carcinoma (HCC) and confluent fibrosis (CF) in liver cirrhosis using Gd-EOB-DTPA-enhanced 3-T magnetic resonance imaging.

Material and methods

Nineteen infiltrative HCCs and eight CFs were included. We evaluated the difference in imaging findings and apparent diffusion coefficient (ADC) between the two entities. We compared T2-weighted image (WI) and hepatobiliary phase (HBP) in terms of the clarity of the lesion outer margin.

Results

Seventeen infiltrative HCCs showed lobulated margin, while focal CFs showed either straight (n = 3) or irregular margins (n = 5) (P = .001). All infiltrative HCCs had intact or bulging contours, and all focal CFs showed capsular retraction (P = .001). Fourteen infiltrative HCCs and two focal CFs showed arterial enhancement (P = .035). The ADC of infiltrative HCCs was significantly lower than that of CFs (P = .001). Satellite nodules were noted in 10 infiltrative HCCs. In terms of outer margin clarity, infiltrative HCCs showed a more distinct margin on HBP than on T2-WI (P = .005), while these two sequences were not significantly different in focal CFs (P = 1.000).

Conclusion

HBP improved the imaging characteristics of infiltrative HCC, allowing it to be distinguished from focal CF. Infiltrative HCC showed lower ADC values than focal CF. Lobular configuration, contour bulging, enhancement pattern, associated satellite nodules and portal vein thrombosis were still found to be highly suggestive MR findings for infiltrative HCC.     

Magnetic resonance imaging of mouse Ehrlich carcinoma growth inhibition by thiacarpine, an analogue of cytotoxic marine alkaloid polycarpine

The anticancer effect of thiacarpine, a synthetic analogue of the known cytotoxic alkaloid polycarpine isolated from the Pacific ascidian Polycarpa aurata, was investigated in vivo in experiments using mouse solid Ehrlich carcinoma tumor as the target. A high-resolution magnetic resonance imaging (MRI) technique using a MR tomograph "PharmaScan" US70/16 (Bruker, Ettlingen, Germany) was used for visualization and quantification of tumor size. Fluorescence microscopy and image analysis were applied to determine Ehrlich carcinoma cell chromatin condensing (apoptosis) and necrosis in Ehrlich carcinoma cells at the action of thiacarpine in in vitro experiments. The scan and size calculations of the tumor and some mouse organs were carried out during the experiments. Thiacarpine in a total dose of 100 mg/kg was found to exhibit the delay in growth of the mouse tumor. The antineoplastic effect of this compound was accompanied by an increase in the lifetime of experimental mice in comparison with the control group of animals. Our data show that the ability of thiacarpine to induce apoptosis in carcinoma cells may contribute to thiacarpine anticancer effects against mice solid Ehrlich carcinoma in vivo detected by MRI.     

UPLC‐MS/MS based diagnostics for epithelial ovarian cancer using fully sialylated C4‐binding protein

Serum levels of fully sialylated C4‐binding protein (FS‐C4BP) are remarkably elevated in patients with epithelial ovarian cancer (EOC) and can be used as a marker to distinguish ovarian clear cell carcinoma from endometrioma. This study aimed to develop a stable, robust and reliable liquid chromatography–hybrid mass spectrometry (UPLC‐MS/MS) based diagnostic method that would generalize FS‐C4BP as a clinical EOC biomarker. Glycopeptides derived from 20 μL of trypsin‐digested serum glycoprotein were analyzed via UPLC equipped with an electrospray ionization time‐of‐flight mass spectrometer. This UPLC‐MS/MS‐based diagnostic method was optimized for FS‐C4BP and validated using sera from 119 patients with EOC and 127 women without cancer. A1958 (C4BP peptide with two fully sialylated biantennary glycans) was selected as a marker of FS‐C4BP because its level in serum was highest among FS‐C4BP family members. Preparation and UPLC‐MS/MS were optimized for A1958, and performance and robustness were significantly improved relative to our previous method. An area under the curve analysis of the FS‐C4BP index receiver operating characteristic curve revealed that the ratio between A1958 and A1813 (C4BP peptide with two partially sialylated biantennary glycans) reached 85%. A combination of the FS‐C4BP index and carbohydrate antigen‐125 levels further enhanced the sensitivity and specificity.     

