Aberrant expression of human ortholog of mammalian enabled (hMena) in human colorectal carcinomas: implications for its role in tumor progression.

The human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoprotein (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. Increasing evidence suggests that hMena over-expression is involved in human breast cancers, whereas the significance of hMena expression in colorectal carcinomas remains to be elucidated. In this study, we assessed the relative mRNA level of hMena using real-time PCR, showing that there is a statistically significant increase of hMena transcripts in matched human colorectal carcinomas and adjacent non-neoplastic colorectal epithelium (n=6, P=0.046). We also performed immunohistochemical analysis of the expression of hMena protein in 50 cases of paraffin-embedded archival colorectal tissues, and found that an elevated hMena expression is correlated to the cases with advanced TNM stages of colorectal carcinomas (P<0.001). On further inspection of immunohistochemical features of each specimen, we observed intensified hMena staining in the invasive front of colorectal carcinomas, especially in tumor budding, a transition from glandular structure to single or small clusters of cells at the invasive front. We demonstrated that there was a significantly increased hMena staining in the tumor budding as compared with more morphologically-differentiated areas of colorectal carcinomas, indicating that hMena over-expression may have a role in the initial steps of tumor invasion from primary sites. We performed in vitro motility assays to show that transient hMena transfection markedly enhanced the chemotactic/chemokinetic activity of HeLaS3 cells (P<0.001). Taken together, these results suggest that hMena over-expression is implicated in the progression of colorectal carcinomas by positively affecting the migratory phenotype of cancer cells.

Clinical utility of the normal database of 123I-iodoamphetamine brain perfusion single photon emission computed tomography for statistical analysis using computed tomography-based attenuation correction: a multicenter study.

OBJECTIVES: We have established a common normal database (NDB) with applicability in multicenter settings for the statistical analysis of brain perfusion single photon emission computed tomography (SPECT) with triple energy window scatter correction, computed tomography-based attenuation correction (CTAC), and spatial resolution compensation. This study aimed to compare the CTAC normal database (CTAC-NDB) with conventional normal databases for the statistical analysis of 123I-iodoamphetamine (123I-IMP) brain perfusion SPECT at three institutions and to assess the clinical efficiency of CTAC-NDB. METHODS: We recruited 45 patients (26 men and 19 women; mean age, 74.2 ± 3.9 years; Mini-Mental State Examination score, 19.8 ± 6.1) with Alzheimer's disease (AD, n = 26), dementia with Lewy bodies (DLB, n = 9), and mild cognitive impairment (n = 10) from three institutions. Three-dimensional stereotactic surface projection (3D-SSP) technique was used to analyze data obtained from the 123I-IMP brain perfusion SPECT images compared with both CTAC-NDB and conventional NDB. We visually assessed each 3D-SSP z score map to determine the changes in specific findings, such as AD/DLB pattern. Furthermore, the stereotactic extraction estimation analysis software was used to measure the regional z score severity and extent as a semiquantitative assessment. RESULTS: In the visual assessment, all cases exhibited clearer findings with CTAC-NDB than with conventional NDB in the parietotemporal association cortex as well as in the inferior temporal, frontal, and lateral occipital cortices. Contrarily, the findings from the medial cerebral regions, including the precuneus and the posterior cingulate, became indistinct in 71% of the cases and remained unchanged in 25% of the cases. In the semiquantitative analysis, a similar tendency was observed in the mean z score in the three institutions included in the study. CONCLUSION: Using the CTAC-NDB, the findings in the vicinity of the cranium became increasingly clear, whereas those in the medial surface of the brain became less defined or remained unchanged. These findings were confirmed via a semiquantitative analysis. Moreover, similar changes in the reduction pattern were observed in the three institutions. Therefore, the new database with CTAC might be applicable in other institutions. Data collected in this study may serve as a CTAC-NDB.

Richter's Type of Incarcerated Obturator Hernia that Presented with a Deep Femoral Abscess: An Autopsy Case Report.

