Eccrine Porocarcinoma Presenting with Unusual Clinical Manifestations: A Case Report and Review of the Literature

Eccrine porocarcinoma is a rare neoplasm that originates from the intraepidermal ductal portion of the eccrine sweat gland, and it usually occurs on the pre-existing lesion of benign eccine poroma. Its occurrence is more common in females and elderly persons. We present a case of a 44-year-old man who suffered from eccrine porocarcinoma, which developed on the right scrotum and pelvic area with metastases to the lung, adrenal gland, esophagus, ureter, and distant lymph nodes. Here we report on a unique case of eccrine porocarcinoma that developed primarily on the scrotum, which is an uncommon site, and showed rapid metastasis to the internal organs

Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Biomarker-driven targeted therapy, the practice of tailoring patients treatment to the expression/activity levels of disease-specific genes/proteins, remains challenging. For example, while the anti-ERBB2 monoclonal antibody, trastuzumab, was first developed using well-characterized, diverse in vitro breast cancer models (and is now a standard adjuvant therapy for ERBB2-positive breast cancer patients), trastuzumab approval for ERBB2-positive gastric cancer was largely based on preclinical studies of a single cell line, NCI-N87. Ensuing clinical trials revealed only modest patient efficacy, and many ERBB2-positive gastric cancer (GC) patients failed to respond at all (i.e., were inherently recalcitrant), or succumbed to acquired resistance. Method To assess mechanisms underlying GC insensitivity to ERBB2 therapies, we established a diverse panel of GC cells, differing in ERBB2 expression levels, for comprehensive in vitro and in vivo characterization. For higher throughput assays of ERBB2 DNA and protein levels, we compared the concordance of various laboratory quantification methods, including those of in vitro and in vivo genetic anomalies (FISH and SISH) and xenograft protein expression (Western blot vs. IHC), of both cell and xenograft (tissue-sectioned) microarrays. Results The biomarker assessment methods strongly agreed, as did correlation between RNA and protein expression. However, although ERBB2 genomic anomalies showed good in vitro vs. in vivo correlation, we observed striking differences in protein expression between cultured cells and mouse xenografts (even within the same GC cell type). Via our unique pathway analysis, we delineated a signaling network, in addition to specific pathways/biological processes, emanating from the ERBB2 signaling cascade, as a potential useful target of clinical treatment. Integrated analysis of public data from gastric tumors revealed frequent (10 – 20 %) amplification of the genes NFKBIE, PTK2, and PIK3CA, each of which resides in an ERBB2-derived subpathway network. Conclusion Our comprehensive bioinformatics analyses of highly heterogeneous cancer cells, combined with tumor omics profiles, can optimally characterize the expression patterns and activity of specific tumor biomarkers. Subsequent in vitro and in vivo validation, of specific disease biomarkers (using multiple methodologies), can improve prediction of patient stratification according to drug response or nonresponse

Rules for functional microRNA targeting

MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules for how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses. However, targeting rules reported in one study often fail to be reproduced in other studies and therefore the general rules for functional miRNA targeting remain elusive. In this review, we evaluate previously-reported miRNA targeting rules and discuss the biological impact of the functional miRNAs on gene-regulatory networks as well as the future direction of miRNA targeting research. © 2017 by the The Korean Society for Biochemistry and Molecular Biology

Postinflammatory hyperpigmentation associated with treatment of solar lentigines using a Q-Switched 532-nm Nd: YAG laser: a multicenter survey

Purpose: To characterize the risk factors of Korean patients for postinflammatory hyperpigmentation (PIH) during treatment of solar lentigines using a Q-switched 532-nm Nd: YAG (QS 532 NY) laser. Materials and Methods: The present retrospective multicenter study was conducted at the dermatology clinics of five tertiary hospitals in Korea. Between October 2007 and January 2013, 516 patients were enrolled and reviewed for clinical features and factors associated with PIH. Results: The overall incidence of PIH was 20.3%. We demonstrated that patients with erythematous lentigines presented with PIH more frequently compared with those without erythematous lentigines. Among several coexisting conditions, facial diffuse dyschromia was significantly associated with PIH. Furthermore, PIH occurred more frequently in patients with invisible pores and velvety skin. However, age, sex, Fitzpatrick skin’s phototype and season of treatment showed little association with PIH. Conclusions: When a QS 532 NY laser is used to treat individuals with erythematous lentigines, invisible pores and velvety skin, and facial diffuse dyschromia, clinicians should be cautious and consider preventive measures

The regulatory impact of RNA-binding proteins on microRNA targeting

© 2021, The Author(s).Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.11Nsciescopu

Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research

<div><p>Backgrounds</p><p>Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors.</p><p>Methods</p><p>Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually.</p><p>Findings</p><p>Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8–66.7] months).</p><p>Conclusions</p><p>Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.</p></div

Comparison of clinical features of early resumers and late resumers of TNF inhibitor in AS patients who experienced active tuberculosis infection.

<p>Comparison of clinical features of early resumers and late resumers of TNF inhibitor in AS patients who experienced active tuberculosis infection.</p