Helical CT and MR imaging show similar accuracy in the evaluation of pelvic lymph nodes in patients with cervical carcinoma. Central necrosis is useful in the diagnosis of metastasis in pelvic lymph nodes in cervical cancer.
TXMicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3 0 -untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression-and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.Endometrial cancer is a common cause of gynecological cancer death. The most dominant subtype, endometrioid endometrial cancer (EEC), accounts for >80% of this cancer. Menopause and unopposed estrogenic stimulation are typical risk factors. Patients are generally treated with surgery, radiation, chemotherapy or hormone therapy. Patients with early stage disease have 5-year survival rates over 80%, however, about 15-20% develop metastasis. 1 These patients and those with advanced stage disease or recurrence have poor prognosis due to limitation of effective treatment. 2 Understanding the pathogenesis of this disease may provide insights for the development of novel therapeutic strategies.MicroRNAs (miRNAs) are small noncoding RNA molecules of 19-24 nucleotides that regulate gene expression posttranscriptionally through imperfect base pairing with the 3 0 -untranslated region (3 0 UTR) of target mRNAs, causing transcript degradation and translational inhibition. 3 Approximately 20-30% of all genes are targeted by miRNAs and a single miRNA may target as many as 200 genes. 4 In human cancers, >50% of the miRNA genes are located in chromosomal fragile sites, minimal regions containing loss of heterozygosity, minimal amplicons or common breakpoint regions. 5 DNA ...
Intravenous leiomyomatosis is a rare smooth muscle tumor. We report two cases of intravenous leiomyomatosis that grew along different routes of the venous system into the inferior vena cava and the right atrium. The different route of extension makes a difference in the ease of excision of tumor masses. Using MEDLINE together with the references in each publication, we identified all cases of intracardiac leiomyomatosis reported in the English literature in the period between 1980 and 2003 and performed a brief review on this potentially lethal disease entity.
MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.
The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.Cervical cancer is the third most common cancer in women worldwide. 1 Infection with human papillomavirus (HPV) is a necessary, though insufficient, cause of cervical cancer. [2][3][4][5] More than 40 different types of HPV have been detected from the female genital tract, and 15 of them (HPV16,18,31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82) are classified as high-risk based on the epidemiological association with development of cervical cancer. [6][7][8] Two prophylactic vaccines (Cervarix TM by GlaxoSmithKline, United Kingdom; and Gardasil TM by Merck Sharp and Dohme, NJ USA) are currently available for prevention of HPV infection and the subsequent development of cervical neoplasia. Worldwide, about 70-80% of invasive cervical cancers are caused by HPV16 and HPV18, which are covered by both vaccines. 9-12 However, the distribution of non-16/18 HPV types especially among cervical intraepithelial neoplasia varies markedly by geographic region. [13][14][15][16] A population-specific assessment on the prevalence, more importantly the attribution, of each HPV type is essential for policy makers to evaluate the population benefits and cost-effectiveness of the current and next generation vaccines. Such data is also necessary for formulating an HPV-based screening strategy, especially for deciding the spectrum of HPV types to be covered. Furthermore, data acquired before the widespread administration of HPV vaccine is a crucial baseline for monitoring the effectiveness of vaccination at the population level and for detecting HPV type replacement if it ever occurs.
