The Reverse-Direction Method Links Mass Experimental Data to Human Diseases

Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin–epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.     

Infusion of growth hormone into the hippocampus induces molecular and behavioral responses in mice

Growth hormone (GH) has been implicated in a variety of brain functions, including neural development, cognition, and neuroprotection. The biological effects of GH are known to rely on the binding of GH to the GH receptor (GHR), yet the resulting signals in the brain remain poorly understood. The present study investigated the effects of hippocampal infusions of recombinant GH and a GHR antagonist on the expression of immediate early genes (IEGs) and behavioral responses in mice. The infusions induced differential expression of Arc, Nr4a1, and Npas4 mRNAs among the IEGs. The infusions also elicited differential behavioral responses, such as varied levels of spontaneous locomotion, self-grooming, and frequency of access to the corner fields in the open-field test. Polynomial regression analyses and canonical discriminant analyses between gene expression and behavioral changes demonstrated that the expression level of Arc mRNA was strongly correlated with locomotor activity level (r = 0.71 and 0.92 on days 8 and 10, respectively) and that the correlation was completely discriminable between drugs (error rate = 0 %). This analysis also revealed that a decrease in Npas4 mRNA was negatively correlated with the number of corner accesses (r = ?0.63) and that this correlation was partially discriminable between drugs (error rate = 16.67 %). Taken together, these results suggest that the GH–GHR complex modulates Arc and Npas4 signaling, which affects spontaneous locomotor and exploratory behaviors.     

Biliary adenofibroma with ominous features of imminent malignant changes

Biliary adenofibroma (BAF) is a rare, benign liver tumor. Herein, we report a case of BAF with histological features of imminent malignant changes. Ultrasound and CT revealed a solid 2.5-cm mass in the right liver lobe. The patient was asymptomatic and had no past medical history including liver disease. A general examination that included the abdomen and the laboratory data were normal. Because of the increase of its size, this tumor was surgically resected. Grossly, a 3.5-cm nodular mass abutted on the hepatic capsule was found, and its cut surface showed a well-circumscribed, whitish, and firm lesion that showed microcystic changes in the periphery and solid changes in the central parts. Histologically, the tumor showed a proliferation of tubulocystic structures embedded in a fibrous stroma. Microcysts were prevalent in the periphery, while tubular components with abundant fibrous stroma were in the central parts. The tubules were variably dilated and branched. This case closely resembled the previously reported cases of BAF, except that there were complicated papillary projections with fine fibrovascular cores in some of the microcysts and that the epithelial component in papillary projections showed dysplastic changes and increased cellular proliferative activities, implicating ominous features of imminent malignant changes. These dysplastic and papillary changes may be an intermediate lesion leading to malignancy, which have occasionally been reported in BAF.     

Influence of preoperative dental procedures on the prognosis of patients with squamous cell carcinoma of the gingiva

Our aim was to investigate the prognosis of patients with squamous cell carcinoma (SCC) of the gingiva who had preoperative dental operations. We studied 102 patients who were being operated on for SCC of the gingiva with special reference to the effects of preoperative dental operations on the prognosis. Twenty-six patients had dental procedures such as tooth extraction, or incision, or curettage before they visited our hospital, while the remaining 76 had no such interventions. The percentage of patients with advanced T stage disease (T3 or T4) was higher among those who had interventions (17/26, 65%) than among those who had not (35/76, 46%). The difference was not significant. Histopathologically invaded nodes were detected in half the patients in the intervention group (13/26), while they were found in only 18/76 (24%) of those in the no intervention group (p < 0.02). The incidence of nodal metastases with extranodal spread was significantly higher in the intervention group than in the no intervention group (p < 0.05), and those in the intervention group were more likely to develop distant metastases than those in the other group (p < 0.001). The 5-year survival in the two groups was 65% and 92%, respectively (p < 0.01). Preoperative dental operations such as tooth extraction, incision, or curettage possibly lead to regional and distant metastases and therefore a poor prognosis in patients with SCC of the gingiva.