Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics.

Cutaneous adnexal tumors are neoplasms that arise from skin appendages. Their morphologic diversity and phenotypic variability with rare progression to malignancy make them difficult to diagnose and classify, and there is currently no established treatment strategy. To overcome these difficulties, this study investigated the transcription factor SOX9 expression, morphology, and genetics of skin adnexal tumors for understanding their biology, especially their histogenesis. We showed that cutaneous adnexal tumors and their nontumor counterparts of skin and appendages exhibit expression patterns similar to that of SOX9. Its expression intensity and pattern, as well as histopathologic evaluation of tumors, were analyzed using digital images of 69 normal skin adnexal 9-type organs and 185 skin adnexal 29-type tumors as references. It was possible to distinguish basal cell carcinoma from squamous cell carcinoma, sebaceous carcinoma, and pilomatrixoma with significant differences, along with porocarcinoma from squamous cell carcinoma. Furthermore, unsupervised machine learning "computational pathology" was used to derive a multiregion whole-exome sequencing fusion method termed "genocomputed pathology." The genocomputed pathology of three representable adnexal carcinomas (porocarcinoma, hidradenocarcinoma, and spiradenocarcinoma) was evaluated for total nine cases. We showed that there was more heterogeneity than expected within the tumors as well as the coexistence of components lacking driver fusion genes. The presence or absence of potential driver genes, such as PIK3CA, YAP1, and PTEN, in each region was identified, highlighting a therapeutic strategy for cutaneous adnexal carcinoma encompassing heterogeneous tumors.

Postoperative acute multiple organ failure after hepatectomy in a Nigerian male with sickle cell trait: a case report.

BACKGROUND: Sickle cell disease (SCD) is a monogenic disease characterized by sickle hemoglobin (HbS). Patients homozygous for HbS experience symptoms resulting from sickled erythrocytes no later than adolescence. However, heterozygous HbS carriers, or those with the so-called sickle cell trait (SCT), may undergo surgery without their hemoglobinopathy being known. CASE PRESENTATION: A 53-year-old Nigerian male with hepatitis C infection underwent radiofrequency ablation therapy for multiple hepatocellular carcinomas (HCCs) 17 months prior. Follow-up computed tomography (CT) revealed a solitary tumor (3.2 cm) in the medial section of the cirrhotic liver. The Child-Pugh score was five, and the indocyanine green retention rate at 15 min was 17.4%. The nontumorous liver of the medial section accounted for 10% of the total liver volume according to CT volumetry. With the diagnosis of recurrent HCC, left medial sectionectomy was performed under intermittent blood flow occlusion by Pringle's maneuver. Intraoperative ultrasonography confirmed that hepatic blood flow had been preserved after hepatectomy. However, laboratory tests on postoperative day (POD) 1 revealed severe liver damage: aspartate aminotransferase 9250 IU/L, alanine aminotransferase 6120 IU/L, total bilirubin 2.8 mg/dL, and prothrombin time% 20.9%. The patient's renal and respiratory functions also deteriorated; therefore, continuous hemodiafiltration and plasma exchange were initiated under mechanical ventilation. Whole-body contrast-enhanced CT showed no apparent ischemia of the remnant liver, but diffuse cerebral infarction was detected. Despite intensive treatments, he died of multiple organ failure on POD 20. The pathological examination of the resected specimen revealed that the intrahepatic peripheral vessels were occluded by sickled erythrocytes. Additionally, chromatographic analysis of hemoglobin detected the presence of abnormal hemoglobin, although microscopic examination of the peripheral blood erythrocytes did not show morphological abnormalities. Based on these findings, we determined that he had SCT and developed vaso-occlusive crisis involving multiple organs just after hepatectomy. CONCLUSION: SCD is a rare disease in eastern Asia, but its prevalence is increasing globally. Surgeons should pay increased attention to this disease, especially when performing hepatectomy under blood flow occlusion.

Identification of novel heat shock-induced long non-coding RNA in human cells.

The heat-shock response is a crucial system for survival of organisms under heat stress. During heat-shock stress, gene expression is globally suppressed, but expression of some genes, such as chaperone genes, is selectively promoted. These selectively activated genes have critical roles in the heat-shock response, so it is necessary to discover heat-inducible genes to reveal the overall heat-shock response picture. The expression profiling of heat-inducible protein-coding genes has been well-studied, but that of non-coding genes remains unclear in mammalian systems. Here, we used RNA-seq analysis of heat shock-treated A549 cells to identify seven novel long non-coding RNAs that responded to heat shock. We focussed on CTD-2377D24.6 RNA, which is most significantly induced by heat shock, and found that the promoter region of CTD-2377D24.6 contains the binding site for transcription factor HSF1 (heat shock factor 1), which plays a central role in the heat-shock response. We confirmed that HSF1 knockdown cancelled the induction of CTD-2377D24.6 RNA upon heat shock. These results suggest that CTD-2377D24.6 RNA is a novel heat shock-inducible transcript that is transcribed by HSF1.

