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Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)-based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders. [ABSTRACT FROM AUTHOR]

Background: We reported our experience of adenocarcinoma of sigmoid colon neovagina. Case presentation: A 67-year-old female with a history of neovagina construction for Rokitansky syndrome complained of vaginal bleeding. She had a mucinous adenocarcinoma at the anterior aspect of the neovagina. Her original surgery, using sigmoid colon to construct the artificial vagina, was 40 years ago Conclusions: This patient's case may contribute to our understanding of carcinogenesis in the colon. [ABSTRACT FROM AUTHOR]

The ubiquitous presence of inhibitory interneurons in the thalamus of primates contrasts with the sparsity of interneurons reported in mice. Here, we identify a larger than expected complexity and distribution of interneurons across the mouse thalamus, where all thalamic interneurons can be traced back to two developmental programmes: one specified in the midbrain and the other in the forebrain. Interneurons migrate to functionally distinct thalamocortical nuclei depending on their origin: the abundant, midbrain-derived class populates the first and higher order sensory thalamus while the rarer, forebrain-generated class is restricted to some higher order associative regions. We also observe that markers for the midbrain-born class are abundantly expressed throughout the thalamus of the New World monkey marmoset. These data therefore reveal that, despite the broad variability in interneuron density across mammalian species, the blueprint of the ontogenetic organisation of thalamic interneurons of larger-brained mammals exists and can be studied in mice. [ABSTRACT FROM AUTHOR]

Certain patients with early gastric cancer succumb to recurrent disease and cancer-associated complications. The key cause of recurrence is challenging to determine, since clinical blood markers that are able to predict the tumor properties of gastric cancer are limited. The present study investigated the fibrinogen concentration and neutrophil-lymphocyte ratio (NLR) in blood specimens from patients with gastric cancer, and assessed the clinical applicability of combining the fibrinogen concentration with the NLR (CFS-NLR) as a prognostic marker of gastric cancer. The present study consisted of 275 patients with gastric cancer, who were divided into three groups: Those possessing hyperfibrinogenemia (≥305 mg/dl) and a high NLR (≥2.34; CFS-NLR 2 group); those possessing either hyperfibrinogenemia or a high NLR (CFS-NLR 1 group); or those that possessed neither abnormality (CFS-NLR 0 group). The CFS-NLR was significantly associated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion and tumor stage (P<0.0001). The prognostic differences among the three groups were significant (P=0.0016). Therefore, the CFS-NLR may be a potentially useful blood marker for predicting tumor progression and the prognosis of patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC). However, because some patients respond well to CRT and others do not, it is important to be able to predict response to CRT before beginning treatment by using markers. Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions in centrosome maturation and chromosome segregation. In this study, we investigated the relationship between the expression of Aurora-A and the response to CRT in patients with ESCC. Methods: We immunohistochemically investigated the expression of Aurora-A in biopsy specimens of untreated primary tumors of 78 patients with ESCC and determined the relationship between Aurora-A levels and patient responses to CRT, which consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. Results: Tumors were judged as Aurora-A positive when more than 10% of the cancer cells displayed a distinct positive nuclear anti-Aurora-A immunoreaction by immunohistochemical evaluation. The tumors of 46 of 78 patients (58.9%) displayed positive expression of Aurora-A. In terms of clinical response the percentage of patients showing complete response (CR), incomplete response/stable disease of primary lesion (IR/SD), and progressive disease (PD) was 19.2, 69.2, and 11.5%, respectively. In terms of histological response the tumor grade of the 41 patients who underwent surgery was as follows: grade 1, 48.8%; grade 2, 29.2%; grade 3, 22.0%. CRT was effective for patients who had Aurora-A (+) tumors (clinically: P = 0.0003, histologically: P = 0.036). Conclusions: Our results suggest that Aurora-A expression in biopsy specimens of primary tumors is associated with CRT efficacy in patients with ESCC. Assessment of Aurora-A expression in biopsy specimens maybe useful for regarding the potential utility of CRT therapy for patients with ESCC before treatment. [ABSTRACT FROM AUTHOR]

