The anti-neoplastic effects of coumarin: an emerging concept

The recent article by Liu et al. provided for highly interesting reading. Interestingly, recent data suggests that coumarin may exert significant anti-neoplastic effects in a number of systemic malignancies. Coumarin is also of clinical benefit in mammary malignancies. For instance, it attenuates the extent of extremity lymphedema following breast cancer surgery and radiation therapy. In one recent study, an almost 12.5 % decline in the volume of upper extremity lymphedema was noticed. As a result, quality of life is significantly improved. Similar attenuation of tumor growth has been seen in pulmonary malignancies. It mediates these anti-neoplastic effects by attenuating Bcl-2 expression within the tumor cells. On the other hand, Bax expression within the tumor cells is markedly accentuated. These changes have recently been confirmed in A549 cells.     

分子靶向治疗在前列腺癌中的研究进展

前列腺癌是目前在全球男性中第二位最常见的肿瘤,其在恶性肿瘤死亡率中排名第六位[1]。在发病率方面,我国虽然不及西方国家,但是随着生活水平和诊疗技术的提高,也表现出了逐渐上升的态势。靶向治疗是以肿瘤细胞的特有位点作为治疗靶点,在纠正病变、稳定细胞、发挥更强的抗肿瘤活性的同时,能够对正常细胞减少毒副作用[2]。由于我们对于肿瘤发生发展的分子途径认知的逐渐提高,以及更好的利用这些途径作为有效的药物作用靶点,我们已经看到了越来越多的分子靶向药物的开发和生产随之增加。本文着重探讨了分子靶向药物对肿瘤的治疗起作用的不同的靶向机制,以及它们的研究现状及临床应用。     

17 beta-hydroxysteroid dehydrogenases and cancers

17β-Hydroxysteroid dehydrogenases (17HSDs) catalyze the interconversions between active 17β-hydroxysteroids and less-active 17-ketosteroids thereby affecting the availability of biologically active estrogens and androgens in a variety of tissues. The enzymes have different enzymatic properties and characteristic cell-specific expression patterns, suggesting differential physiological functions for the enzymes. Epidemiological and endocrine evidence indicate that estrogens play a key role in the etiology of breast cancer while androgens are involved in mechanisms controlling the growth of prostatic cells, both normal and malignant. Recently, we have developed, using LNCaP prostate cancer cell lines, a cell model to study the progression of prostate cancer. In the model LNCaP cells are transformed in culture condition to more aggressive cells, able to grow in suspension cultures. Our results suggest that substantial changes in androgen and estrogen metabolism occur in the cells during the process. These changes lead to increased production of active estrogens during transformation of the cells. Data from studies of breast cell lines and tissues suggest that the oxidative 17HSD type 2 may predominate in human non-malignant breast epithelial cells, while the reductive 17HSD type 1 activity prevails in malignant cells. Deprivation of an estrogen response by using specific 17HSD type 1 inhibitors is a tempting approach to treat estrogen-dependent breast cancer. Our recent studies demonstrate that in addition to sex hormone target tissues, estrogens may be important in the development of cancer in some other tissues previously not considered as estrogen target tissues such as colon. Our data show that the abundant expression of 17HSD type 2 present in normal colonic mucosa is significantly decreased during colon cancer development.     

Synthesis and preclinical evaluation of 68Ga-PSMA-BCH for prostate cancer imaging

Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. ⁶⁸Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with ⁶⁸GaCl₃ with >99% radiochemical purity and 59–74?GBq/μmol specific activity. In vitro and in vivo study of ⁶⁸Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with ⁶⁸Ga-PSMA-617, ⁶⁸Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating ⁶⁸Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.     

Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer

Green tea and its major constituent epigallocatechin gallate (EGCG) have been extensively studied as a potential treatment for a variety of diseases, including cancer. Epidemiological data have suggested that EGCG may provide protective effects against hormone related cancers, namely breast or prostate cancer. Extensive in vitro investigations using both hormone responsive and non-responsive cell lines have shown that EGCG induces apoptosis and alters the expression of cell cycle regulatory proteins that are critical for cell survival and apoptosis. This review will highlight the important in vitro mechanistic actions elicited by EGCG in various breast and prostate cancer cell lines. Additionally, the actions of green tea/EGCG in in vivo models for these cancers as well as in clinical trials will be discussed.     

前列腺PI-RADS V2.1评分联合血清PSA相关指标对灰区前列腺癌的诊断价值研究

摘要 目的：探讨前列腺影像报告和数据系统第2.1版（PI-RADS V2.1）评分联合血清前列腺特异抗原（PSA）相关指标对灰区前列腺癌的诊断价值。方法：回顾性分析2016年1月至2019年12月的187例经病理证实且PSA为灰区（4-10 ng/mL）的前列腺癌或前列腺增生患者资料。根据病理结果分为前列腺癌（PCa）组与前列腺增生组（BPH）组。由两名经验丰富的MRI诊断医师通过盲法对所有患者MRI图像进行PI-RADS V2.1评分,统计并计算血清PSA相关指标：总前列腺特异抗原（t-PSA）、游离前列腺特异抗原（f-PSA）、游离前列腺特异抗原与总前列腺特异抗原比值（f-PSA/t-PSA）、前列腺特异抗原密度（PSAD）。采用t检验比较各项指标在两组间的差异性,并使用受试者工作曲线（ROC）分析各项指标对灰区前列腺癌的诊断效能。结果：PI-RADS V2.1评分与PSAD在PCa与BPH组之间的差异具有统计学意义（P＜0.05）,而t-PSA、f-PSA、f-PSA/t-PSA在PCa与BPH组之间的差异均无统计学意义（P＞0.05）。根据ROC曲线分析,PI-RADS V2.1评分、PSAD、PI-RADS V2.1评分联合PSAD诊断灰区前列腺癌的曲线下面积（AUC）分别为0.814、0.671及0.838,且PI-RADS V2.1评分联合PSAD的AUC显著高于单独应用PI-RADS V2.1评分（Z=1.989,P＜0.05）与PSAD（Z=3.174,P＜0.05）。结论：PI-RADS V2.1评分与PSAD对诊断灰区前列腺癌具有较高诊断效能,且联合PI-RADS V2.1评分与PSAD能进一步提高诊断效能。     

