The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

Phenolic glycosides from berries of Pimenta dioica

Four new phenolic glycosides, (2-hydroxy-3-methoxy-5-allyl)phenyl beta- d-(6-O-E-sinapoyl)glucopyranoside (1), (1' R,5' R)-5-(5-carboxymethyl-2-oxocyclopentyl)-3 Z-pentenyl beta-D-(6-O-galloyl)glucopyranoside (2), (S)-alpha-terpinyl [alpha-L-(2-O-galloyl)arabinofuranosyl]-(1-->6)-beta-D-glucopyranoside (3), and (R)-alpha-terpinyl [alpha-L-(2-O-galloyl)arabinofuranosyl]-(1-->6)-beta-D-glucopyranoside (4), were isolated from the berries of Pimenta dioica together with eight known flavonoids. The structures of 1-4 were elucidated on the basis of MS and NMR data and enzymatic hydrolysis. All four glycosides showed radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals.     

Laparoscopy-assisted proximal gastrectomy with gastric tube reconstruction for early gastric cancer

Background  

In this report, laparoscopy-assisted proximal gastrectomy (LAPG) and gastric tube reconstruction using a mini-loop retractor (MLR) is described for the treatment of early gastric cancer.     

A case of paracecal hernia

A 63-year-old male patient suddenly suffered right lower abdominal pain. The patient had tenderness and rebound tenderness at the right lower abdomen. Marked small bowel dilatation and an intestinal obstruction were evident upon abdominal X-ray and abdominal computed tomography (CT) imaging. CT imaging also revealed a dilated small bowel cluster in a wrapped round shape in the right lower abdomen. The cecum and the ascending colon were displaced inward. Strangulation in the ileocecal region was suspected, and emergency surgery was performed. A part of the small bowel was incarcerated within the retrocecal recess, and the intestinal tract was strangulated in the hernia orifice, by which paracecal hernia was diagnosed. The strangulated intestinal tract was repositioned, and the orifice to the hernia was closed. Paracecal hernia is a rare disease; an internal hernia should always be considered in patients with ileus without a history of surgery.     

A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat

Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not only adults but also neonates. However, the side effects of hypothermia in the developing brain, where a massive amount of neurogenesis occurs, remain unclear. We investigated the proliferation of neural progenitor cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats in a severe hypothermic environment. The rat pups were divided into two groups, a hypothermia group (30 degrees C: n=10) and a normothermia group (37 degrees C: n=10). After the pups were placed for 21 h in each environment, 100 mg/kg/day of BrdU was injected intraperitoneally to label dividing cells, and then the pups were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the subventricular zone of the periventricle and the subgranular zone of the dentate gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased in number in the dentate gyrus, but not in the periventricular region. Thus, the severe hypothermic environment induced a decrease of neurogenesis in the neonatal rat. These observations are noteworthy regarding clinical hypothermia therapy following cerebral hypoxic ischemic injury during the perinatal period.     

Myocardial metastasis from renal cell carcinoma treated with sorafenib

We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.     

Free air on CT and the risk of peritonitis in peritoneal dialysis patients: a retrospective study

Background: Intra-abdominal free air is found frequently in patients undergoing peritoneal dialysis (PD). Some studies have investigated an association between intra-abdominal free air and peritonitis in PD patients. However, most used chest X-rays, which are of limited sensitivity, and the association was not made clear. We conducted a retrospective study of the association between peritonitis and intra-abdominal free air using computed tomography. Methods: The presence and volume of free air, and its relationship with other variables, were assessed on review of routine examinations in 108 patients. Correlations between the presence of free air and age, duration of PD, continuous ambulatory versus automated PD, presence or absence of a person who assisted in bag changes, exit-site infection, tunnel infection and peritonitis were assessed. Results: Free air was detected in 29 patients (27.1%). The prevalence of peritonitis was higher in the free air (+) group than in the free air (?) group: 1/40.2 patient-months for free air (+) versus 1/96.9 patient-months for free air (?). The risk ratio of free air for peritonitis was 2.41 (95% confidence interval: 2.28–2.55) and was similar when corrected for age, gender, albumin, diabetes mellitus and body mass index. Conclusion: Free air is an independent risk factor for peritonitis in PD patients. This suggests that bag change procedures should be re-evaluated, and patients re-educated, when necessary.     

Successful Combination Therapy of Radical Liver Resection With 5-Fluorouracil/leucovorin,Oxaliplatin, Plus Bevacizumab for Ascending Colon Cancer With Pulmonary and 43 Liver Metastases: Report of a Case

At the time of diagnosis, 20% to 25% of patients with colorectal cancer already have liver metastases, the presence of which is a most important prognostic factor. A 64-year-old man was admitted to our hospital for investigation of anemia and multiple liver tumors. Examinations revealed ascending colon carcinoma with more than 40 liver metastases and 2 lung metastases. We performed right hemicolectomy with lymph node dissection, which was followed by 5-fluorouracil/leucovorin, oxaliplatin, plus bevacizumab (FOLFOX-BV). After 4 courses of chemotherapy, the lung metastases were in complete remission and the liver metastases had shrunk. We suggested the option of radical liver resection, but the patient declined initially as he had not suffered any severe side effects of FOLFOX-BV. After 23 courses of the chemotherapy, he agreed to undergo hepatectomy. We performed extended right lobectomy with partial left and caudal lobe resection. All of the macroscopic metastatic lesions were resected. Histopathologically, viable cancer cells were recognized in 7 of the 43 liver metastatic lesions. Postoperatively, FOLFOX-BV was restarted and continued for 10 months. At the time of writing, 15 months after the hepatectomy, the patient was well without evidence of recurrence of the cancer.     

Ability of diffusion-weighted imaging for the differential diagnosis between chronic expanding hematomas and malignant soft tissue tumors

Purpose

To evaluate the potential of diffusion‐weighted imaging (DWI) in distinguishing chronic expanding hematomas (CEHs) from malignant soft tissue tumors.

Materials and Methods

We performed conventional MRI and DWI of six CEHs and 31 malignant soft tissue tumors from 37 patients seen between May 2000 and November 2006. DWI was obtained with a single‐shot echo‐planar imaging (EPI) sequence using a 1.5T MR imager. The mean apparent diffusion coefficient (ADC) value was also calculated. We evaluated MRI findings of CEHs and compared ADC value of CEHs with malignant soft tissue tumors.

Results

On conventional MRI, two of six CEHs were difficult to differentiate from malignant soft tissue tumors based on imaging findings. The mean ADC value of CEHs and malignant soft tissue tumors was 1.55 ± 0.121 × 10^?3 mm²/sec and 0.92 ± 0.139 × 10^?3 mm²/sec (mean ± SD), respectively. The mean ADC value of CEHs was significantly higher than that of malignant soft tissue tumors (P < 0.01). There was no overlap in the minimum ADC values among CEHs and malignant soft tissue tumors.

Conclusion

DWI is useful for differentiating between CEHs and malignant soft tissue tumors. J. Magn. Reson. Imaging 2008;28:1195–1200. © 2008 Wiley‐Liss, Inc.