区域效应——一个前列腺癌早期诊断的新思路（英文）

目前临床上有许多怀疑前列腺癌但穿刺阴性的病例,为了避免漏诊,多数患者必须接受重复穿刺。尽管部分患者经重复穿刺确诊为前列腺癌,而更多患者经过长期随访以及反复穿刺最终确诊为良性病变。近期研究证实,癌灶附近的组织学表现正常的组织中也可发生与癌灶相似的分子改变。因此,我们认为在前列腺癌的发生过程中存在区域效应。在这一理论指导下,选择适当的可反映前列腺癌区域效应的标记物,在穿刺阴性的标本中检出与癌灶相似的分子改变,就可以帮助临床医生在常规病理诊断之前,提前预测前列腺癌的发生。如果能够找到这样的标记物,并在大规模的诊断试验中证实其可行性,那么就可以极大地改善前列腺癌诊断的现状。     

Annexin Ⅰ蛋白在人前列腺癌中的表达及临床意义

目的:探讨Annexin Ⅰ蛋白在前列腺癌组织中的表达及其与前列腺癌发生、发展、转移及预后的关系.方法:回顾性分析110例前列腺癌及40例前列腺增生组织中Annexin Ⅰ蛋白的表达与前列腺癌Gleason分级、年龄、临床分期、转移及预后的相关性.结果:前列腺癌患者的Armexin Ⅰ表达水平显著地低于良性前列腺增生症患者(P＜0.05);Annexin Ⅰ在低分化癌中表达较高,与高、中分化癌相比有显著性差异(P＜0.05);而高、中分化癌之间Annexin Ⅰ表达均较低,两者之间无显著性差异(P＞0.05).前列腺癌Annexin Ⅰ蛋白表达与年龄无关,而与临床分期、淋巴结转移及预后有关(P＜0.05).结论:Annexin Ⅰ蛋白表达下调与前列腺癌发生发展和预后密切相关,可作为反映前列腺癌生物学行为和判断预后的生物标记物.     

综述:脑衰老与阿尔茨海默病症状出现前阶段

脑衰老可分为生理性增龄变化与病理性变化,后者与阿尔茨海默病(Alzheimer's disease,AD)等神经退行性疾病的发生有关．生理性脑衰老与AD在发病早期具有相似的表现形式、病变特征、生化改变和发病机制．其共同的分子机制是异常蛋白质蓄积,提示两者有着相似的病理学基础,脑衰老可能是AD等神经退行性改变的最初级阶段,病理性脑衰老因素可能促进AD等神经退行性疾病的发生发展．临床前期AD(preclinical AD,PCAD)患者的脑、血液和脑脊液中可以检测到AD特定的生物标记物,但AD的临床症状并没有出现,因此也被称为“症状出现前AD(presymptomatic AD)”．PCAD和对照组比较,氧化应激指标和高度不溶性Aβ42并没有显著性升高,寻找早期PCAD发病过程中新的可用于临床早期诊断的生物标记物、药物靶点将成为我们的关注重点．     

AnnexinⅠ蛋白在人前列腺癌中的表达及临床意义

目的：探讨AnnexinⅠ蛋白在前列腺癌组织中的表达及其与前列腺癌发生、发展、转移及预后的关系。方法：回顾性分析110例前列腺癌及40例前列腺增生组织中AnnexinⅠ蛋白的表达与前列腺癌Gleason分级、年龄、临床分期、转移及预后的相关性。结果：前列腺癌患者的AnnexinⅠ表达水平显著地低于良性前列腺增生症患者（P〈0．05）;AnnexinⅠ在低分化癌中表达较高,与高、中分化癌相比有显著性差异（P〈0．05）;而高、中分化癌之间AnnexinⅠ表达均较低,两者之间无显著性差异（P〉0．05）。前列腺癌AnnexinⅠ蛋白表达与年龄无关,而与临床分期、淋巴结转移及预后有关（P〈0．05）。结论：AnnexinⅠ蛋白表达下调与前列腺癌发生发展和预后密切相关,可作为反映前列腺癌生物学行为和判断预后的生物标记物.     

