子宫颈癌HPV16/18感染与微血管密度和血管内皮生长因子表达的关系

目的 探讨人乳头状瘤病毒16／18（HPV16／18）在子宫颈癌组织中的感染情况及与微血管密度（MVD）和血管内皮生长因子（VEGF）表达的关系。方法 用原位杂交法检测HPV16／18在60例子宫颈癌（鳞癌40例、腺癌20例）、29例宫颈上皮内肿瘤（CIN）和16例正常子宫颈组织中的HPV16／18感染情况；采用免疫组织化学方法（SP）检测VEGF蛋白的表达，并以CD34抗原作为血管内皮细胞标记，测定其微血管密度。结果 HPV16／18在子宫颈鳞癌、腺癌、CIN和正常子宫颈组织中感染率分别为67．50％（27／40）、35．00％（7／20）、68．97％（20／29）、6．25％（1／16）。HPV16／18感染率鳞癌组与腺癌组和正常组比较差异均有显著性意义（均P〈0．01），而鳞癌组与CIN组相比差异无显著性意义（P〉0．05）。随着宫颈病变的进展，MVD逐渐增大，VEGF的阳性表达率渐增高。MVD在以上5种组织间相比差异均有极显著性意义（均P〈0．01）。VEGF在子宫颈鳞癌、腺癌、CIN、正常宫颈组织细胞质中的阳性表达率分别为95．00％（38／40）、100．00％（20／20）、82．80％（24／29）、18．80％（3／16）。病变患者与正常者相比差异有极显著性意义（P〈0．01）。HPV16／18感染与VEGF表达呈正相关（r=0．245，P〈0．05），而与MVD无相关性（r=．04，P〉0．05）；VEGF的表达与MVD无相关性（r=0．01，P〉0．05）。淋巴转移阳性者MVD的表达量较阴性者高（P〈0．05）。结论 在子宫颈癌的发生发展中HPV16／18的感染起一定的作用，MVD与VEGF在子宫颈组织的不同病变中的表达均有差异性，推测VEGF有促进子宫颈癌组织血管形成作用，MVD与子宫颈癌的恶性程度密切相关。HPV16／18感染可能通过促进VEGF的表达而有利于子宫颈癌组织的生长。     

HPV与宫颈癌的研究进展

宫颈癌（cancer of cervix，CaCx）是国内外危及女性生命的高发肿瘤之一，仅次于乳腺癌，人乳头瘤病毒（human papillomavirus，HPV）的感染是宫颈癌发生发展的重要因素，就HPV与多个癌基因、抑癌基因的相互作用和HPV与其他病原微生物的协同作用方面探讨宫颈癌的发病机制以及对HPV的检测方法等研究进行综述。     

Preclinical refinements of a broadly protective VLP-based HPV vaccine targeting the minor capsid protein,L2

An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and long-lasting immune responses against all high-risk HPV types, would be effective after a single dose, and would be formulated in such a manner to allow for long-term storage without the necessity for refrigeration. We have developed candidate HPV vaccines consisting of bacteriophage virus-like particles (VLPs) that display a broadly neutralizing epitope derived from the HPV16 minor capsid protein, L2. Immunization with 16L2 VLPs elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types. In this study we introduce two refinements for our candidate vaccines, with an eye towards enhancing efficacy and clinical applicability in the developing world. First, we assessed the role of antigen dose and boosting on immunogenicity. Mice immunized with 16L2-MS2 VLPs at doses ranging from 2 to 25 μg with or without alum were highly immunogenic at all doses; alum appeared to have an adjuvant effect at the lowest dose. Although boosting enhanced antibody titers, even a single immunization could elicit strong and long-lasting antibody responses. We also developed a method to enhance vaccine stability. Using a spray dry apparatus and a combination of sugars & an amino acid as protein stabilizers, we generated dry powder vaccine formulations of our L2 VLPs. Spray drying of our L2 VLPs did not affect the integrity or immunogenicity of VLPs upon reconstitution. Spray dried VLPs were stable at room temperature and at 37 °C for over one month and the VLPs were highly immunogenic. Taken together, these enhancements are designed to facilitate implementation of a next-generation VLP-based HPV vaccine which addresses U.S. and global disparities in vaccine affordability and access in rural/remote populations.     

