Interventional Radionuclide Therapy of Hepatocellular Carcinoma:Assessment of Intratumoral Retention of HPMA Copolymers

To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly(HPMA)-APMA-DTPA[HPMA=N-(2-hydroxypropyl) methacrylamide; APMA=N-(3-aminopro-pyl)methacrylamide; DTPA=diethylenetriaminepentaacetic acid] was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N′-azobis(isobutyronitrile) as the initiator. The copolymers were characterized with nuclear magnetic resonance(NMR) spectroscopy and gel permeation chromatography(GPC, M_n=2.2×10⁴, M_w/M_n=1.38). Subsequently, poly(HPMA)-APMA-DTPA was conjugated with ^99mTc radionuclide. Prolonged retention of poly(HPMA)-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography(SPECT-CT) at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-^99mTc was also synthesized and characterized for comparison. The data suggest that the poly(HPMA)-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.     

p16与原发性肝细胞癌的研究进展

p16基因又称肿瘤抑制基因(MTS1),是近年来发现的一个重要的抑癌基因,在细胞周期中发挥重要的调节作用.现对p16基因的结构、p16蛋白的作用途径以及该基因突变与原发性肝细胞癌的关系进行综述.     

胸膜穿刺针联合OB吻合胶构建615小鼠胃癌皮下移植瘤模型

目的 采用胸膜穿刺针联合OB吻合胶构建615 小鼠皮下移植瘤模型。方法 小鼠前胃癌细胞株(MFC)在无菌环境下培养制成浓度1×107个/mL细胞悬液,然后将悬液接种于小鼠右腋下,建成胃癌动物皮下移植瘤模型,利用瘤块进行体内传代3次,胸膜穿刺针法进行穿刺移植建立615小鼠皮下移植瘤模型。同时建立对照组(未放瘤块)用于对比,小鼠成瘤情况利用外观形态学和HE染色方法评价。结果 模型组小鼠体质量减轻。模型组肿瘤在第12天后生长较快,模型成功率为100%。外观形态学观察,模型组10只小鼠成瘤率100%,平均瘤重为(7.7160±0.2937)g;对照组成瘤率为0,模型组与对照组差异明显(P<0.01)。病理结果显示：模型组的瘤块体积较大,表面不规则,细胞核呈圆形、卵形或异形,核仁不显现,核分裂相较明显,是比较典型的胃癌组织的形态特征。结论 胸膜穿刺针联合OB吻合胶法构建615小鼠胃癌皮下移植瘤模型成功率高、并且具有高效、便利等特点,值得推广应用及研究。     

Diffusion-weighted MRI for the detection of colorectal polyps: feasibility study

The purpose of this study was to determine the feasibility of diffusion-weighted magnetic resonance imaging (DWI) for detecting colorectal polyps. DWI (high b-value of 1000 s/mm²) was prospectively performed in 26 symptomatic patients who were scheduled to undergo colonoscopy. DWI and colonoscopic findings were interpreted in a blinded manner. The sensitivity and positive predictive value (PPV) of DWI for the detection of clinically relevant polyps (≥ 6 mm) and colorectal cancer (CRC) were calculated on a per-lesion basis, using colonoscopy results as the standard of reference. Sensitivity, specificity, PPV and negative predictive value (NPV) on a per-patient basis were also calculated. Sensitivity and PPV on a per-lesion basis were 80.0% [95% confidence interval (CI): 49.0%–94.3%] and 72.7% (95% CI: 43.4%–90.3%) for polyps ≥ 6 mm and CRC. Sensitivity, specificity, PPV and NPV on a per-patient basis were 85.7% (95% CI: 48.7%–97.4%), 84.2% (95% CI: 62.4%–94.5%), 66.7% (95% CI: 35.4%–87.9%) and 94.1% (95% CI: 73.0%–99.0%) for polyps ≥ 6mm and CRC. In conclusion, DWI cannot yet be recommended in a clinical setting in which DWI is performed first and subsequent colonoscopy is only performed in patients with positive findings at DWI. Further (technical) developments are required to increase its diagnostic yield.     

鼻咽癌患者指甲的红外光谱研究

利用傅里叶红外光谱研究了20例正常人和3例鼻咽癌患者手指甲的红外光谱,结果表明：癌指甲样品与正常指甲样品的红外光谱在峰形、峰强度、峰频率等方面均存在明显差异;它们的最大区别是：酰氨Ⅱ带峰形的变化,δ_s(CH₃)峰的消失,以及874.0 cm-1附近有无吸收峰。还着重研究了磷酸二酯基团的对称和反对称伸缩振动;以及C—O基团伸缩振动峰的变化。并从蛋白质、核酸氢键的角度以及膜脂碳氢链排列及构像变化角度等方面分析了发生变化的原因。磷酸二酯基团的对称伸缩振动峰呈现有规律的变化, 即癌样品由1 080.0位移到1 077.6 cm-1, 反对称伸缩振动由1 239.4位移到1 238.4 cm-1, 表明指甲核酸分子内磷酸二酯键骨架的结构发生了改变。另外, 膜脂分子中的CH₂弯曲振动 δ(CH₂)的波数也有些改变, 即癌样品由1 453.1位移到1 453.7 cm-1。而且,峰的强度也有所增强, 说明癌患者指甲的膜脂中亚甲基链的无序状态较正常人的大。     

广西肝癌中HBV感染与N-ras基因突变的研究

应用ＰＣＲ－ＳＳＣＰ和免疫组化法检测２９例广西南部肝癌组织中的Ｎ－ｒａｓ基因突变和ＨＢＶ感染状况，结果，肝癌中Ｎ－ｒａｓ基因在第２￣３７密码子之间的突变率为７９．３％，其中２２例有２￣５个突变位点，该基因突变也见于癌旁组织，肝组织中ＨＢｓＡｇ和ＨＢｓＡｇ和ＨＢｘＡｇ检出率分别为８６．２％和７９．３％，两者具有相关性，并与Ｎ－ｒａｓ基因突变率呈相平行的趋势。因广西南部的肝癌与ＡＦＢ１污染有关，本研究     

Hypervascular hepatocellular carcinoma in the cirrhotic liver: diffusion-weighted imaging versus superparamagnetic iron oxide-enhanced MRI

Purpose

The purpose of the study was to validate diffusion-weighted imaging (DWI) in the assessment of hypervascular hepatocellular carcinoma (HCC) compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the cirrhotic liver.

