Nuclear accumulation of beta-catenin without an additional somatic mutation in coding region of the APC gene in hepatoblastoma from a familial adenomatous polyposis patient

The APC (adenomatous polyposis coli) gene status in a familial adenomatous polyposis (FAP) patient who developed hepatoblastoma was analyzed by the yeast color assay. Although a single base insertion at codon 462 resulting in truncation of its product was documented in hepatoblastoma cells, no additional somatic mutation was detectable in the whole coding sequence of the APC gene. The nuclear accumulation of beta-catenin without mutation in the exons 2-4 of the beta-catenin gene, however, was observed in the tumor cells by immunohistochemistry. The similar nuclear accumulation of beta-catenin without an additional somatic mutation in its gene, in the absence of somatic mutation in cluster region of the APC gene, has been previously reported in the single FAP case. Moreover, review in the hepatoblastoma cases in the FAP families showed a relatively later onset of the disease when compared with the sporadic cases. These observations suggest that accumulation of beta-catenin without an additional somatic mutation in the APC gene might be a possible mechanism for tumorigenesis of hepatoblastoma in the FAP families.     

Effect of type I growth factor receptor tyrosine kinase inhibitors on phosphorylation and transactivation activity of the androgen receptor in prostate cancer cells: Ligand-independent activation of the N-terminal domain of the androgen receptor

Although there have been several studies suggesting the involvement of growth factor receptor tyrosine kinases in ligand-independent activation of the androgen receptor (AR) and progression of prostate cancer, limited studies have been reported actually showing the enhancement of phosphorylation of the AR in vivo in response to growth factors or activation of their receptors in prostate cancer cells. In this study, we have demonstrated that overexpression of HER2/Neu enhanced in vivo phosphorylation of the AR and MAP kinase in DU-145 cells, and that the HER2/Neu inhibitor TAK165 reduced the HER2/Neu-enhanced phosphorylated AR and MAP kinase, indicating that the MAP kinase pathway seems to be involved in the phosphorylation of the AR by HER2/Neu. Both HER2/Neu inhibitor TAK165 and EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) successfully reduced the HER2/Neu-induced transactivation activity of the AR in PC-3 and DU-145 cells, suggesting that these inhibitors are possible therapeutic drugs for patients with hormone-refractory prostate cancer. The transactivation activity of the AF-1+DBD of the AR was enhanced by HER2/Neu overexpression while that of the AF-2+DBD was not, demonstrating that the enhancement of the AR activity by HER2/Neu was mainly mediated through the AF-1 of the AR.     

A case of sclerosing hemangioma surrounded by emphysematous change

A 44-year-old woman presented with high-grade fever. Chest radiography showed a 30 mm solitary pulmonary mass in the left lower lobe. Chest CT revealed a well-defined solid mass in the left lower lobe. On contrast-enhanced CT, the mass showed homogeneity and mild enhancement. There was an emphysematous portion in the surrounding lung parenchyma. The patient underwent partial lobectomy of the left lower lobe. The final diagnosis of sclerosing hemangioma with abundant vasculature was confirmed pathologically. Pulmonary sclerosing hemangioma is a rare benign neoplasm. Some cases have been reported in which sclerosing hemangioma is surrounded by air spaces. We suggest that the air spaces around the tumor were formed by not only peritumoral bleeding but also a check-valve effect of the compressed bronchus.     

Screening program of prostate cancer at Tokai University Hospital: characterization of prostate-specific antigen measurement

A total of 67,214 men participated in screening for prostate cancer (PC) using serum prostate-specific antigen (PSA) from April 1996 to March 2003 at Tokai University Hospital. In 3.5% (2330 / 67,214) of the men, an elevated PSA level (> 4.0 ng/ml) was found and 68.1% (1586/2330) of these subjects were examined at our Urological Outpatient Clinic. Re-testing of PSA showed that 8.4% (133/1586) had a normal level. Needle biopsy of the prostate was performed in 45.2% (633/1453) of the remaining men. As a result, 142 PCs were found and the detection rate was 0.2% (142 / 67,214). The age of the patients with PC was over 50 years. During this period, 135 individuals with voiding dysfunction were also diagnosed as having PC. Comparison of the patients detected by screening with those found at the outpatient clinic revealed significant differences of the age (64.8 vs. 71.9 years, p < 0.0001), serum PSA level (14.6 vs. 154.9 ng/ml, p < 0.0001), and clinical stage (p < 0.0001). In conclusion, a health screening program that includes serum PSA testing is useful for detection of PC at an earlier stage and in younger individuals. We recommend that all men aged 50 years or older undergo testing for PSA to detect PC at an early stage.     

Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector

Considerable attention has recently been paid to the application of chemokines to cancer immunotherapy because of their chemotactic affinity for a variety of immune cells and because several chemokines are strongly angiostatic. In the present study, the recombinant adenovirus vectors encoding chemokine CCL19 or XCL1 in an E1 cassette (AdRGD-mCCL19 and AdRGD-mXCL1) were developed. The constructed fiber-mutant adenovirus vector, which contained the integrin-targeting Arg-Gly-Asp (RGD) sequence in the fiber knob, notably enhanced the transfection efficiency to OV-HM ovarian carcinoma cells compared to that induced by conventional adenovirus vector. The results of an in vitro chemotaxis assay for chemokine-encoding vector demonstrated that both AdRGD-mCCL19 and AdRGD-mXCL1 could induce the migration of cells expressing specific chemokine receptors. Of the two chemokine-encoding vectors evaluated in vivo, AdRGD-mCCL19 showed significant tumor-suppressive activity in B6C3F1 mice via transduction into OV-HM cells, whereas XCL1 did not exhibit any notable anti-tumor effects, suggesting that CCL19 may be a candidate for cancer immunotherapy.     

Optical Coherence Tomography Before and After Vitrectomy with Internal Limiting Membrane Removal in a Child with Optic Disc Pit Maculopathy

Background

The pathogenesis of optic disc pit maculopathy is still unknown, although recent optical coherence tomographic (OCT) analyses have made a great contribution to clarifying its morphological appearance. The best treatment for this disease is also controversial.

Case

We report on a 7-year-old girl with optic disc pit maculopathy associated with a separation of the internal limiting membrane (ILM) near the optic disc.

Observations

The OCT images before treatment showed a conduit from the perineural space to the schisislike separation of the sensory retina with a dome-shaped separation of the ILM. A serous detachment (SD) in the macula, centered on the fovea, was also present. In OCT images after laser photocoagulation, the conduit appeared to be closed, but the SD was still present. Vitrectomy with ILM removal and gas tamponade resulted in a marked reduction of the SD in the macular area. Focal macular electroretinograms and visual acuity demonstrated a recovery of macular function.

Conclusion

The dome-shaped separation of the ILM suggested that the vitreous might be exerting a tractional force on the optic disc pit, and vitrectomy with ILM peeling released the traction on the optic disc pit. Jpn J Ophthalmol 2005;49:411–413 © Japanese Ophthalmological Society 2005     

Assessment of contractile response to dobutamine stress by means of ECG-gated myocardial SPECT: Comparison with myocardial perfusion and fatty acid metabolism

The present study assessed left ventricular performance during dobutamine stress measured using gated SPECT, and compared the results to myocardial perfusion and fatty acid metabolism. METHODS: Thirty-six patients with myocardial infarction given (99m)Tc-sestamibi or (99m)Tc-tetrofosmin were examined by gated SPECT at rest and during dobutamine stress (4-20 microg x kg(-1) x min(-1)). After acquiring data at the highest dose, 201TlCl was injected and dual-isotope SPECT was performed to assess myocardial ischemia. Thirty of 36 patients also underwent myocardial SPECT with 123I-BMIPP. Regional wall motion changes during dobutamine infusion were determined from the gated SPECT data and classified as: (1) Improvement, (2) Worsening, (3) No change, and (4) Biphasic response. For myocardial segments of each infarct area, stress 201Tl, rest (99m)Tc and (123)I-BMIPP uptakes were graded on a five-point scoring system of defects from 0 (normal) to 4 (grossly defective). RESULTS: Rest 99mTc defect score index (DSI) in No change area was significantly higher than that in Biphasic area. The ADSI (stress 201Tl - rest (99m)Tc) in Biphasic area was significantly higher than those in Improvement and No change areas. The deltaDSI (BMIPP - (99m)Tc) in Worsening area tended to be higher than that in No Change area. Conclusions: Regional contractile response to dobutamine stress analyzed by gated SPECT showed that the response in-myocardial infarct areas could be classified by rest and stress myocardial perfusion and BMIPP accumulation.     

