Genetics of Endometrial Cancers

Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas

Establishment of Fetal Cranial and Intracranial Structure Volume Measurements using Three-dimensional Ultrasound Imaging in a Japanese Population

The goal of this study was to establish a normogram of the intracranial structure volumes in appropriate-for-gestational age (AGA) Japanese fetuses. This was a cross-sectional and prospective study of 211 AGA fetuses. The total intracranial, cerebrum, ventricle, choroid plexus, cerebellum, cerebellar vermis, and cavum septum pellucidum volumes were measured using three-dimensional (3D) ultrasound. The fetal cranial and intracranial structure volumes significantly increased with gestational age (GA). When using the GA as an independent variable and the fetal cranial or intracranial structure volumes as the dependent variable, the best-fit equation for the fetal brain was a second-order polynomial regression equation. We herein provide the first report of fetal cranial and intracranial structure volumes and their normal growth curves in normal Japanese fetuses. Future 3D ultrasound studies of volume and other intracranial fetal structures could provide valuable information about how such changes may correlate with long-term neurodevelopment and the results may be used for comparisons with fetal growth restriction in the future

Development of a High-intensity Focused Ultrasound Exposure Device for Reducing Skin Burn Risk

High-intensity focused ultrasound（HIFU）can non-invasively irradiate inside the body. However, when used to treat fetuses, it can cause thermal burns of the mother’s abdominal wall at the skin interface. This study was carried out to determine whether a modified HIFU transducer enabling split-aperture irradiation can prevent thermal burns. Two HIFU transducers were compared: a conventional transducer using full-aperture irradiation and a modified transducer using split-aperture irradiation. The modified transducer was divided into six sectors for split-aperture irradiation and had a larger surface area and a smaller F number（focal length/aperture diameter）than the conventional transducer. HIFU was delivered to eight sites on the left and right leg of a three-month-old baby pig under general anesthesia, and the sites were assessed for thermal burning by two or more dermatologists. The same person performed all irradiations. Full-aperture irradiation with the conventional transducer caused deep dermal burns at all target sites, while split-aperture irradiation with the modified transducer caused only epidermal burns or superficial dermal burns. Split-aperture irradiation using a modified HIFU transducer with six sectors and a smaller F number reduces the severity of skin burns, and thus will improve the safety of HIFU therapy

Clinical potential for noninvasive prenatal diagnosis through detection of fetal cells in maternal blood

Summary Fetal cells circulate in maternal blood and are considered a suitable means by which to detect fetal genetic and chromosomal abnormalities. This approach has the advantage of being noninvasive. Since the early 1990s, nucleated erythrocytes (NRBCs) have been considered good target cells for a number of techniques, including fluorescence-activated cell sorting and magnetic cell sorting, using antibodies such as anti-transferrin receptor and anti-?-hemoglobin antibodies, followed by analysis with fluorescence in situ hybridization or polymerase chain reaction. In the late 1990s, the National Institute of Child Health and Human Development Fetal Cell Isolation Study assessed the reliability of noninvasive prenatal diagnosis of fetal aneuploidy using NRBCs isolated from maternal circulation. This study revealed the limitations of NRBC separation using antibodies specific for NRBC antigens. A more recent study has demonstrated the efficiency and success of recovery of NRBCs using a galactose-specific lectin, based on the observation that erythroid precursor cells have a large quantity of galactose molecules on their cell surface. Thus, recent advances in this field enhance the feasibility of this diagnostic method. This review article focuses on various methods of detection of fetal cells within the maternal circulation, as well as the status of previous and current studies and the prospective view for noninvasive prenatal diagnosis using fetal cells from the maternal circulation

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing

Background: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. Results: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. Conclusions: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women

Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

BackgroundHuman papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences.MethodsThe entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins.ResultsAmong 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates.ConclusionsAmong the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome

Si–H Bond Activation of a Primary Silane with a Pt(0) Complex: Synthesis and Structures of Mononuclear (Hydrido)(dihydrosilyl) Platinum(II) Complexes

A hydrido platinum(II) complex with a dihydrosilyl ligand, [cis-PtH(SiH2Trip)(PPh3)2] (2) was prepared by oxidative addition of an overcrowded primary silane, TripSiH3 (1, Trip = 9-triptycyl) with [Pt(η2-C2H4)(PPh3)2] in toluene. The ligand-exchange reactions of complex 2 with free phosphine ligands resulted in the formation of a series of (hydrido)(dihydrosilyl) complexes (3–5). Thus, the replacement of two PPh3 ligands in 2 with a bidentate bis(phosphine) ligand such as DPPF [1,2-bis(diphenylphosphino)ferrocene] or DCPE [1,2-bis(dicyclohexylphosphino)ethane] gave the corresponding complexes [PtH(SiH2Trip)(L-L)] (3: L-L = dppf, 4: L-L = dcpe). In contrast, the ligand-exchange reaction of 2 with an excess amount of PMe3 in toluene quantitatively produced [PtH(SiH2Trip)(PMe3)(PPh3)] (5), where the PMe3 ligand is adopting trans to the hydrido ligand. The structures of complexes 2–5 were fully determined on the basis of their NMR and IR spectra, and elemental analyses. Moreover, the low-temperature X-ray crystallography of 2, 3, and 5 revealed that the platinum center has a distorted square planar environment, which is probably due to the steric requirement of the cis-coordinated phosphine ligands and the bulky 9-triptycyl group on the silicon atom

Umbilical cord insertion site in early gestation and development of placenta

Aim: To study the relation of umbilical cord insertion (CI) site in early gestation and placental development from the chorion villosum. Methods: We ultrasonically measured the distance between the internal cervical Os and the CI site (CID), the distance between the internal cervical Os and lower placenta edge (PLD), and placental thickness at early (10–12 weeks) and mid-gestation (18–20 weeks). Results: CID in early gestation (CID-Early) correlated with CID in mid-gestation (r2=0.171; P<0.01). CID-Early correlated with PLD in mid-gestation (r2=0.093; P<0.01). Thickness of chorion villosum or placenta in early gestation did not correlate with that at mid-gestation. Increasing thickness of placenta was significantly higher in long CID-Early (≥20 mm) cases than short cases (<20 mm) (P<0.05). Conclusions: The process of placental development and the placental location are affected by CI location at early gestation, and suggests that this process might be affected by poor blood supply from the low uterine segment when CI site is close to the internal cervical Os.Peer Reviewe

Successful Pregnancy in a Case of Behçet’s Disease after Treatment with Prednisolone

A 34-year-old woman (gravida 1, para 0) visited the Division of Reproductive Medicine/National Center for Child Health and Development due to infertility; she had also been suffering from incompletely treated genital ulcers and stomatitis for 10 years. This case was diagnosed as an incomplete-type Behçet’s disease (BD) at the Department of Maternal-Fetal Biology/National Center for Child Health and Development. Since no apparent abnormality was found in the general infertility test, artificial insemination with the husband’s semen (AIH) was performed for the patient with unexplained infertility, which failed. However, after treating BD with prednisolone, chronic inflammation (stomatitis and genital ulcer) and immunological abnormalities (Th2 and NK cell activity) improved, and conception was possible by AIH. Thus, prednisolone administration may have induced immune tolerance in the patient with BD, which may have contributed to the success of AIH