Material and Methods

Forty-six consecutive patients with 106 hypervascular focal lesions in the cirrhotic liver who underwent DWI using three b factors and gadopentetate dimeglumine-enhanced dynamic MRI followed by SPIO-enhanced MRI were enrolled. Two independent radiologists evaluated two separated image sets (SPIO set, dynamic MRI and SPIO-enhanced T2*-weighted images; DWI set, DWI and dynamic MRI) and assigned confidence levels for diagnosis of HCC using a five-point scale for each lesion. Area under the receiver operating characteristic curve (A_z) was calculated for each image set.

Results

The A_z value of the DWI set was larger than the SPIO set by both readers (reader 1, 0.936 vs. 0.900, P=.050; reader 2, 0.938 vs. 0.905, P=.110). For the sensitivity (reader 1, 93.1% vs. 86.2%, P=.146; reader 2, 95.4% vs. 88.5%, P=.070) and specificity (reader 1, 89.5% vs. 73.7%, P=.250; reader 2, 79.0% vs. 73.7%, P=1.000) of HCC diagnosis, DWI sets were superior to SPIO sets without statistically significant differences.

Conclusion

For assessment of hypervascular HCC, DWI in combination with dynamic MRI provides comparable or slightly better information compared with the combination of dynamic and SPIO-enhanced MRI.     

Quantification of intermediates of the methionine and polyamine metabolism by liquid chromatography–tandem mass spectrometry in cultured tumor cells and liver biopsies

By means of liquid chromatography–tandem mass spectrometry we showed recently, that the chromosomal deletion or inactivation of the methylthioadenosine phosphorylase (MTAP) gene led to the accumulation of 5′-deoxy-5′-(methylthio)adenosine (MTA) in cancer cells. Here, we expanded the method to other key intermediates of the methionine and polyamine pathways to further elucidate the molecular consequences of a lack of MTAP activity. Employing multiple-reaction monitoring, limits of detection and lower limits of quantification in the range of 2.5–100 and 5.0–500 nM, respectively, were achieved according to the guidelines of the FDA, thus enabling the direct measurement of the metabolites in biological samples without prior enrichment and derivatization with an analytical repeatability of 1–3%. Relative standards deviations for quadruplicate 80% methanol extractions of metabolites from cultured tumor cells ranged from 1.1 to 25.5%, while the combined methodological and biological variability in metabolite concentrations in 10 liver biopsies was 11.8–51.4%. The method enabled the demonstration of changes in the concentration of intermediates of the methionine and polyamine metabolism other than MTA in hepatocellular carcinoma specimens lacking the enzyme MTAP compared to normal liver tissue.     

Metabonomic profiling of renal cell carcinoma: high-resolution proton nuclear magnetic resonance spectroscopy of human serum with multivariate data analysis

Metabonomic profiling using proton nuclear magnetic resonance (¹H NMR) spectroscopy and multivariate data analysis of human serum samples was used to characterize metabolic profiles in renal cell carcinoma (RCC). We found distinct, easily detectable differences between (a) RCC patients and healthy humans, (b) RCC patients with metastases and without metastases, and (c) RCC patients before and after nephrectomy. Compared to healthy human serum, RCC serum had higher levels of lipid (mainly very low-density lipoproteins), isoleucine, leucine, lactate, alanine, N-acetylglycoproteins, pyruvate, glycerol, and unsaturated lipid, together with lower levels of acetoacetate, glutamine, phosphatidylcholine/choline, trimethylamine-N-oxide, and glucose. This pattern was somewhat reversed after nephrectomy. Altered metabolite concentrations are most likely the result of the cells switching to glycolysis to maintain energy homeostasis following the loss of ATP caused by impaired TCA cycle in RCC. Serum NMR spectra combined with principal component analysis techniques offer an efficient, convenient way of depicting tumour biochemistry and stratifying tumours under different pathophysiological conditions. It may be able to assist early diagnosis and postoperative surveillance of human malignant diseases using single blood samples.     

Inhibitory potential of Hydroxychavicol on Ehrlich ascites carcinoma model and in silico interaction on cancer targets

Abstract

Hydroxychavicol (HC), a major phenolic derivative isolated from the leaves of Piper betle L. is well known for its antibacterial, antifungal and antimutagenic properties. The present study evaluated the in vivo antitumor activity of HC against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice and in silico interaction of HC with the receptors involved in the cancer. Hydroxychavicol (200 and 400?mg/kg bw) was orally administered for 21 consecutive days and was effective in inhibiting the tumor growth in ascitic mouse model. HC consistently reduced the tumor volume, viable cell count, lipid peroxidation and elevated the life span of HC treated mice. Besides the hematological profiles, SGOT and SGPT levels reverted back to normal and oxidative stress markers GSH, SOD and CAT also increased in HC treated groups. In silico docking analysis revealed that HC possessed potent antagonist activity against all the cancer targets demonstrating its inhibitory activity.