Parasagittal meningioma en plaque with extracranial extension presenting diffuse massive hyperostosis of the skull

BACKGROUND: We describe a case of convexity meningioma en plaque (MEP) invading the skull and scalp with diffuse massive hyperostosis, presenting striking radiological findings. CASE DESCRIPTION: A 48-year-old woman was admitted to our hospital with headache, general fatigue, diplopia, and blurred vision. A skull X-ray film, computed tomography (CT), and 3-dimensional CT demonstrated diffuse significant hyperostosis and sclerosis in the cranial vault. Magnetic resonance (MR) imaging revealed a frontoparietal, well-enhanced extra-axial mass lesion, which is compatible with findings of MEP. The tumor was partially resected. Histological examination revealed massive tumor invasion into the dura mater, hyperostotic skull, and scalp. CONCLUSION: Hyperostosis is frequently observed in MEP, although there has been no report of a case of MEP such as ours demonstrating diffuse tumor extension and diffuse hyperostosis. Analyzing the CT finding of hyperostotic bone is useful for differentiation of MEP from other diseases that include a hyperostotic condition.     

Radio-guided brain tumorectomy using a gamma detecting probe and a mobile solid-state gamma camera

BACKGROUND: We herein report a technique to distinguish brain tumors from normal brain tissue during surgery using a gamma probe and a solid-state mobile gamma camera after (99m)Tc-hexakis-2-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) is administered to patients immediately before operation. METHODS: We examined 13 patients with brain tumors. Before the operation, (99m)Tc-MIBI single photon emission computed tomography (SPECT) was performed to assess accumulation in the tumors. On the day of the operation, (99m)Tc-MIBI was administered intravenously and craniotomy for tumor resection was performed. During the operation, the tumor was localized with a gamma probe and preremoval scintigraphy images were taken with a mobile gamma camera. After tumor resection was completed, residual tumors were confirmed using it again. We compared accumulation found in the preoperative SPECT images and intraoperative scintigraphy images, performed a histologic examination of adjacent tissues, and measured the dose the personnel was exposed to per operation. RESULTS: In all patients, tumors were confirmed by a gamma probe and scintigraphy during the operation. Intraoperative accumulation in tumors was significantly related to accumulation found in the preoperative (99m)Tc-MIBI SPECT images. In 9 out of 13 patients, accumulation disappeared in the postremoval scintigraphy images, and no tumor tissue was found by histologic examination. Residual tumor tissue was found in 4 patients. Average exposure of the personnel per operation was 22.9 +/- 4.0 microSv. CONCLUSION: Resection of brain tumors with a gamma probe and a mobile gamma camera was very useful since the area to be removed was easily identified and residual tumors could be detected.     

Di-(2-ethylhexyl) phthalate induces severe aspermatogenesis in mice, however, subsequent antioxidant vitamins supplementation accelerates regeneration of the seminiferous epithelium

Di-(2-ethylhexyl) phthalate (DEHP), now regarded as an endocrine disruptor, can experimentally induce spermatogenic disturbance in laboratory animals. Our previous study demonstrated that antioxidant vitamins (vitamins C and E) supplementation during DEHP-treatment significantly protected the rat seminiferous epithelium from DEHP-gonadotoxicity. In the present study, we gave these antioxidant vitamins to mice already having fully developed aspermatogenesis because of DEHP to determine whether or not the vitamins can cure the injured seminiferous epithelium. CD-1 male mice were fed on a DEHP-containing diet for 15 days and then fed on the DEHP-free normal diet with or without supplementation of vitamins C and E in drinking water for another 50 days. The results showed that severe aspermatogenesis was induced by the DEHP-treatment but that the damaged seminiferous epithelium spontaneously recovered whether the vitamins were provided or not. This indicates that the DEHP-induced aspermatogenesis was reversible. However, the supplementation of antioxidant vitamins significantly accelerated regeneration of the injured seminiferous epithelium, suggesting that the vitamins have a therapeutic effect on DEHP-induced aspermatogenesis.