Synthesis and antiproliferative evaluation of oxime,methyloxime, and amide‐containing quinazolinones

Certain oxime, methyloxime, and amide‐containing quinazolinone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal carcinoma (NPC‐TW01), lung carcinoma (NCI‐H226), and leukemia (Jurkat). Quinazolinone 2 was inactive against all three cell lines tested, while quinazolinone 4 was weakly active against both Jurkat and H226 cancer cells with IC₅₀ values of 6.55 and 12.27 μM, respectively, indicating that the oxime derivative 4 is more favorable than its ketone precursor 2 . Our results have also indicated that quinazolinone 8g and its biphenyl counterpart 8f exhibited more potent antiproliferative activities than the positive control methotrexate against all three cancer cell lines tested. Among these quinazolinone derivatives, 8g was the most active against NPC‐TW01 with an IC₅₀ value of 4.78 μM. Further study on NPC‐TW01 cell cycle distribution indicated that the compound 8g induced cell arrest at the G1/G0 phase in a time‐ and concentration‐dependent manner. Moreover, a characteristic hypo‐diploid DNA content peak (sub‐G1) was found to increase from 1 to 4% in NPC‐TW01 cells treated with 8g for 72 hr. These results indicate that 8g can induce cells arrest in the G1/G0 phase and cause cell death. Further structural optimization of 8g and detailed study of its antiproliferative mechanism are going on.     

C(4)取代紫杉醇类似物的定量构效关系研究

用量子化学B3LYP／6-31G方法计算了23个C（4）取代紫杉醇类似物的结构,用遗传算法（GFA）对能量、电性、拓扑及热力学等类型的278个结构描述符进行筛选,并回归建立其抑制人体结肠癌细胞HCT-116活性的定量构效关系（QSAR）．QSAR方程含分子体积Vm、分子分支度指数CHI-O、分子中带正电荷原子的溶剂可积面积与其所带电荷之积的加和值Jurs-PPSA-3以及分子表面积S4个结构描述符．方程的拟合相关系数的平方R^0及交叉验证系数Q^2分别为0．956和0．913,所得QSAR具有可信的预报能力．由优化后的几何构型知,C（4）取代基、C（13）侧链和2-OBz三基团共同形成疏水腔,C（4）取代基的改变影响C（13）侧链的电子结构．C（13）连接的18号O原子的负电荷越大、3’位连接的NHBz基团的极性越小活性越高;C（4）取代基若为吸电子基对活性不利;适当增大分子体积、表面积和疏水性,保持一定的分支度对活性有利．     

Proteomic approach for purification of seminal plasma proteins involved in tumor proliferation

Human seminal plasma contains a large array of proteins required for the normal physiology and metabolism of spermatozoa. These are mainly secreted from prostate epithelium, testes, and seminal vesicles. Fortunately, many of these are found to be present at elevated concentration in seminal plasma and act as a biomarker of different carcinomas as their levels are also enhanced in serum and are found to be involved in tumor progression and metastasis apart from fertility. The proteins which were overexpressed in the seminal plasma of prostate carcinoma patients were identified by 2-DE and MALDI-TOF/MS. We have designed a strategy to purify these four proteins prostate specific antigen (PSA), prostatic acid phosphatase (PAP), Zinc alpha2-glycoprotein (ZAG), and progastricsin (PG), together in homogeneity by using simple chromatographic techniques. Acidic and basic fractions of human seminal plasma were separated by ion exchange chromatography and further purified by gel permeation chromatography. Our results form a new and valuable resource for those attempting structure-based drug designing for prostate and other cancers where the amount of proteins is required in plenty and in native form.     

Identification of human hepatocellular carcinoma-related proteins by proteomic approaches

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. Analysis of human serum from HCC patients using two-dimensional gel electrophoresis (2DE) combined with nano-high-performance liquid chromatography electrospray ionization tandem mass spectrometry (nano-HPLC–ESI-MS/MS) identified fourteen different proteins differentially expressed between HCC patients and the control group. Twelve proteins were up-regulated and two down-regulated. By using nano-HPLC–MS/MS system to analyze proteome in human serum, 317 proteins were identified, twenty-nine of which to high confidence levels (protein matched at last two unique peptide sequences). Of these twenty-nine proteins, six were present only in HCC patients and may serve as biomarkers for HCC. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.