CD133在胃肠间质瘤的表达及其临床意义

目的 探讨胃肠间质瘤（gastrointestinal stromal tumor,GIST）中的CD133的表达及其与GIST临床病理特征的关系.方法 采用免疫组织化学法,检测122例胃肠间质瘤患者组织中的CD133、CD117、CD34、DOG-1、KI-67的表达情况.结果 CD133、CD117、CD34 、DOG-1、KI-67的阳性表达率分别为74.6%（91/122）、98.4%（120/122）、86.9%（106/122）、95.1%（116/122）、47.5%（58/122）.CD133的表达水平与胃肠间质瘤危险度分组高低、核分裂像数目、肿瘤部位有关（P〈0.05）,而与患者性别、年龄、肿瘤大小无明显相关性（P〉0.05）.CD133的表达水平与DOG-1的表达水平无明显相关性（P〉0.05）,而与CD117、CD34、KI-67的表达水平呈正相关.结论 CD133蛋白的表达可能与GIST的恶性行为与预后有关,与CD117、CD34和DOG-1联合检测对于判断GIST的病理性质可能具有重要价值.     

Plasma anti-Müllerian hormone as a biomarker for bovine granulosa-theca cell tumors: Comparison with immunoreactive inhibin and ovarian steroid concentrations

Granulosa-theca cell tumors (GTCTs) are the most frequently reported ovarian tumors in cattle. Clinically, GTCTs could be confused with other ovarian abnormalities; therefore, the only definitive diagnosis for such tumors is histopathology of a biopsy from the affected ovary. However, this is an invasive technique and unsuitable for farm conditions. As a result, the key aim of this study was to evaluate the diagnostic value of anti-Müllerian hormone (AMH), a glycoprotein hormone that is synthesized exclusively by ovarian granulosa cells, as a sensitive noninvasive biomarker for diagnosing GTCTs in cattle. To achieve this aim, we conducted two experiments. In experiment 1, four clinically healthy Japanese Black cows had blood samples taken daily over one estrous cycle to characterize their AMH profiles throughout the estrous cycle. Additionally, single blood samples were collected from 21 cyclic cows to clarify the physiological range of AMH. In experiment 2, cows with histologically confirmed GTCT (GTCT group, n = 9) and cows affected with cystic ovarian disease (COD group, n = 8) had one blood sample taken before extraction of the tumorous ovary or therapeutic treatment for the COD. Blood samples (n = 105) from cyclic cows (n = 25) in experiment 1 were assigned as a physiologically cyclic group (PC group). Plasma AMH, immunoreactive inhibin (ir-INH), estradiol-17β (E₂), testosterone (T), and progesterone (P₄) concentrations were assayed in all samples. In experiment 1, the mean plasma AMH concentration was 0.09 ± 0.003 ng/mL and did not show substantial fluctuation throughout the estrous cycle. In experiment 2, plasma AMH, ir-INH, and E₂ concentrations were significantly elevated in the GTCT group in comparison with the PC group; among these parameters, only the AMH concentrations were significantly higher in the GTCT group than in the COD group. The area under the receiver operating characteristic curve of AMH for diagnosis of GTCT was 0.99 and was significantly higher than that of ir-INH (P < 0.001) and E₂ (P < 0.01). Moreover, the AMH at a cutoff point of ≥0.36 ng/mL had the highest diagnostic accuracy (99.2%), sensitivity (100%), and specificity (99.1%) compared with the other tested parameters. In conclusion, plasma AMH concentration is probably a more reliable and sensitive biomarker for bovine GTCTs than the concentrations of ir-INH or ovarian steroids.     

Therapeutic angiogenesis for revascularization in peripheral artery disease

Therapeutic angiogenesis for peripheral artery disease (PAD), achieved by gene and cell therapy, has recently raised a great deal of hope for patients who cannot undergo standard revascularizing treatment. Although pre-clinical studies gave very promising data, still clinical trials of gene therapy have not provided satisfactory results. On the other hand, cell therapy approach, despite several limitations, demonstrated more beneficial effects but initial clinical studies must be constantly validated by larger randomized, multi-center, double-blinded, placebo-controlled trials. This review focuses on previous and recent gene and cell therapy studies for limb ischemia, including both experimental and clinical research, and summarizes some important papers published in this field. Moreover, it provides a short comment on combined gene and cell therapy approach on the example of heme oxygenase-1 overexpressing cells with therapeutic properties.     