肝脏局灶性结节的超声造影诊断

目的:分析探讨超声造影在肝脏局灶性结节中的应用价值,为以后的临床诊断提供可靠性参考。方法:回顾性分析2011.10-2013.9期间来我院门诊以及住院的40例经病理证实为肝脏局灶性结节患者的超声造影表现,通过二维灰阶超声检查,40名患者共发现50个结节。患者先后进行肝脏超声造影检查及超声引导下经皮肝穿刺活检术。总结病例之间的相关关系以及造影表现的特殊性与一般性。结果:超声造影对肝脏良恶性病灶的诊断能力很好,对结节的敏感性85.8%,特异性99%、阳性预测值95%,阴性预测值96%,准确率95%。结论:肝脏局灶性结节的超声造影诊断有助于临床上判定局灶性结节良恶性,可以为临床提供更好的诊断依据,但是,由于许多假阳性的原因,故对于某些缺乏特异性的超声造影表现,需要其他方法或是穿刺活检进行辅助检查。     

HPV阳性口咽癌患者预后与T细胞浸润和新抗原负荷相关性分析

口咽癌是头颈鳞癌中重要的癌种之一,与人类乳头瘤状病毒(humanpapillomavirus,HPV)感染有关,其发病率逐年上升。但在临床治疗过程发现,HPV阳性口咽癌患者整体预后好于HPV阴性患者。目前,导致这一现象发生的分子机制尚不明确。本研究利用TCGA数据库,对HPV阳性和阴性患者的免疫细胞浸润和效应功能以及新抗原负荷进行了生物信息学分析。结果发现,HPV阳性患者的总体生存率比HPV阴性患者显著提高。对肿瘤组织中的免疫细胞相对丰度进行分析显示,HPV阳性患者的CD8+T细胞较HPV阴性患者显著提高,其效应分子IFN-γ和Granzyme B表达量显著升高。同时对新抗原数目进行分析发现,HPV阳性患者肿瘤组织中新抗原较HPV阴性患者低。本研究结果为HPV相关口咽癌的治疗提供了一定的基础理论支撑。     

BRAF~(T1799A)突变、RET/PTC重排对术前诊断甲状腺乳头状癌的作用

目的:探讨术前超声引导下细针抽吸细胞学检查(US-FNAB)联合BRAFT1799A突变、RET/PTC1及RET/PTC3重排对诊断甲状腺乳头状癌(PTC)的特异性及敏感性,为临床术前准确诊断PTC选择适用的分子标记物。方法:收集346个超声怀疑为甲状腺恶性结节的US-FNAB细胞标本及对应结节(152个)的术后新鲜组织,采用PCR分别扩增BRAFT1799A、RET/PTC1及RET/PTC3基因,产物经基因测序证实。结果:346个甲状腺术前穿刺的结节中,选择观察而未手术的结节192个,手术治疗152个,未接受手术建议的结节2个。术前US-FNAB的细胞标本中共检测到51个结节发生BRAFT1799A突变,其细胞学分类为36个恶性,11个可疑恶性,4个良性。该51个结节术后病理证实均为PTC。20个发生RET/PTC1重排,其术前细胞学结果为17个恶性,2个可疑恶性,1个滤泡性肿瘤或可疑滤泡性肿瘤,术后病理证实均为PTC。3个结节发生RET/PTC3重排,其术前细胞学结果为恶性,术后病理证实均为PTC。对45个术前US-FNAB标本检测BRAFT1799A突变阴性而术后病理证实为PTC的结节,将其对应结节的术中组织行该基因的检测,仅有1个结节的术后组织中检测到该突变。本研究中,术前US-FNAB联合多分子标志物的检测,将细胞学诊断PTC的敏感度由73.96%提高到92.71%。结论:术前US-FNAB联合多分子标志物的检测可提高其诊断PTC的敏感性及特异性,并有助于患者的个体化诊治。     

