A20 (TNFAIP3) Alterations in Primary Intestinal Diffuse Large B-cell Lymphoma

The gastrointestinal (GI) tract is the most frequently involved site of extranodal non-Hodgkin lymphomas, and diffuse large B-cell lymphoma (DLBCL) is the most common subtype occurring in the GI tract. TNFAIP3 (A20) genetic alterations were reported to be involved in DLBCL’s pathogenesis and a portion of GI-DLBCL cases harbor this alteration. However, the frequency and clinicopathological relations focusing on small and large intestinal DLBCL are unclear. Here, we examined A20 deletion and protein expression and analyzed the clinicopathological features of 52 cases of primary intestinal DLBCL. The most frequently involved site was the ileocecal region (75%), followed by small bowel (13.5%) and large intestine. Immunohistochemically, the ileocecal cases expressed BCL6 (p=0.027) and MUM1 (p=0.0001) significantly more frequently than the small intestinal cases. Six of 47 cases (13%) had A20 heterozygous deletion, whereas all 6 heterozygously deleted cases had detectable A20 protein expression. In summary, A20 abnormality was less prevalent among intestinal DLBCLs with some discordancy between gene deletion and protein expression. Although the A20 alteration status did not affect any clinicopathological characteristics in this series, further studies exploring alterations of A20 and other NF-κB components in primary intestinal DLBCL are needed

Diagnostic accuracy of frozen section biopsy for early gastric cancer extent during endoscopic submucosal dissection: a prospective study

Background Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. Methods We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as “neoplasia,” “negative for neoplasia,” or “indefinite for neoplasia,” and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. Results Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen’s kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837–0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. Conclusions Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD

Aberrant Methylation of p21 Gene in Lung Cancer and Malignant Pleural Mesothelioma

Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs

Endoscopic resection of pleomorphic adenoma

Background : An accessory parotid gland (APG) is a common anatomical structure that occurs in 10%–56% of individuals. Pleomorphic adenomas are the most common benign tumors of the APG, and their ideal treatment is surgical excision, although there is a risk for aesthetic disorders and facial nerve damage due to the site of origin. Moreover, despite being benign, these tumors are known to recur. Therefore, it is necessary to achieve both reliable excision and avoidance of facial nerve damage. Case presentation : We report a case of a 49-year-old Japanese man with a mass in his left cheek. The lesion was diagnosed as a benign salivary gland tumor derived from the APG by computed tomography imaging, magnetic resonance imaging and fine needle aspiration cytology. We resected the tumor using modified high submandibular incision under the endoscopic-assisted field of view. Discussion and Conclusions : The tumor was less invasive and reliably resected using an endoscope. In surgical treatment, the endoscopic-assisted technique is very useful to achieve complete tumor resection and prevent relapse while avoiding serious complications due to surgical procedures

Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo

Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CTL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL in vivo by Epstein-Barr virus-specific iPSC-derived antigen-specific CTL, with iPSC-derived antigen-specific CTL persisting as central memory T cells in the mouse spleen for at least six months. The anti-tumor response is so strong that any concomitant effect of the programmed cell death 1 (PD-1) blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific iPSC-derived antigen-specific CTL contribute to a continuous anti-tumor effect and offer an effective salvage therapy for relapsed and refractory ENKL

Cucumber mosaic virus infection in Arabidopsis: A conditional mutualistic symbiont?

A cucumber mosaic virus isolate, named Ho [CMV(Ho)], was isolated from a symptomless Arabidopsis halleri field sample containing low virus titers. An analysis of CMV(Ho) RNA molecules indicated that the virus isolate, besides the usual cucumovirus tripartite RNA genome, additionally contained defective RNA3 molecules and a satellite RNA. To study the underlying mechanism of the persistent CMV(Ho) infection in perennial A. halleri, infectious cDNA clones were generated for all its genetic elements. CMV, which consists of synthetic transcripts from the infectious tripartite RNA genomes, and designated CMV(Ho)tr, multiplied in A. halleri and annual Arabidopsis thaliana Col-0 to a similar level as the virulent strain CMV(Y), but did not induce any symptoms in them. The response of Col-0 to a series of reassortant CMVs between CMV(Ho)tr and CMV(Y) suggested that the establishment of an asymptomatic phenotype of CMV(Ho) infection was due to the 2b gene of CMV RNA2, but not due to the presence of the defective RNA3 and satellite RNA. The accumulation of CMV(Ho) 2b protein tagged with the FLAG epitope (2b.Ho-FLAG) in 2b.Ho-FLAG-transformed Col-0 did not induce any symptoms, suggesting a 2b-dependent persistency of CMV(Ho)tr infection in Arabidopsis. The 2b protein interacted with Argonaute 4, which is known to regulate the cytosine methylation levels of host genomic DNA. Whole genomic bisulfite sequencing analysis of CMV(Ho)tr- and mock-inoculated Col-0 revealed that cytosine hypomethylation in the promoter regions of 82 genes, including two genes encoding transcriptional regulators (DOF1.7 and CBP1), was induced in response to CMV(Ho)tr infection. Moreover, the increased levels of hypomethylation in the promoter region of both genes, during CMV(Ho)tr infection, were correlated with the up- or down-regulation of their expression. Taken altogether, the results indicate that during persistent CMV(Ho) infection in Arabidopsis, host gene expression may be epigenetically modulated resulting from a 2b-mediated cytosine hypomethylation of host genomic DNA

The Tokyo Oldest Old Survey on Total Health (TOOTH): A longitudinal cohort study of multidimensional components of health and well-being

<p>Abstract</p> <p>Background</p> <p>With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study.</p> <p>Methods/Design</p> <p>For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors.</p> <p>Discussion</p> <p>Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.</p> <p>Trial Registration</p> <p>This study has been registered in the UMIN-Clinical Trial Registry (CTR), ID: UMIN000001842.</p