Polymorphisms in the IL-18 and IL-12B genes and their association with the clinical outcome in Croatian patients with Type 1 diabetes

Genetic variants of IL-18 and IL-12B may be important in immunoregulatory abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM), that contribute to individual differences in response to a treatment. Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease.     

Novel PTEN germline mutation in a family with mild phenotype: Difficulties in genetic counseling

PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome and Proteus-like syndrome. PTEN mutations have been more recently reported in children with macrocephaly and autism spectrum disorders or mental retardation, without other symptoms of PHTS. Although tumor risk has not been evaluated in these patients and their relatives, the same surveillance as for Cowden syndrome is usually proposed. We report a family including patients carrying a novel PTEN mutation and presenting with a mild phenotype consisting of macrocephaly, hypotonia during the first year of life and mild learning disabilities, without autistic features. None of these patients exhibited PTHS-related symptoms such as tumors, lipomas, vascular malformations or pigmented macules of the glans penis. This report raises the question of extending the indications of PTEN mutation screening to familial macrocephaly with learning disabilities. Detection of a mutation in this family led to difficult questions about surveillance, genetic counseling and familial information since the mother declined tumor screening and disclosure of genetic risk information to at-risk relatives.     

Association study between of Tie2/Angiopoietin-2 and VEGF/KDR pathway gene polymorphisms and vascular malformations

Vascular malformations (VMs) are common congenital and neonatal dysmorphogenesis. VMs mostly occur sporadically with a few exceptions of inheritability. Tie2/angiopoietins-2 (Ang-2) and VEGF/KDR pathways are known to be involved in normal and pathogenic angiogenesis. Our study was aimed to test the contribution of these pathway gene variants to VMs. A total of 8 variants were found among 103 VM patients and 142 healthy controls. These variants comprised rs638203, rs639225, rs80338908 and rs80338909 in Tie2 gene, rs1870377 and rs2305949 in KDR gene, rs79337921 and rs34590960 in ANTXR1 gene. Our results indicated that rs638203 (p = 0.029) and rs639225 (p = 0.018) in Tie2 gene were associated with VM. A further bioinformatics analysis suggested the rs638203-G and rs639225-G might cause an abnormal splicing of Tie2 gene into to a defective protein. Our results identified two novel Tie2 gene polymorphisms with genetic susceptibility to VMs, although future functional validation of the two polymorphisms is warranted in the future.     

Relationship between leptin receptor and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, which is involved in the multi-system disease, and its etiology is still not clearly understood. It is currently considered that not only the genetic factors but also the environment factors play a crucial role in the pathogenesis of PCOS. Obesity plays an important role through the insulin, leptin and endocannabinoid system in the pathological process of PCOS, leading to more severe clinical manifestations. The aim of our present study is to investigate whether there is association between single nucleotide polymorphisms (SNPs) of Gln223Arg and Pro1019Pro in the leptin receptor gene (LEPR) and PCOS in a Korean population. Interestingly, a significant association was found between the Pro1019Pro in LEPR gene and PCOS, and a highly significant association was found between the Gln223Arg in LEPR gene and PCOS (P = 0.033, OR = 1.523, 95% confidence interval and P < 0.0001, OR = 0.446, 95% confidence interval). Moreover, genotype combination and haplotype analyses indicate that Gln223Arg and Pro1019Pro polymorphisms of LEPR are significantly associated with the risk of PCOS.     

Recent progresses in gene delivery-based bone tissue engineering

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.     

妇科恶性肿瘤术后阴道微生态状况分析

目的了解妇科恶性肿瘤术后患者阴道微生态的状况,探讨妇科恶性肿瘤术后阴道微生态评价的临床意义。方法选取100例妇科恶性肿瘤术后复查的患者,取阴道分泌物进行微生态评价,以同期30例绝经体检妇女作为对照。结果妇科恶性肿瘤术后阴道优势菌以乳酸杆菌为主的,占41%;菌群密集度多在＋ ＋ ～＋ ＋ ＋,占52%;菌群多样性多在＋ ＋ ～＋ ＋ ＋,44% ;PH^4.5,占35% ;VVC阳性率为4% ;阴道毛滴虫阳性率为7% ;BV阳性率为5% ;微生态失调的发生率占69%。结论（1）妇科恶性肿瘤术后,阴道微生态失调发生率明显增高;（2）妇科恶性肿瘤术后阴道微生态的失调与肿瘤的种类、恶性程度、手术范围、卵巢去留等无关,但术后时间越长,阴道微生态失调率越高;（3）评价妇科恶性肿瘤术后阴道微生态环境的状况,对预防与治疗术后生殖道感染具有重要指导意义。