血清PSA含量与前列腺癌临床分期、病理分级的相关性

目的:探讨血清前列腺特异性抗原(PSA)与前列腺癌(PCa)临床分期、病理分级的相关性.方法:对自2004年7月～2009年12月南京市13692例50岁以上的男性在健康体检时行血清PSA检测.以PSA≥4.0ng/ml定为前列腺癌可疑病例.建议行前列腺穿刺活检以确诊.共筛查出PCa患者140例,比较不同PSA值PCa患者的Gleason评分及临床分期.结果:随着PSA值的升高,前列腺癌筛查阳性率亦随之升高,低分化前列腺癌患者血清PSA含量明显高于高分化前列腺癌和中分化前列腺癌患者(P＜0.05),晚期前列腺癌患者血清PSA含量明显高于早期PCa患者(P＜0.01).血清PSA含量≥20ng/ml的前列腺癌人群中低分化前列腺癌及晚期前列腺癌的比例高于血清PSA含量＜20ng/ml的前列腺癌人群(P＜0.01).结论:血清PSA可以为前列腺癌患者的诊断、治疗及预后判断提供重要依据.     

乳腺浸润性癌患者血清标记物B7-H4分子含量变化的临床意义研究

目的:探讨新发现的血清标记物B7-H4在乳腺浸润性癌患者血清中的含量变化及其临床诊断价值.方法:通过RT-PCR技术检测确诊为乳腺浸润性癌的58例患者治疗前后及30例健康妇女的血清中B7-H4mRNA含量变化,用ELISA夹心法检测患者血清中的B7-H4分子的水平变化,采用CA125 Ⅱ试剂盒检测所有患者CA125水平的变化,分析比较检测过程中B7-H4分子与CA125分子的特异性与敏感度.结果:RT-PCR检测结果发现大部分乳腺浸润性癌患者血清中B7-H4基因的mRNA含量明显升高(P<0.05);治疗后其水平明显下降但一般仍高于正常水平(P<0.05),Western-blot检测也得到了类似的结果.在乳腺浸润性癌的检测过程中:B7-H4分子的特异度明显低于CA125分子,而其敏感度却明显高于CA125分子;二者联合使用时检测的特异度与敏感度均显著提高(P<0.05).结论:血清中B7-H4分子的含量升高可以作为一个癌变的高危指标.     

前列腺疾病的MRI诊断

本文总结和分析了37例前列腺良性肥大、结节性增生和13例前列腺癌的MRI表现。提出了前列腺良性肥大、前列腺癌和前列腺良性增生结节与前列腺癌结节的诊断和鉴别诊断要点。分析了前列腺癌MRI临床分期的价值。文章认为MRI的软组织分辨力高,成像参数多、成像平面多,在诊断前列腺疾病中有相当的地位。尤其在前列腺癌的分期中有重要的作用,可协助临床制订合适的治疗方案。但MRI在良恶性前列腺结节的鉴别中仍有不足,二者的形态和信号有部份重叠交叉,妨碍了MRI做出准确的判断。最后的确诊仍依赖穿刺活捡取得病理诊断。     

前列腺特异性抗原在前列腺癌诊断中的应用进展

已经证明,前列腺特异性抗原（PSA）是一种有价值的前列腺癌（PCa)肿瘤标记物,血清PSA的广泛使用提高了前列腺癌的检出率,使晚期癌患得明显减少。然而,PSA对PCa的检测缺乏特异性,由于其高的假阳性率,引起许多不必要的活检。为了提高PSA对PCa诊断的特异性,降低不必要的活检,众多学正在探讨与PSA相关的几项参数的临床应用价值,本就此作一综述。     