Background The transcription factor nuclear factor (erythroid-2)-related factor 2 (Nrf2) was originally identified as a critical regulator of intracellular anti-oxidants and of phase II detoxification enzymes through its transcriptional up-regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2 protects not only normal cells but also cancer cells from cellular stress, and enhances cancer cell survival. Some studies have shown that Nrf2 expression in cancer patients has clinical significance. However, there has been no comprehensive analysis of the nuclear expression level of Nrf2 in gastrointestinal cancer cells. In this study we aimed to immunohistochemically evaluate the expression of Nrf2, and to assess its clinical significance in gastric cancer. Methods A total of 175 gastric cancer patients who received R0 gastrectomy with standard lymph node dissection were enrolled. We immunohistochemically evaluated Nrf2 expression in the paraffin-embedded surgically resected specimens of these 175 patients. Group differences were analyzed using the χ² test, Fisher's exact test, and the Mann-Whitney U test. Associations between Nrf2 expression and clinicopathological features, including clinical outcome, were assessed using univariate and multivariate analyses, and Kaplan-Meier curves with the log-rank test, respectively. Results Nrf2 immunoreactivity was predominantly identified in the nucleus of gastric cancer cells. Nrf2 positivity was closely associated with tumor size, tumor depth, lymph node metastases, lymphovascular invasion, histology and stage (p < 0.05 for all). A log-rank test indicated that the overall survival of the Nrf2-positive group was significantly poorer than that of the Nrf2-negative group (p < 0.01). And, positive Nrf2 expression was significantly associated with resistance to 5FU-based adjuvant chemotherapy (p = 0.024). Conclusions Nrf2 expression was positively associated with aggressive tumor behavior in gastric cancer. This result suggests that Nrf2 expression in gastric cancer is a potential indicator of worse prognosis. [ABSTRACT FROM AUTHOR]

Background Perioperative staging laparoscopy is a useful tool for the detection of occult peritoneal metastases in gastrointestinal cancers. This retrospective study aimed to determine the clinical value of staging laparoscopy for advanced or recurrent gastric cancer. Methods A total of 178 patients with advanced or recurred gastric cancer who underwent perioperative staging laparoscopy were enrolled. In the absence of peritoneal deposits (P1) and positive peritoneal cytology (CY1), gastrectomy with lymph node dissection was indicated with curative intent. If P1 or CY1 was detected intraoperatively, patients received intensive chemotherapy and laparoscopic surgical intervention. Results Curative gastrectomy was performed in 104 patients after confirmation of P0 and CY0 status. P1 or CY1 was detected for the first time in 23 (15%) patients. A total of 13 patients were converted from gastrectomy to intensive chemotherapy after detection of P1 or CY1. Additional laparoscopic interventions included insertion of intraperitoneal reservoir port in 54 patients, insertion of a metallic stent in five, ileostomy for colon stricture in six, jejunostomy in 19, and gastrojejunostomy in 16. Of eight patients treated with intensive chemotherapy who underwent R0 gastrectomy after second-look laparoscopy, five are currently free from recurrence of gastric cancer for 25.5 months. Conclusions Occult peritoneal dissemination was detected in about 14% in patients with tumors deeper than T2. Moreover, additional laparoscopic interventions can be utilized for P1 or CY1 patients. The excellent surgical outcomes of R0 gastrectomy after chemotherapy and second- look laparoscopy indicate that confirmation of P0 and CY0 status by staging laparoscopy is of value to determine treatment strategy in patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor (VEGF)-C and its receptor, VEGF receptor-3 (VEGFR-3), are key in the process of lymphangiogenesis. The present study immunohistochemically examined the expression of VEGF-C, VEGFR-3 and D2-40 in 119 patients with ESCC, and microlymphatic vessel density (MLVD) was calculated based on D2-40 expression counts. Positive expression of VEGF-C was found to correlate significantly with depth of tumor invasion, lymphatic invasion and lymph node metastasis (P<0.001, P<0.0001 and P<0.0001, respectively). Patients with deeper tumor invasion showed higher positivity of VEGFR-3 expression (P<0.05), while patients with lymph node metastasis showed higher MLVD (P<0.05). When patients were divided into three groups according to the expression of VEGF-C and VEGFR-3, patients with coexpression of VEGF-C and VEGFR-3 exhibited poorer prognosis and higher MLVD. The VEGF-C/VEGFR-3 axis is important in tumor lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Background: Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HAmediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear. Methods: We examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma. Results: Cancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01). Conclusion: Our results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid. [ABSTRACT FROM AUTHOR]