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Background: We investigated the agreement and accuracy of preoperative magnetic resonance imaging (MRI) with postoperative pathological characteristics and stages of endometrial endometrioid carcinoma (EEC). Methods: We recruited 527 women with EEC who underwent staging surgery at a single medical institution. The preoperative MRI, stages, and clinical and pathological parameters, including myometrial invasion (MI), cervical invasion (CI), adnexal metastasis (AM), intra-abdominal metastasis, and pelvic and/or para-aortic nodal metastasis, were recorded and analyzed. The agreement and accuracy between the preoperative MRI findings and these parameters and stages were assessed. Results: The rate of the preoperative MRI-based clinical stage matching the postoperative surgical stage was 85.2% in International Federation of Gynecology and Obstetrics stage IA, 51.9% in stage IB, 35.5% in stage II, 5.3% in stage IIIA, 33.3% in stage IIIB, 28.6% in stage IIIC1, 64.3% in stage IIIC2, and 93.8% in stage IVB. The consistency between radiologists and pathologists was 80.5% for deep MI, 91.5% for cervical invasion, 92.2% for adnexal metastasis, 98.9% for intra-abdominal metastasis, and 87.5% and 92.2% for pelvic and para-aortic nodal metastases, respectively. The negative predictive value of intra-abdominal metastasis was the highest with 99.8%. Conclusions: Preoperative MRI could be an excellent tool for routine preoperative assessment to predict pathological parameters and stages of EEC, especially in excluding intra-abdominal metastatic disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish a national database of mutations in the fibrillin-1 ( FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population. In this study, we screened 294 patients from 157 families for the presence of FBN1 mutations using polymerase chain reaction/ denaturing high performance liquid chromatography (PCR/DHPLC). We identified 56 mutations in 62 of the 157 (40%) families including 49 single-base substitutions (36 missense mutations, seven nonsense mutations, and six splicing sites), one small insertion, four small deletions, one small indel (insertion and deletion), and one exonic deletion (Exon 36). When family history was taken into consideration, the mutation detection rate rose to 91% (29 of 32). We further investigated the phenotypic data and found that one third (47 of 157) of the families fit the Ghent criteria for MFS. Based on that data, the mutation rate was 98% (46/47). That finding implies that family history and the Ghent criteria play a more important role than clinical manifestations in establishing a clinical diagnosis of Marfan syndrome. Among the 56 mutations found in this study, 40 (71%) have not been registered in the Human Gene Mutation Database (HGMD) or in the Universal Mutation Database (UMD). This is the first study of the mutation spectrum of MFS in a cohort of patients in Taiwan. The database is expected to considerably improve genetic counseling for and medical care of MFS families. [ABSTRACT FROM AUTHOR]

Intraperitoneal tumors expressing high amounts of mesothelin such as malignant mesothelioma and ovarian cancers tend to develop ascites and result in significant morbidity and mortality in the patient. A suitable preclinical intraperitoneal model will assist in the illustration of the mechanisms of molecular oncogenesis and facilitate in addressing issues related to early screening, diagnosis, and therapy for intraperitoneal tumors.In the current study, an ascitogenic malignant tumor model (WF‐3) was created. The mobility and proliferation of WF‐3 and its precursor cells, WF‐0, were characterized using transwell and MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays. In addition, the in vivo tumorgenicity of WF‐3 and WF‐0 was determined using intraperitoneal injection of the tumor cells. Microarray analysis was performed using WF‐3 and WF‐0. Northern blot analysis was used to characterize the expression of the mesothelin gene in WF‐3 and WF‐0. Furthermore, the mesothelin levels in serum and ascites were used to correlate with tumor load of WF‐3 in tumor challenged mice.The WF‐3 tumor cells demonstrated relatively high proliferation and migration rates compared with the parental cell line, WF‐0. The tumors from the WF‐3 but not WF‐0 were capable of forming ascites and peritoneal‐based tumors after tumor challenge. The WF‐3 tumor model was also capable of implanting into multiple organs including the diaphragm, intestines, and peritoneal wall. Furthermore, the WF‐3 tumor expressed high levels of mesothelin, which is commonly observed in the majority of ovarian cancers, pancreatic cancer, and malignant mesothelioma. In addition, the authors found that the serum and ascites mesothelin levels correlated with tumor loads in tumor‐challenged mice.The data indicate that the WF‐3 murine tumor model may potentially serve as a good model for understanding the molecular oncogenesis of peritoneal tumors. In addition, the preclinical model may potentially be useful for the development of diagnostic and therapeutic methods against intraperitoneal cancers. Cancer 2007. © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. To investigate whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high-performance liquid chromatography. Methods. We investigated the MTHFR genotype of a cytosine-to-thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac catheterization and also for 195 healthy controls. Results. The overall genotype frequencies of the MTHFR C677T polymorphism were not significantly different between the CHD patients and the healthy control (P = 0.345). Furthermore, taking various subgroups of CHD patients into consideration, we noted a significantly increased proportion of homozygous TT genotypes for patients suffering from valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic arch, persistent truncus arteriosus, and aortopulmonary window, no statistically significant difference existed. Conclusions. The discrepancy in the distribution of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in the developmental mechanism of CHD. The increased percentage of homozygous TT genotypes might contribute to the pathogenesis of valvular PS and PA + IVS. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection, especially with the oncogenic genotypes, is the most important risk factor for developing cervical cancer. We focused on generating HPV16 E7-specific cytotoxic CD8+ T lymphocytes and evaluating HPV16 E7-specific immune responses in HPV16-infected and uninfected populations. Peripheral blood mononuclear cells (PBMCs) were first collected from an uninfected group with an human lymphocyte antigen (HLA) A2 haplotype (four volunteers). Mature monocyte-derived dendritic cells (DCs) were generated from the PBMCs and pulsed with one of two HLA-A2-restricted E7 peptides, aa 11–20[YMLDLQPETT] and aa 86–93[TLGIVCPI], as antigen presenting cells. The autologous naïve or cultured PBMCs were then cultured with peptide-pulsed DCs to detect the HPV16 E7-specific immune responses by a variety of techniques such as enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) assay and cytotoxic T lymphocyte assay. Interferon-γ (IFN-γ) from E7-specific cytotoxic CD8+ T lymphocytes stimulated with the respective peptide was detected by ELISA. Using ELISPOT analysis, a marked increase in the number of IFN-γ-secreting CD8+ E7-specific lymphocytes was observed following peptide stimulation. Cultured CD8+ T lymphocytes were highly cytotoxic against the CaSki cells. PBMCs were then colleted from an HPV16-infected population of the HLA-A2 haplotype, including four persons of HPV16 infection only, four with cervical intraepithelial neoplasia (CIN) lesions, and four cervical cancer patients. We then compared the immunologic responses to E7 between HPV16-infected and uninfected populations by ELISA and ELISPOT assay. The E7-specific immunologic responses of the HPV16-infected populations were significantly higher than those of the uninfected population. In addition, persons with an HPV16 infection only or those with CIN lesions generated higher E7-specific immunologic responses than cervical cancer patients. Our results demonstrate methods for evaluating E7-sepcific immunologic responses and reflect the biological responses of HPV16-infected people during different periods of cervical disease. [ABSTRACT FROM AUTHOR]