Prostate cancer: risk assessment and diagnostic approaches

The successful treatment of prostate cancer relies on detection of the disease at its earliest stages. Although prostate-specific antigen (PSA)-based screening has been a significant advance in the early diagnosis of prostate cancer, identifying specific genetic alterations in a given family or patient will allow more appropriate screening for early disease. Mapping and identification of specific prostate cancer susceptibility genes is slowly becoming a reality. Other prostate cancer risks include a family history, race, and possibly serum markers such as insulin-like growth factor-I (IGF-I). Once a high-risk man is identified, transrectal ultrasound (TRUS)-guided biopsies are the standard to diagnose prostate cancer. Although TRUS is an advance over traditional digitally directed biopsies, it represents a random sampling of the prostate since most lesions cannot be visualized. Newer modalities such as ultrasound contrast agents, pattern recognition, and artificial neural networks (ANNs), applied to TRUS images, may improve diagnostic accuracy. If a man at risk for prostate cancer has undergone a negative TRUS biopsy, the decision for the need for additional biopsies is problematic. Use of PSA derivatives such as free and total PSA and the initial biopsy abnormalities such as atypia or high-grade prostatic intraepithelial neoplasia may define those patients in need of follow-up biopsy.     

Molecular therapeutics in prostate cancer

The purpose of this review is to provide information on the molecular basis of prostate cancer biology and to identify some of the targets for therapy, and highlight some potential strategies for molecular treatment. Here we give a synopsis of what we have learned regarding molecular biology of cancer in general and the directions research might take in the future in order to impact prostate cancer specifically. This work is certainly not encyclopedic in nature and we apologize in advance to colleagues whose work we were no able to include. Hope lies in learning to utilize some of these molecular workings for better prevention, diagnosis, and treatment of the most common solid organ cancer in men. Prostate cancer is a formidable disease and at current rates of diagnosis will affect one-in-six men living in the United States (Greenlee et al., 2000) Many of these men are diagnosed at an early stage of the disease and can be effectively treated by surgery or radiation. However, a significant fraction of men are diagnosed with later stage disease or progress despite early curative therapeutic attempts. Unfortunately, many of these men succumb to prostate cancer, as management options are limited and not always successful. Through an understanding of the molecular processes that occur in the development and progression of prostate cancer, novel therapies will arise that will provide longer survival, better quality of life, and a chance for cure in men afflicted with this disease.     

Optimisation de l’utilisation du PSA

PSA is a tumor marker usually determined for prostate cancer at diagnosis for its pronostic value and at therapy follow-up. But lack of specificity of PSA for prostate cancer and variability between assays demonstrated by the quality program survey make this marker not valuable in mass screening program. Market control of Afssaps on analysis devices of PSA showed a correct harmonization for total PSA. Biological tools available and easy to perform could improve ability of PSA for early detection of prostate cancer at a curable stage without induction of unnecessary biopsies prescribed because elevated total PSA values.     

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare.     

Prostate cancer: epidemiology, screening, and biomarkers

Carcinoma of the prostate continues to be a major health problem in the United States. Beginning in 1988, a marked increase in detection of prostate cancer occurred due to the development of a test for prostate-specific antigen (PSA). Controversy exists, however, about the value of PSA as a tumor marker. Although it has prognostic significance both before and after definitive therapy for prostate cancer, it is unclear whether routine PSA screening will translate into a survival advantage for patients. Because of its limitations, PSA may not ultimately be a good enough marker to be used as a screening tool. However, molecular biology has led to a rapid rise in the number of potential new prostate tumor markers, which may eventually overcome the weaknesses of PSA. Considerable progress has occurred in the diagnosis and management of prostate cancer: more is understood about the risk factors for the disease, possible ways to prevent it, and new ways to diagnose and monitor it. These developments have already translated into better patient care, while also identifying where further improvements are needed.     

Earliest detection of oral cancer using non-invasive brush biopsy including DNA-image-cytometry: report on four cases.