A Point Mutation at F1737 of the Human Nav1.7 Sodium Channel Decreases Inhibition by Local Anesthetics

Abstract: Voltage-gated sodium channels (VGSC) contribute to the initiation and propagation of action potentials within the nervous system. These channels are important targets for inhibition by several classes of drugs, including antiarrhythmics and local anesthetics. Structural and pharmacological studies have localized the binding of these drugs to a common site near the channel's intracellular pore region. Point mutations within this region disrupt local anesthetic inhibition of cardiac, CNS, and skeletal muscle VGSC subtypes. This study was designed to test whether a similar structural requirement for drug binding exists on the peripheral neuronal VGSC subtype; Na_v1.7. In support of this hypothesis, an alanine substitution for phenylalanine at position 1737 (F1737A) in the pore lining S6 segment of domain IV in human Na_v1.7 reduced both use- and state- dependent inhibition of the local anesthetics, lidocaine and tetracaine, by 8–21-fold. We also saw a 2–3-fold reduction in tonic inhibition with the F1737A mutant. The voltage dependence of both activation and inactivation were unaffected by the F1737A mutation, however, fast inactivation kinetics were impaired, such that a significant portion of inward current remained at the end of a 20-ms depolarization. These data suggest that F1737 forms a part of the high affinity binding of local anesthetics as well as mediating inactivation processes of neuronal Na_v1.7 channels.     

Testing for high‐risk HPV in cervical and tonsillar paraffin‐embedded tissue using a cartridge‐based assay

This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin‐fixed paraffin‐embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.     

唐山市某医院医护人员对HPV及其疫苗认知和接受度调查

目的:调查河北省唐山某医院医护人员对HPV及其疫苗的认知、态度和接受性,探究全科医师和护士对HPV疫苗接种的看法,为HPV疫苗的推广提供一定的基础。方法:采用自行设计的调查问卷,以自填式匿名方式调查唐山市某医院200名医护人员对HPV病毒及其疫苗的认知态度。结果:198名医护人员中,91.5%的医师和75.0%的护士曾经听说过HPV,53.2%的医师和47.7%的护士曾经听说过HPV疫苗,超过半数的医师和护士担心HPV疫苗的安全性(61.2%vs 65.8%)和有效性(59.6%vs 65.1),仅有23.4%医师和34.8%护士愿意接受该疫苗,53.1%医师和30.9%护士建议患者使用HPV疫苗,仅有30.0%左右医师和护士赞同让自己的子女接受HPV疫苗,65.3%医师和55.7%的护士建议满18周岁接种HPV疫苗。结论:医师和护士关于HPV病毒的认知水平较高,但不够全面,对HPV疫苗认知不足,多数医师和护士对HPV疫苗持观望态度。     

Tumour‐associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype,other tumour‐infiltrating inflammatory cell subsets and outcome

The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event‐free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.     

Human papillomavirus (HPV) infection and genotype frequency in the oral mucosa of newborns in Milan,Italy

Human papillomavirus (HPV) causes cutaneous and mucosal infections in both adults and children. In order to evaluate HPV prevalence and the spectrum of genotypes in the oral cavity of paediatric subjects, a retrospective study was carried out on oral-pharyngeal swabs collected from 177 newborns aged 0–6 months. HPV-DNA was detected by a nested-PCR; the viral typing was made through DNA sequencing. HPV infection was identified in 25 subjects (14.1%) and the sequence analysis showed eight distinct genotypes. These data confirm HPV detection in newborn oral mucosa. Further investigations are needed to clarify the methods of HPV acquisition.