Heat shock proteins in animal neoplasms and human tumours—a comparison

Heat shock proteins (HSPs) are implicated in all phases of cancer from proliferation, impaired apoptosis and sustained angiogenesis to invasion and metastasis. The presence of abnormal HSP levels in several human tumours suggests that these proteins could be used as diagnostic and/or prognostic markers, whilst the direct correlation between HSP expression and drug resistance in neoplastic tissues means they could also be used to predict cancer response to specific treatment. HSPs have also been successfully targeted in clinical trials modifying their expression or chaperone activity. Preliminary studies in veterinary medicine have also demonstrated the presence of altered HSP expression in neoplasms, and the study of carcinogenesis and the role of HSPs in animal models will surely be an additional source of information for clinical cancer research.     

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

Previously, safety and immunogenicity of human papillomavirus type 16 (HPV16) or 18 E7-pulsed dendritic cells (DC) vaccinations were demonstrated in a dose-escalation Phase I clinical trial which enrolled ten patients diagnosed with stage IB or IIA cervical cancer (nine HPV 16-positive, one HPV 18-positive). The goal of the study was to define the T-cell epitopes of HPV 16 or 18 E7 protein in these patients in order to develop new strategies for treating HPV-associated malignancies. This was accomplished through establishing T-cell lines by stimulating peripheral blood mononuclear cells with autologous mature DC pulsed with the HPV 16 or 18 E7 protein, examining the T-cell responses using ELISPOT assays, and isolating E7-specific T-cell clones based on IFN-γ secretion. Then, the epitope was characterized in terms of its core sequence and the restriction element. Twelve T-cell lines from eight subjects (seven HPV 16-positive, one HPV 18-positive) were evaluated. Positive T-cell responses were demonstrated in four subjects (all HPV 16-positive). All four were positive for the HPV 16 E7 46-70 (EPDRAHYNIVTFCCKCDSTLRLCVQ) region. T-cell clones specific for the E7 47–70 region were isolated from one of the subjects. Further analyses revealed a novel, naturally processed, CD4 T-cell epitope, E7 58–68 (CCKCDSTLRLC), restricted by the HLA-DR17 molecule. This work was supported by the National Institutes of Health (R21CA094507). An erratum to this article can be found at     

MSI-H colorectal cancers preferentially retain and expand intraepithelial lymphocytes rather than peripherally derived CD8<Superscript>+</Superscript> T cells

The healthy colorectal mucosa contains many resident intraepithelial lymphocytes (IELs) consisting of partially activated yet hyporesponsive CD8⁺ T cells. A predominant feature of colorectal cancers (CRCs) characterized by high levels of microsatellite instability (MSI-H) is heavy infiltration by an intraepithelial population of tumor infiltrating lymphocytes (iTILs). While it has been assumed that these iTILs originate from tumor infiltration by peripheral CD8⁺ effector T cells, their origin remains unknown. In light of the phenotypic and functional differences exhibited by IELs and peripheral T cells, elucidation of the precursor population of iTILs in MSI-H CRCs could clarify the role played by these lymphocytes in tumor progression. The aim of the present study was to investigate whether MSI-H CRCs interact differently with IEL- versus peripherally-derived CD8⁺ T cells. Using a Transwell assay system to mimic basolateral infiltration of tumor cells by lymphocytes, T cell migration, retention, proliferation and phenotypic alterations were investigated. Results indicate that MSI-H CRCs preferentially retain and expand IEL-derived cells to a greater degree than their microsatellite stable (MSS) counterparts. While MSI-H CRCs also retained more peripherally derived T cells, this number was considerably less than that from the IEL population. While interaction of IELs with either CRC type led to baseline lymphocyte activation, MSS CRCs induced upregulation of additional activation markers on retained IELs compared to MSI-H CRCs. These results suggest that the abundant iTILs present in MSI-H CRCs result from expansion of the preexisting mucosal IEL population and imply a limited prognostic role for iTILs in MSI-H CRC.     