OBJECTIVE: We describe four patients presenting early oral cancers, detected cytologically on non-invasive brush biopsies including DNA-image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. METHODS: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA-measurements were performed using a DNA-Image-Cytometer. CASE REPORTS: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA-cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). CONCLUSION: Non-invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA-image-cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA-aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practice.     

Le cancer de la prostate: Acquis et challenges pour l'an 2000

Principles of the diagnosis and treatment of prostate cancer at any stage are still improving. Early diagnosis is accessible throughout the use of the PSA test associated with digital rectal examination which lead to indicate transrectal biopsies. This allowed to treat patients at an earlier stage and significantly improved prognosis in the case of organ confined disease. Progress made in the radical prostatectomy technique have contributed to decrease the postoperative morbidity and is the treatment of reference in clinically localized disease. Radiation therapy still remains a valuable alternative, however, results are more difficult to evaluate. Hormonal treatment using androgen deprivation is indicated at the stage of metastasis. LHRH agonist associated with anti antiandrogens are as much efficacious as surgical castration. Unfortunately, the prognosis of advanced disease remains unpredictable. Objectives for the future will be to improve the diagnostic and staging of prostate cancer et to better define therapeutic indications; better understand the effects of androgen deprivation; and to propose new therapies for hormone refractory cancers.     

The significance of galectin-3 as a new basal cell marker in prostate cancer

Prostate cancer may originate from distinct cell types, resulting in the heterogeneity of this disease. Galectin-3 (Gal-3) and androgen receptor (AR) have been reported to play important roles in the progression of prostate cancer, and their heterogeneous expressions might be associated with different cancer subtypes. Our study found that in various prostate cancer cell lines Gal-3 expression was always opposite to AR expression and other luminal cell markers but consistent with basal cell markers including glutathione S-transferase-π and Bcl-2. This expression pattern was confirmed in human prostate cancer tissues. Our results also showed that prostate cancer cells positive with basal cell markers were more aggressive. Downregulation of Gal-3 expression resulted in increased apoptotic potential and decreased metastasis potential of prostate cancer cells. Our findings demonstrate for the first time that Gal-3 may serve as a new marker for basal characteristics of prostate cancer epithelium. This study helps us to better understand the heterogeneity of prostate cancer. The clinical significance of this study lies in the application of Gal-3 to distinguish prostate cancer subtypes and improve treatment efficacy with designed personalized therapy.     

Proteomic analysis of conditioned media from the PC3, LNCaP, and 22Rv1 prostate cancer cell lines: discovery and validation of candidate prostate cancer biomarkers

Early detection of prostate cancer is problematic due to the lack of a marker that has high diagnostic sensitivity and specificity. The prostate specific antigen (PSA) test, in combination with digital rectal examination, is the gold standard for prostate cancer diagnosis. However, this modality suffers from low specificity. Therefore, specific markers for clinically relevant prostate cancer are needed. Our objective was to proteomically characterize the conditioned media from three human prostate cancer cell lines of differing origin [PC3 (bone metastasis), LNCaP (lymph node metastasis), and 22Rv1 (localized to prostate)] to identify secreted proteins that could serve as novel prostate cancer biomarkers. Each cell line was cultured in triplicate, followed by a bottom-up analysis of the peptides by two-dimensional chromatography and tandem mass spectrometry. Approximately, 12% (329) of the proteins identified were classified as extracellular and 18% (504) as membrane-bound among which were known prostate cancer biomarkers such as PSA and KLK2. To select the most promising candidates for further investigation, tissue specificity, biological function, disease association based on literature searches, and comparison of protein overlap with the proteome of seminal plasma and serum were examined. On the basis of this, four novel candidates, follistatin, chemokine (C-X-C motif) ligand 16, pentraxin 3 and spondin 2, were validated in the serum of patients with and without prostate cancer. The proteins presented in this study represent a comprehensive sampling of the secreted and shed proteins expressed by prostate cancer cells, which may be useful as diagnostic, prognostic or predictive serological markers for prostate cancer.