Aim-To evaluate the eYciency of phenol/ chloroform, microwave, and Qiagen spin column based DNA extractions from paraYn wax embedded tissue for use in the polymerase chain reaction (PCR). In addition, to assess the reliability of amplifying a housekeeping gene to indicate successful viral DNA extraction. Methods-DNA samples extracted from 20 blocks of cervical carcinoma tissues using the three methods were subjected to PCRs targeting 509 bp and 355 bp of the globin gene, and 450 bp and 150 bp of human papillomavirus (HPV) DNA. Results-Microwave extraction showed the highest positive rate for globin PCR, whereas the spin column method was the most eYcient for HPV DNA extraction. When the 509 bp globin and 450 bp HPV PCR results were correlated, two of 10, eight of 12, and nine of 10 globin positive extractions prepared by means of the phenol/chloroform, microwave, and spin column methods, respectively, yielded HPV DNA of the expected size. For the globin negative samples, HPV was detected in three of 10, two of eight, and four of 10 samples. Conclusions-HPV DNA extraction was most eYcient using the Qiagen spin column and had the highest positive predictive value when a housekeeping gene was used as an indicator of successful viral DNA extraction; the phenol/ chloroform method was the least eYcient. The potential drawbacks of some extraction methods when using a human housekeeping gene to assess the quality of viral DNA extraction need to be considered. (J Clin Pathol 2001;54:401-403) Keywords: cervical cancer; DNA extraction; polymerase chain reaction ParaYn wax embedded tissues are a valuable source of DNA for analysis. The traditional method of purifying DNA from archival tissues using xylene dewaxing followed by phenol/ chloroform purification is labourious and requires multiple steps that are prone to cross contamination. Recently, alternative approaches have been used. [1][2][3] In most studies, the success of DNA extraction is assessed by amplifying a fragment of a housekeeping gene, and the number of positive samples are regarded as a denominator when calculating the prevalence of target pathogens. Whether such an assessment can guarantee the retention of an equivalent length of DNA of the target pathogen has not been fully elucidated. In our study, three methods were applied on a series of paraYn wax embedded tissues to compare their eYciency for purifying human and viral DNA, and to assess the reliability of using a housekeeping gene as an indicator for successful viral DNA extraction. Methods STUDY SAMPLESTwenty blocks of formalin fixed, paraYn wax embedded cervical squamous cell carcinoma stored for four to six years were analysed. For each case, four 5 µm thick slices were cut in triplicate. The area to be sectioned was examined carefully to ensure the inclusion of tumour tissue and that an equal amount of tissue was included in each set. Three diVerent DNA purification methods were performed for each case. Thorough cleansing was performed between cases and a new set of cutting instruments ...
The intracellular fatty acid-binding proteins (FABPs) are a well-conserved family that function as lipid chaperones. Ongoing studies are focused on identification of the mechanistic complexity and vast biological diversity of different isoforms of FABPs. However, the molecular mechanism of FABP5 in the regulation of milk fat synthesis in the mammary gland of dairy cows is still largely unknown. Here, we report that FABP5 acts as a critical regulator of terol response element-binding protein-1c (SREBP-1c) gene expression induced by methionine (Met) and estrogen (E2) in bovine mammary epithelial cells (BMECs). We observed that the expression of FABP5 was markedly higher in dairy cow mammary tissue during the lactating period than the puberty period and the dry period. FABP5 is located in the cytoplasm, and Met and E2 significantly increase the protein levels of FABP5 in BMECs. Using gene function study approaches, we revealed that FABP5 positively regulates SREBP-1c gene expression and promotes milk fat synthesis. We confirmed that FABP5 is required for Met- and E2-induced SREBP-1c gene expression and milk fat synthesis. We further uncovered that fatty acids are needed for FABP5-mediated SREBP-1c gene expression. Thus, our study demonstrates that FABP5 is a critical regulator of Met- and E2-induced SREBP-1c gene expression leading to milk fat synthesis.
Taurine, a β-aminosulfonic acid, exerts many cellular physiological functions. It is still unknown whether taurine can regulate milk synthesis in the mammary gland. Therefore, in this study we investigated the effects and mechanism of taurine on milk synthesis in mammary epithelial cells (MECs). Bovine MECs (BMECs) cultured in FBS-free OPTI-MEMImedium were treated with taurine (0, 0.08, 0.16, 0.24, 0.32, and 0.4 mM). Taurine treatment led to increased milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c protein expression, in a dose-dependent manner, with an apparent maximum at 0.24 mM. Gene function study approaches revealed that the GPR87-PI3K-SETD1A signaling was required for taurine to increase the mTOR and SREBP-1c mRNA levels. Taurine stimulated GPR87 expression and cell membrane localization in a dose dependent manner, suggesting a sensing mechanism of GPR87 to extracellular taurine. Collectively, these data demonstrate that taurine promotes milk synthesis via the GPR87-PI3K-SETD1A signaling.
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