BACKGROUND Richter's obturator hernia is a rare abdominal hernia that is difficult to diagnose. The purpose of this case report is to show an unusual presentation of a fatal Richter's obturator hernia that was accompanied by a femoral abscess. CASE REPORT An 89-year-old woman complained of sudden left coxalgia and a gait disorder but no abdominal symptoms. She had no history of trauma or surgery in the inguinal area. Twenty-three days after her first complaint of coxalgia, the patient was admitted in a coma with necrotizing fasciitis in the left inguinal area. The patient died of asystole due to hyperkalemia. During surveillance for the cause of death, a Richter's type of incarcerated obturator hernia was identified at autopsy. The incarcerated small intestine had penetrated into the left obturator foramen to form an abscess that extended into the deep femoral region. CONCLUSIONS Obturator hernia accompanied by femoral abscess is extremely rare, but it should be suspected when a patient with no history of trauma or surgery has a femoral abscess, even in the absence of abdominal symptoms.

Characteristics of high-energy neutrons estimated using the radioactive spallation products of Au at the 500-MeV neutron irradiation facility of KENS.

We carried out a shielding experiment of high-energy neutrons, generated from a tungsten target bombarded with primary 500-MeV protons at KENS, which penetrated through a concrete shield in the zero-degree direction. We propose a new method to evaluate the spectra of high-energy neutrons ranging from 8 to 500 MeV. Au foils were set in a concrete shield, and the reaction rates for 13 radionuclides produced by the spallation reactions on the Au targets were measured by radiochemical techniques. The experimental results were compared with those obtained by the MARS14 Monte-Carlo code. A good agreement (between them) was found for energies beyond 100 MeV. The profile of the neutron spectrum, ranging from 8 to 500 MeV, does not depend on the thickness of the concrete shield.

Anthropogenic radionuclides in the atmosphere observed at Tsukuba: characteristics of the radionuclides derived from Fukushima.

During a serious accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), a huge quantity of radionuclides was released into the atmosphere and ocean. We measured anthropogenic radionuclides in surface air at Tsukuba, about 170 km from the FDNPP. On March 15, 2011, we detected the radioactivity released from the Fukushima accident in air samples at Tsukuba. The major radionuclides that we observed were radioiodine ((131)I, (132)I, (133)I) and radiocesium ((134)Cs, (136)Cs, (137)Cs). This radioiodine consisted of gaseous and particulate forms; the percentage of particulate (131)I in the total (131)I ranged from 0 to 86%. The percentage of the particulate (131)I to the total (131)I increased on the arrival of the plumes from major emissions of the FDNPP. After activities of the radionuclides attained the maximum on March 15, 2011, the FDNPP-derived radionuclides decreased rapidly in surface air. The activity median aerodynamic diameter of (131)I-bearing particles was 0.7 µm, while those of (134)Cs- and (137)Cs-bearing particles were larger than 1 µm. Large variations of ratios of (131)I/(137)Cs, (132)Te/(137)Cs, and (99)Mo ((99m)Tc)/(137)Cs (all involving different elements) suggest that the behaviors of these radionuclides in the atmosphere, including the processes of their emission, differed each other.

Fragmented hyaluronan is an autocrine chemokinetic motility factor supported by the HAS2-HYAL2/CD44 system on the plasma membrane.

Hyaluronan (HA) is synthesized by HA synthase (HAS) 1, HAS2 and HAS3, and degraded by hyaluronidase (HYAL) 1 and HYAL2 in a CD44-dependent manner. HA and HYALs are intricately involved in tumor growth and metastasis. Random cell movement is generally described as chemokinesis, and represents an important step at the beginning of tumor cell liberation from the primary site. To investigate the roles of HAS2 and HYAL2/CD44 in cell motility, we examined HeLa-S3 cells showing spontaneous chemokinesis. HeLa-S3 cells expressed HAS2 and HAS3. siRNA-mediated knockdown of HAS2 decreased spontaneous chemokinesis of HeLa-S3 cells. Although HeLa-S3 cells secreted 50 ng/ml of high molecular weight (HMW)-HA (peak: 990 kDa) into the culture supernatant after 6 h of culture, exogenously added HMW-HA did not enhance spontaneous chemokinesis of the cells. These observations suggested that HeLa-S3 cells may have a self-degrading system for HA to regulate their spontaneous chemokinesis. To examine this possibility, we investigated the effects of siRNA-mediated knockdown of HYAL2 or CD44 on the spontaneous chemokinesis of HeLa-S3 cells. Knockdown of either molecule decreased the spontaneous chemokinesis of the cells. Low molecular weight (LMW)-HA (23 kDa) reversed the HYAL2 siRNA-mediated reduction in spontaneous chemokinesis of HeLa-S3 cells to the level in control cells stimulated with the same HA. These findings indicate that the HAS2-HYAL2/CD44 system may support spontaneous chemokinesis of human cancer cells through self-degradation of HMW-HA to produce LMW-HA by an autocrine mechanism. Consequently, our study may further expand our understanding of HA functions in cancer.

