Consensus primers targeting human papillomaviruses (HPVs) have biases in sensitivity toward certain HPV types. We applied 3 primer sets (GP51/61, MY09/11, PGMY09/11) in parallel on 120 Chinese cervical cancer specimens. GP51/61 exhibited a poor sensitivity for HPV52, for which the prevalence among squamous cell cervical cancer was underestimated from 14.6% to 0%. The fact that HPV52 should rank second in prevalence among squamous cell cervical carcinoma in Hong Kong could be missed if GP51/61, a worldwide commonly used primer set, was selected for HPV detection. Biases in HPV type-specific sensitivity may result in misprioritization of vaccine candidates. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; detection; genotype; vaccine; Chinese; Hong Kong; PCR Cervical cancer is the second most common cancer in women worldwide. Strong and consistent evidence accumulated over the past 2 decades confirms the aetiologic role of human papillomaviruses (HPVs) and provides a strong impetus for developing HPV vaccines to prevent cervical cancer. More than 100 HPV types have been identified, and at least 30 have been found in cervical cancers. 1 Given the diversity of HPV types and the largely typespecific immunity after natural infections, 2-4 it is important to delineate the prevalence of different HPV types found in cervical cancers so as to guide the selection of vaccine candidates. Most studies on HPV have employed consensus primers with an intention to cover a broad spectrum of HPV types. With the more than 10% sequence variation between HPV types, biases in sensitivity of a given primer set toward certain types could happen. In our study, we examined the influence of detection methods on assessing the prevalence of HPVs and thus their priority as cervical cancer vaccine candidates.
Material and methodsA total of 120 cervical cancer specimens (105 fresh frozen and 15 paraffin embedded; 89 squamous cell carcinoma, 26 adenocarcinoma, 4 adenosquamous carcinoma and 1 lymphoepitheliod carcinoma) collected from Hong Kong Chinese aged 26-84 years (mean 55 years; SD 13.9) were examined. Total DNA was extracted by the QIAamp DNA mini kit (QIAGEN, Hilden, Germany) and with the quality of extracted preparations confirmed by beta-globin PCR. 5 The clinical materials were collected with a written informed consent. Our study was approved by the local institutional ethics committee, and the human experimentation guidelines of the local institute were followed in the conduct of our study.HPV detection and typing was accomplished by 3 different methods in parallel. In the first method, HPV DNA was amplified by the GP51/61 primers that target an approx. 150 bp fragment of the L1 region. 5,6 The HPV type was identified by direct sequencing of PCR amplicons. In the second method, the MY09/ 11 primers that target an approx. 450 bp fragment of the L1 region was used for PCR. 7,8 HPV type was identified by restriction fragment length polymorphisms (RFLPs) using endonucleases RsaI and DdeI as previously described. 8 Ambiguous RFLPs w...
High frequency of persistent HPV infection, especially high-risk and multiple HPV infection, may explain why squamous intraepithelial lesions occurred frequently in patients with SLE. Patients with high inflammatory burden are at risk of acquiring HPV infection.
Objective To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen.Design Randomised controlled trial.Setting A tertiary teaching hospital.Population One hundred and thirteen women (66 premenopausal/ 47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy.Methods Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen.Main outcome measures De novo endometrial pathology at 1 year of tamoxifen.Results Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P = 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P = 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year.Conclusion LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.Keywords Breast cancer, endometrial polyps, levonorgestrel intrauterine system, tamoxifen.Please cite this paper as: Chan S, Tam W, Yeo W, Yu M, Ng D, Wong A, Kwan W, Yuen P. A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women. BJOG 2007;114:1510-1515
Human Kruppel-like factor 2 (KLF2) is a Cys 2 /His 2 zinc-finger-containing transcriptional factor, which is involved in multiple cellular pathways. Utilizing gene expression profiling to identify aberrantly expressed genes in ovarian cancer, we found that KLF2 was significantly and specifically downregulated in ovarian tumors. After reintroducing KLF2 into ovarian cancer cell lines, we observed decreased cell growth and increased sensitivity to DNA damage-induced apoptosis. Analysis of genes that could be potential targets of KLF2 revealed that KLF2 negatively regulated WEE1 expression. WEE1 encodes a tyrosine kinase that regulates the G2/M cell cycle transition. Expression of KLF2 markedly repressed the transcription of WEE1 by directly binding to an SP1/ CPBP motif located between À252 bp and the start codon of the WEE1 promoter. Both activation and zincfinger domains of KLF2 were required for this suppression of Wee1 expression. In addition, we demonstrated that Wee1 expression prevents cancer cells from undergoing apoptosis in response to DNA damage; however, this resistance was abolished by coexpression of KLF2, which inhibits WEE1 transcription. Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis.
HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study.
We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer.
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