To evaluate whether the power Doppler vascularity index (PDVI) can predict the response to neoadjuvant chemotherapy (NACT) in cervical carcinoma. Twenty-five women with bulky early stage cervical carcinoma treated by NACT followed by surgery were enrolled. Their response to NACT was evaluated. Clinical characteristics and pathologic data were recorded. Transvaginal power Doppler was performed before, during and after NACT. PDVI was detected using power Doppler and a quantitative image processing system. Factors that can potentially correlate with the response to NACT were analyzed. Twelve (48%) patients showed a response (responders) to NACT and 13 (52%) were unchanged or had progressive disease (nonresponders) after NACT. Higher PDVI values were noted in tumors with lymphovascular emboli and pelvic lymph node metastasis both before and after NACT. The mean values of the PDVI of the nonresponders before (19.27 ± 6.01 vs. 12.28 ± 7.06, p = 0.014), during (20.2 ± 1.5 vs. 12.9 ± 2.1, p = 0.009) and after NACT (18.1 ± 6.0 vs. 9.3 ± 5.4, p = 0.001) were significantly higher than those of the responders. When the cutoff point for predicting nonresponders to NACT was set at a PDVI value of 15%, the sensitivity was 92.3% and the specificity 66.7%. The power Doppler vascularity index can predict the response to neoadjuvant chemotherapy in cervical cancer, and might be useful for the evaluation of response to chemotherapy in cancer patients in the future. [ABSTRACT FROM AUTHOR]

Beta-thalassemia is a common inherited disease, resulting from one or more of a total of more than 200 different mutations in the β-globin gene (HBB). Efficient and reliable mutation-screening methods are essential in order to establish appropriate prevention programs for at-risk populations based upon a molecular diagnosis. We have developed a rapid and highly-specific mutation screening test for the diagnosis of β-thalassemia by coupling heteroduplex and primer-extension analysis based on the denaturing high performance liquid chromatography (DHPLC) system. A total of 161 healthy heterozygous Taiwanese carriers featuring 10 different HBB mutations and 30 patients exhibiting 12 different compound heterozygous or homozygous HBB mutations were subjected to DHPLC. The elution profile for the heteroduplex analysis of DHPLC could be successfully used to identify the common disease-causing mutations of HBB. To further confirm the sequence variants, we developed a technique combining multiplex primer-extension analysis coupled with DHPLC for the genotyping of eight common disease-causing mutations in the HBB gene. Overall, by coupling heteroduplex and primer-extension analysis based upon DHPLC, we were able to unambiguously identify the most-common β-thalassemia mutations corresponding to more than 99% of HBB alleles among the Taiwanese population. In conclusion, compared to classic approaches to mutation screening for this malady, we suggest that DHPLC is an excellent technique to be applied to the genetic screening of prenatal and postnatal individuals as a part of a diagnosis program for β-thalassemia and provides a more-efficient, economic, and sensitive means to undertake such a screening program. Hum Mutat 22:326–336, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In recent studies, we have shown that baicalein and baicalin, 2 major flavonoids of Scutellaria baicalensis Georgi, exhibit anticancer activity against several cancers in vitro. In our present study, we assessed their potential as anti-angiogenic agents in vivo employing chicken chorioallantoic membrane (CAM) assay and in vitro human umbilical vein endothelial cells (HUVECs) culture. When CAMs were treated with either baicalein or baicalin for 48 hr, the angiogenic response induced by basic fibroblast growth factor (bFGF) was markedly reduced in a dose-dependent manner. Further characterization showed that both flavonoids exhibited dual antiproliferative (at low dose) and apoptogenic (at high dose) effects on HUVECs. In biochemical analysis, treatment of HUVECs with baicalein and baicalin for 24 hr resulted in a dose-dependent decrease in the matrix metalloproteinase (MMP)-2 activity. Moreover, the migration of endothelial cells and the differentiation of endothelial cells into branching networks of tubular structures in vitro were also inhibited by these 2 flavonoids in a dose-dependent manner. Baicalein is more potent than baicalin in anti-angiogenesis in vivo as well as in vitro. Taken together, the results of our study provide evidence that baicalein and baicalin possess an anti-angiogenesis potential that is a previously unrecognized biologic activity. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]