Overexpression of human ortholog of mammalian enabled (hMena) is associated with the expression of mutant p53 protein in human breast cancers.

The human ortholog of mammalian enabled (hMena), a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family, is an actin regulatory protein involved in the regulation of cell motility. Increasing evidence suggests that hMena overexpression is involved in human cancers, but the upstream events that influence the expression of hMena remain to be elucidated. In this study, we performed immunohistochemical analysis of the expression of hMena protein in paraffin-embedded archival tissues of infiltrating ductal carcinomas (IDCs) obtained from 52 cases. We found that elevated hMena expression is associated with larger tumor size (>2.5 cm, p<0.01), HER2 expression (p<0.05), p53 index (p<0.03) and Ki67 index (p<0.01), suggesting that hMena is a predictor of poor prognosis in IDCs. The histological characteristics of each specimen showed that hMena was overexpressed in the tumor cells at the invasive front of IDCs, indicating that hMena expression is at least partly mediated by tumor cell-matrix interactions. To explore the role of the absence of p53 function in hMena overexpression of IDCs, wild-type p53 cDNA was introduced into SW620 cells, which originally express mutant p53. In wild-type p53-transfected cells, hMena mRNA expression was decreased to 70% of the levels in mock transfected cells (p<0.01). In conclusion, our study indicates that hMena overexpression is involved in the progression of IDCs, and raises the possibility that wild-type p53 may suppress hMena expression.

A case report of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and literature review.

Osteoclast-like giant cell tumors rarely arise in the pancreas. Here we report the case of a 78-year-old woman who was diagnosed with a well-defined 3 cm multilocular mass in the pancreatic body by the use of ultrasonography, computed tomography and magnetic resonance imaging. The rim and the septa of the tumor were well enhanced. The distal pancreas was removed with the spleen and the peripancreatic lymph nodes. Macroscopically, the mass was composed predominantly of a multilocular cystic tumor filled with hemorrhagic necrosis, and partly composed of solid components. A histopathological study showed a proliferation of multinucleated osteoclast-like giant cells and spindle cells. Although the predominant tumor cells were strongly positive for vimentin and CD68 and negative for epithelial markers, there were some sparsely scattered cytokeratin-positive neoplastic glands. Seventeen months after surgery, the patient is still alive and has had no recurrence. Below we review 32 cases of osteoclast-like giant cell tumor of the pancreas that have been reported in English literature since 2000.

Human Mena associates with Rac1 small GTPase in glioblastoma cell lines.

Mammarian enabled (Mena), a member of the Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) family of proteins, has been implicated in cell motility through regulation of the actin cytoskeleton assembly, including lamellipodial protrusion. Rac1, a member of the Rho family GTPases, also plays a pivotal role in the formation of lamellipodia. Here we report that human Mena (hMena) colocalizes with Rac1 in lamellipodia, and using an unmixing assisted acceptor depletion fluorescence resonance energy transfer (u-adFRET) analysis that hMena associates with Rac1 in vivo in the glioblastoma cell line U251MG. Depletion of hMena by siRNA causes cells to be highly spread with the formation of lamellipodia. This cellular phenotype is canceled by introduction of a dominant negative form of Rac1. A Rac activity assay and FRET analysis showed that hMena knock-down cells increased the activation of Rac1 at the lamellipodia. These results suggest that hMena possesses properties which help to regulate the formation of lamellipodia through the modulation of the activity of Rac1.

Collision of advanced gastric adenocarcinoma and gastrointestinal stromal tumour: a case report.

We present a case of an 83-year-old female patient with a collision tumour of an advanced Borrmann type 4 gastric cancer and a large gastric gastrointestinal stromal tumour (GIST). According to the deformity of the gastric wall caused by the GIST, type 4 cancer was difficult to identify by oesophagogastroduodenoscopy (OGD). The patient died of progressive gastric cancer related disease. While the mechanism of histogenesis of the simultaneous adenocarcinoma and GIST remains to be determined, the present case suggests that gastric adenocarcinoma has a more adverse effect on prognosis than does GIST. Additionally, this case suggests that thorough inspection of GIST patients is required at the OGD and at the pathology facility, in order to avoid overlooking the underlying cancer.