宫颈上皮内病变与HPV相关

目的了解辽宁省妇女生殖道人乳头瘤病毒（Human Papillomavirus,HPV）感染情况,研究辽宁省妇女宫颈上皮内病变与HPV感染的相关性。方法回顾性分析600例行核酸分子快速导流杂交基因芯片技术（Hybri Max）检测的患者,该600例患者均行薄层液基细胞学技术（Liguid-based cytologic teset,LCT）检查,有127例患者行病理活检,结合3种方法研究HPV感染与宫颈病变的相关性。结果导流杂交HPV-DNA检测结果与LCT结果相结合,600例患者中,感染HPV的阳性率分别为正常32%（92/288）,Asc-us42%（87/208）,LSIL53%（40/75）,HSIL86%（19/22）,癌100%（7/7）。导流杂交HPV-DNA检测结果与病理活检结果相结合,感染HPV的阳性率分别为：正常或慢性炎症36.17%（17/47）,CINⅠ66.67%（36/54）,CINⅡ-Ⅲ84.21%（16/19）,癌100%（7/7）,HPV感染阳性率随宫颈病变程度加重而明显升高。细胞学与组织学病理诊断符合率分别为LSIL72%（54/75）,HSIL86.36%（19/22）,SCC100%（7/7）。不同年龄阶段妇女感染HPV的阳性率依次为20-29岁46.76%（65/139）,30-39岁43.41%（79/182）,40-9岁40.48%（71/174）,50-59岁38.16%（29/76）,60-69岁37.50%（6/16）,70岁76.92%（10/13）。600例患者HPV感染总阳性率为40.83%（245/600）,在HPV21种亚型中,有19种亚型均被检测出,感染率最高的是HPV16 35.51%（87/245）,其它常见型别依次为HPV58,HPV6,HPV53,HPV18,HPV31,HPV52和cp8304。此外还发现高危型HPV16的感染率：正常或慢性炎症35.29%（6/17）CINⅠ33.33%（12/36）,CINⅡ-Ⅲ56.25%（9/16）,癌85.71%（6/7）,其感染率阳性率在各种程度的宫颈病变中占很大比重,也随宫颈病变的严重程度而增高,进一步论证了HPV16的高危性。结论辽宁省妇女HPV感染的主要亚型是HPV16,HPV58及HPV6.无论是与细胞学检测结果相结合还是与病理活检结果相结合,HPV感染阳性率均随宫颈病变程度的加重而增高。提示宫颈病变的防治重点应放在预防及治疗HPV感染。     

Reliability of a new virtual reality test to measure cervicocephalic kinaesthesia

The aim of this study was to investigate the cervicocephalic kinaesthesia of healthy subjects for gender and age effects and its reliability in a new virtual reality test procedure. 57 healthy subjects (30 male, 27 females; 18-64 years) were immersed into a virtual 3D scene via a headmounted display, which generated specific head movements. The joint repositioning error was determined in a static and dynamic test at the times T0, T1 (T0 + 10 minutes) and T2 (T0 + 24 hours). The intrasession reliability (T0-T1) and the intersession reliability (T0-T2) were analysed. In both tests no gender- or age-specific effects were found. In the overall group the means of the static test were 6.2°-6.9° and of the dynamic test were 4.5°-4.9°. The intratest difference in the static test was -0.16° and the intertest difference was 0.47°. The intratest difference in the dynamic test was 0.42° and the intertest difference was 0.37°. The static and dynamic test was reproducible in healthy subjects, with minor deviations, irrespective of gender and age. The smaller interindividual differences in the dynamic test could be beneficial in the comparison of healthy individuals and individuals with cervical spine disorders.     

MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells

MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3′UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggest that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.     