不同临床病理特征的乳腺非特殊型浸润性癌分子亚型分析

目的:探讨不同临床病理特征的乳腺非特殊型浸润性癌的分子亚型分布特点。方法:回顾性分析309例乳腺非特殊型浸润性癌患者的临床资料,根据患者年龄、绝经情况、组织学分级和淋巴结转移情况分组,每组再根据免疫组化雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER-2)结果分为4种不同的分子亚型,分析各组中不同分子亚型的分布特点。结果:309例乳腺非特殊型浸润性癌中Lumina A型为137例(44.3%),Lumina B型为64例(20.7%),HER-2/neu型为63例(20.4%),basal cell-like型为45例(14.6%)。不同年龄段、绝经与否、不同组织学分级和淋巴结转移情况患者的分子亚型差异均具有统计学意义(P0.05)。结论:非特殊型浸润性癌的分子亚型以Luminal A型为主,其中异型性高,转移广泛的basal cell-like型的年龄分布呈现年轻化趋势。     

Molecular endocrinology and breast cancer--a reed before the wind lives on (a tribute to Professor Mike Reed)

Oestrogens in breast cancers are derived from both uptake from the circulation and in situ synthesis. Third generation aromatase inhibitors (AIs) effectively block aromatase activity within the breast. The effects of AIs on the molecular biology of breast cancers may be monitored in patients given neoadjuvant therapy. Changes in tumour gene expression associated with AIs is influenced by time of drug exposure and gene expression profiles may provide important information on tumour response/ resistance to AIs.     

Caspase-7在不同分子亚型乳腺癌中的表达及临床病理意义

目的:探讨含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase,Caspase-7,CASP7)在不同分子亚型乳腺癌中的表达及临床病理意义。方法:应用免疫组织化学方法检测CASP7在254例乳腺癌组织中的表达,重点观察该蛋白在不同分子亚型乳腺癌组织中表达的差异及与临床病理指标间的相关性,Kaplan-Meier法分析该蛋白表达与乳腺癌患者预后之间的关系。结果:Caspase-7在ER+PR+HER2+、ER+PR+HER2-、ER-PR-HER2+、ER-PR-HER2-中阳性表达率分别为37.2%、60.3%、17.0%、40.0%,在ER+/PR+/HER2-型中表达最高,在ER-/PR-/HER2+型中表达低,四组总体表达差异具有统计学意义(P0.001)。与ER、PR表达(均为r=0.194,P=0.002)呈显著正相关,与HER2表达2(r=-0.224,P0.001)呈显著负相关。在ER-PR-HER2+型乳腺癌中,CASP7的表达与肿瘤大小呈负相关(P=0.028),且与术后纵膈转移和脑转移呈正相关(均为r=0.307,P=0.026)。CASP7的表达与乳腺癌患者生存无显著相关性。结论:CASP7在不同分子亚型乳腺癌中表达存在差异,并且可能作为乳腺癌分子分型和预后预测的候选标记物。     

Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines

Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.     

3.0T MR波谱成像与扩散结合在前列腺中央腺体癌诊断中的价值

目的:探讨3.0T磁共振波谱成像(MRSI)结合扩散加权成像(DWI)在前列腺中央腺体癌中的诊断价值。方法:回顾性分析术前MRSI与DWI结合诊断为前列腺中央腺体癌的患者共18例,术后确诊为前列腺癌16例、前列增生1例、前列腺增生伴前列腺中度到重度炎症1例。其中3例已经确诊中央腺体癌为激素治疗后行MRI检查。比较患者癌区与对侧非癌区两组间的(胆碱+肌酸)/枸橼酸盐(CC/C)值。结果:无任何治疗的13例中央腺体癌区158个体素的CC/C值均值为2.684±1.7,非癌区196个体素的CC/C均值为0.49±0.08。(T值为2.778,P值均=0.0170.05),中央腺体癌区与对侧非癌区之间的CC/C值差异有统计学意义。3例激素去势治疗后癌区的CC/C均值为1.18±0.95,非癌区22个体素CC/C均值为0.46±0.255。(T值为1.196,P值均=0.3540.05)。激素治疗后中央腺体癌区与对侧非癌区之间的CC/C值差异无统计学意义。结论:MRSI结合DWI显著提高前列腺中央腺体癌的诊断。     

磁共振淋巴造影技术方法研究

目的：评估欧乃影介导的磁共振间质淋巴造影在诊断前列腺癌盆腔淋巴转移的可行性和安全性。方法：所有30例病理确诊前列腺癌患者,采用1.5T菲利浦超导型磁共振成像仪检查。先完成盆腔前列腺平扫,接着皮下注射造影剂欧乃影行三维增强磁共振淋巴造影术（3D CE-MRL）,最后欧乃影静脉注射盆腔前列腺增强扫描。结果：皮下注射后,欧乃影迅速吸收进入淋巴系统,引流区域各组淋巴结、淋巴管显示清晰。结论：皮下注射＂欧乃影＂行磁共振间质淋巴造影术诊断前列腺癌患者盆腔淋巴转移是可行和安全的。