Somatic Mutations of the PTEN/MMAC1 Gene in Fifteen Japanese Endometrial Cancers: Evidence for Inactivation of Both Alleles

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1 , a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors,'contributes to tumorigenesis in endometrial cancers.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

Three-Dimensional Evaluation of Innominate Bone Rotation in Female Patients with Developmental Dysplasia of the Hip

BackgroundPatients with developmental dysplasia of the hip (DDH) are known to have abnormal pelvic morphologies; however, rotation of innominate bone features remains unclear. Thus, we investigated innominate bone rotation in patients with DDH by measuring the associated angles and distances using three-dimensional (3D) computed tomography.MethodsWe defined four straight lines in pelvic 3D models: from the anterior superior iliac spine to the posterior superior iliac spine, from the anterior inferior iliac spine to the posterior inferior iliac spine, from the pubic tubercle to the ischial spine, and from the pubic tubercle to the ischial tuberosity. Similarly, we measured the angles formed by these lines using the vertical axis of the anterior pelvic plane on the horizontal plane and the horizontal axis on the sagittal plane. Additionally, we measured the distances between the femoral head centers and the acetabular centers in the coronal plane.ResultsThe difference in internal rotation angle between the superior and inferior parts of the iliac bone was significantly lower, by approximately 1.7°, in the DDH group than in the control group (p = 0.007); the difference between the inferior and superior parts of the ischiopubic bone was significantly higher, by approximately 1.5°, in the DDH group (p < 0.001). In the sagittal plane, the sum of the superior aspect of the iliac bone and the inferior aspect of the ischium was significantly lower in the DDH group (p = 0.001) than in the control group. The distances between the femoral heads and the acetabula were significantly greater in the DDH group than in the control group (p = 0.03, p < 0.01, respectively).ConclusionsPatients with DDH had a more internally rotated ilium and ischiopubic bone than normal individuals; however, it should be emphasized that internal rotation was reduced near the acetabulum, and the acetabulum was shifted laterally. Similarly, it was shown that patients with DDH had different rotations of the ilium and ischiopubic bone in the sagittal plane.     

Assessment of affinities of propranolol and bopindolol to membranes from COS-7 cell transiently transfected with beta-1- and beta-2-adrenoceptors using a radioligand-binding assay method

This study was performed to assess the affinities of propranolol, bopindolol, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA(2) values) obtained from the membrane-enriched fractions from the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea-pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to beta(1)-AR subtypes obtained from COS-7 cell membranes were 9.02 +/- 0.04, 7.44 +/- 0.12, 9.38 +/- 0.31, 6. 65 +/- 0.16, 5.55 +/- 0.14, 8.17 +/- 0.15 and 5.99 +/- 0.13, respectively. The rank order of pKi values for these agents to beta-(2)-ARs in COS-7 cell membranes was the same as that of beta(1)-ARs. In addition, good correlations were observed between pKi values of homogenates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In conclusion, these results suggested that binding characteristics of (3)H-CGP-12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues.     

Herbimycin A Suppresses the Reduction of Gap-junctional Intercellular Communication Induced by Tumor-promoting Phorbol Ester in 3T3-L1 Cells

We have examined the suppressive effect of herbimycin A on the reduction of gap-junctional Intercellular communication that is induced by a tumor-promoting phorbol ester in 3T3-L1 cells. Most cells in growth arrest participated in dye-coupling, as evaluated by the transfer between cells of a fluorescent dye (Lucifer Yellow CH). Treatment of cells with 0.25 μg/ml herbimycin A slightly enhanced the dye-coupling. This enhancement required treatment for periods as long as 24 h. Addition of 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid reduction of dye-coupling. However, addition of TPA did not suppress dye-coupling in cells pretreated for more than 24 h with herbimycin A. Pretreatment of cells for less than 6 h with herbimycin A did not suppress the TPA-induced reduction of dye-coupling. These results suggest that herbimycin A suppresses the reduction of gap-junctional intercellular communication that is induced by TPA through enhancement of the ability of the cells to participate in gap-junctional intercellular communication     

Blue rubber bleb nevus syndrome: Report of a patient with hemangiomas of the vaginal portion of the cervix appearing during pregnancy

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder showing venous malformations in the skin and gastrointestinal tract, and other internal organs. We encountered a patient with BRBNS in whom hemangiomas of the uterine cervix appeared during pregnancy. This was apparently the first reported occurrence. To avoid unexpected bleeding from hemangiomas, patients with BRBNS should be examined repeatedly for hemangiomas of the birth canal, and special care should be taken in deciding the mode of delivery.     

Effect of providing risk information on undergoing cervical cancer screening: a randomized controlled trial

Background

In Japan, the cervical cancer screening rate is extremely low. Towards improving the cervical cancer screening rate, encouraging eligible people to make an informed choice, which is a decision-making process that relies on beliefs informed by adequate information about the possible benefits and risks of screening, has attracted increased attention in the public health domain. However, there is concern that providing information on possible risks of screening might prevent deter from participating.

Methods

In total, 1,912 women aged 20–39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 3 groups. Group A received a printed reminder with information about the possible benefits of screening, group B received a printed reminder with information about possible benefits and risks, and group C received a printed reminder with simple information only (control group).

Results

Out of 1,912 participants, 169 (8.8%) participated in cervical cancer screening. In the intervention groups, 137 (10.9%) participated in cervical cancer screening, compared to only 32 (4.9%) of the control group (p < 0.001). In addition, logistic regression analysis revealed that there was no significant difference in screening rate between group A and group B (p = 0.372).

Conclusions

Providing information on the possible risks of screening may not prevent people from taking part in cervical cancer screening among a Japanese non-adherent population.     

Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.