Codman颈椎前路钢板系统在脊髓型颈椎病中的应用（附96例报道）

目的：探讨Codman颈椎前路钢板系统治疗脊髓型颈椎病的临床运用疗效。方法：采用Codman颈椎前路钢板系统对96例脊髓型颈椎病患者行前路减压,植骨融合,钢板内固定术。结果：术后经6-14月门诊复查或随诊,全部患者术后症状明显改善或消失,颈椎椎间高度维持良好,植骨全部融合,未出现钢板、螺钉、松动或断裂。结论：Codman颈椎前路钢板系统是一种操作较为方便、安全、有效,固定牢靠的颈椎内固定器械。     

Altered expression of cellular membrane molecules of HLA-DR, HLA-G and CD99 in cervical intraepithelial neoplasias and invasive squamous cell carcinoma

OBJECTIVE: The aim of this study was to investigate the role of HLA-DR, HLA-G and CD99 during cervical carcinogenesis and to examine the prognostic significance of these protein expressions in invasive squamous cell carcinoma (SCC). METHODS: Using specific antibodies for HLA-DR, HLA-G and CD99, we examined protein expressions in 19 normal cervix, 15 mild dysplasia (CIN I), 22 moderate dysplasia (CIN II), 23 severe dysplasia (CIN III), and 34 invasive squamous cell carcinoma by immunohistochemistry. And we detected the expression of Ki67 in the same specimens. RESULTS: None of normal cervix and CINs except three cases of CIN III expressed HLA-DR. HLA-DR expression increased progressively with the grade of the tumor, and significant differences could be observed between grade 1 and grade 2 (P<0.01) and between grade 1 and grade 3 (P<0.05). In all normal epithelial control samples, HLA-G expression was seen in ectocervical squamous and endocervical columnar epithelium and the staining was strong and uniform. Only a small proportion of CINs and SCCs showed reduced expression of HLA-G. Compared with the results in the control samples, CINs and SCCs showed significantly reduced expression of HLA-G (P<0.001). SCCs showed significantly increased expression of CD99 when compared with normal cervix and CINs (P<0.05). Ki67 was expressed in all specimens. Significant differences were observed between CINs and normal cervix (P<0.001) and SCCs and controls (P<0.001), but no significant differences could be observed between SCCs and CINs. None of the expressions of these proteins was associated with any of clinicopathological parameters. CONCLUSIONS: These results indicate that increased expression of HLA-DR and CD99 may be related to the evolution of cervical cancer. All protein expressions were not associated with clinicopathological parameters.     

未绝经宫颈癌患者肿瘤组织中环氧合酶2的表达及其临床意义

目的探讨环氧合酶2(COX-2)在宫颈癌组织中的表达与月经周期的关系及其临床意义。方法选取47例未绝经宫颈癌手术病人,病史结合子宫内膜HE染色观察判断患者所处月经周期时段,采用免疫组织化学SP法检测宫颈癌组织中COX-2及增殖细胞核抗原(PCNA)的表达,计算机图像分析COX-2免疫染色密度值及PCNA标记指数(LI)。结果宫颈癌组织中COX-2表达阳性者增生期表达强于分泌期(P<0.05),但阳性率无显著性差异(P>0.05),COX-2阳性癌组织中PCNALI高于阴性者,差异有显著性(P<0.01)。有淋巴结转移者COX-2的表达高于无转移者(P<0.05),宫颈癌组织中COX-2的表达与FIGO临床分期、组织分化程度无显著相关性(P>0.05)。结论未绝经宫颈癌患者肿瘤组织中COX-2的表达在增生期较分泌期明显增加,并参与调节肿瘤的生长、转移。     

A review of methods to assess coactivation in the spine

Coactivation is an important component for understanding the physiological cost of muscular and spinal loads and their associations with spinal pathology and potentially myofascial pain. However, due to the complex and dynamic nature of most activities of daily living, it can be difficult to capture a quantifiable measure of coactivation. Many methods exist to assess coactivation, but most are limited to two-muscle systems, isometric/complex analyses, or dynamic/uniplanar analyses. Hence, a void exists in that coactivation has not been documented or assessed as a multiple-muscle system under realistic complex dynamic loading. Overall, no coactivation index has been capable of assessing coactivation during complex dynamic exertions. The aim of this review is to provide an understanding of the factors that may influence coactivation, document the metrics used to assess coactivity, assess the feasibility of those metrics, and define the necessary variables for a coactivation index that can be used for a variety of tasks. It may also be clinically and practically relevant in the understanding of rehabilitation effectiveness, efficiency during task performance, human-task interactions, and possibly the etiology for a multitude of musculoskeletal conditions.