SMARCB-1 deficient squamous cell carcinoma of a mediastinal cyst.

SMARCB1-deficiency has been found in a variety of tumors. Here, we report a SMARCB1-deficient squamous cell carcinoma of a mediastinal cyst. A 53-year-old man was diagnosed with a cyst of the pericardial region in his twenties. As a symptom at this time, he complained of severe pain and dyspnea in the right chest. Following investigation using imaging and histological examination of the biopsy specimen, he was diagnosed with a SMARCB1 deficient malignant neoplasm. As tumor cells showed positive immunostaining for p40 and CK5/6, the immunophenotype of the tumor was consistent with squamous cell carcinoma (SCC). The patient died six months after initial presentation. The autopsy showed the most part of the tumor with anaplastic cytomorphology, loss of SMARCB1, diffusely positive immunostaining for pancytokeratin, and negative immunostaining for p40 and CK5/6. To our knowledge, this is the first report of SMARCB1-deficient SCC of mediastinal cyst.

Hypolipidemic Effect of the Autoclaved Extract Prepared from Pea (Pisum sativum L.) Pods In Vivo and In Vitro.

By autoclaving, we obtained a polyphenol and dietary fiber from pea (Pisum sativum L.) pods in parallel without acid or alkali treatment or organic solvent extraction. Rats fed a high-sucrose (HS) diet containing 3% autoclaved extract (AE) for 4 wk exhibited significantly lower serum triglyceride and total cholesterol levels than rats fed a HS diet. AE and soluble dietary fiber (SDF) from AE exhibited pancreatic lipase inhibitory activity at 13.3 mg/mL in vitro. AE and insoluble dietary fiber (IDF) from AE adsorbed cholesterol. In total, 30% and 10% of a cholesterol micelle were significantly adsorbed by 2,000 mg of AE and 100 mg of IDF from AE in 7 mL, respectively. The amount of bifidobacteria in the cecum of the AE group was significantly increased compared with that in the HS group. These results suggest that AE has hypolipidemic, bifidogenic potential.

Cloning and transcriptional expression of mouse mannosyltransferase IV/V cDNA, which is involved in the synthesis of lipid-linked oligosaccharides.

We cloned the mouse mannosyltransferase IV/V gene (mALG11) from FM3A cells by a bioinformatic approach. The ORF contained 1476 bp encoding 492 amino acids. The cloned mALG11 complemented the growth defect of the Saccharomyces cerevisiae ALG11Δ mutant. In addition, we detected a variant cDNA by alternate splicing that had an additional four-nucleotide ATGC insertion at base 276 of the ORF. Consequently the variant cDNA encoded a truncated protein with 92 amino acids, lacking the glycosyltransferase group-1 domain. The variant cDNA occurs in many mouse strains according to EST database searches. Moreover, we detected it in FM3A cDNA, but we did not detect any such variants in the human EST database or in HeLa cDNA, although human ALG11 (hALG11) genomic DNA has the same sequence around the intron-exon boundaries as those of mALG11 genomic DNA. Hence, we concluded that there is different transcriptional control mechanism between mALG11 and hALG11.

Remarkable expression in the colon adenocarcinoma of Hmat-Xa, a human mannosyltransferase-like gene, that is homologous to drosophila gene GC15914.

We cloned a novel human mannosyltransferase-like gene, designated Hmat-Xa, as a gene homologous to the Drosophila GC15914 gene encoding the 9QVXN0 protein: see "Project Report for FY2002 on the 'Construction of Libraries of Human Genes Participating in Glycosylation' project" 43-45 (2003), New Energy and Industrial Technology Development Organization (NEDO), NEDO and Research Association for Biotechnology, Tokyo, Japan (in Japanese). After that, the GTDC1 gene, as reported by Zhao et al., DNA Cell Biol., 23, 183-187 (2004), was found to be the same as the Hmat-Xa gene. Domain EXFGI/L/VX(2)L/VE in the Hmat-Xa protein, also present in both human mannosyltransferase II/III and mannosyltransferase IV/V, which are involved in the synthesis of lipid-linked oligosaccharides, and some bacterial mannosyltransferases. A real-time PCR study of Hmat-Xa mRNA expression in human normal and tumor multiple tissue cDNA identified its tissue-specific expression and its remarkable expression in colon adenocarcinoma as compared to the normal counterpart. Thus the elevated expression of Hmat-Xa might serve as a candidate marker for colon adenocarcinoma.