A novel prognostic biomarker for cutaneous malignant melanoma: red cell distribution width (RDW) to lymphocyte ratio

xlomafota13 shared this article with you from Inoreader A novel prognostic biomarker for cutaneous malignant melanoma: red cell distribution width (RDW) to lymphocyte ratio Via Melanoma Research - Published Ahead-of-Print It is well-known that inflammation plays a significant role in cancer formation and prognosis. Both lymphocyte count and red cell distribution width (RDW) has been used to predict prognosis in various cancers as an indicator of inflammation. Yet, the role of RDW-lymphocyte ratio (RLR) in determining prognosis is still unkn own. We aimed to determine the prognostic role of RLR in cutaneous malignant melanoma (MM). One hundred fifteen patients with MM were included in the study retrospectively. The relationship of the clinical-pathological data with overall survival (OS) and progression-free survival (PFS) was analyzed using Kaplan–Meier curves. The cut-off values of neutrophil to lymphocyte ratio, systemic immune-inflammation index (SII), prognostic nutritional index (PNI) and RLR were determined as 2, 487, 51.5 and 6.52, respectively. OS was significantly longer in the low SII, high PNI, low RLR group, while PFS was longer in groups with high PNI and low RLR. In univariate analysis, it was determined that PFS was significantly correlated with Eastern Cooperative Oncology Group (ECOG) performance, TNM stage, PNI and RLR. Moreover, in univariate analysis, a significant correlation was determined between OS and age, ECOG performance, TNM stage, adjuvant interferon, SII, PNI and RLR. In multivariate ana lysis, ECOG performance, TNM stage and RLR were determined as independent prognostic factors for PFS, while TNM stage and RLR were found to be independent prognostic factors for OS. RLR could be a novel prognostic marker for both PFS and OS in patients with cutaneous MM. Received 15 June 2021 Accepted 4 September 2021 Correspondence to Zekeriya Hannarici, Department Of Medical Oncology, Atatürk University Faculty of Medicine, Yakutiye, Erzurum 25100, Turkey, Tel: +905303768489; e-mail: hannarici@hotmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk factors in pediatric melanoma: a retrospective study of 39 cases

xlomafota13 shared this article with you from Inoreader Risk factors in pediatric melanoma: a retrospective study of 39 cases Via Melanoma Research - Published Ahead-of-Print Pediatric melanoma is a rare form of the tumor whose epidemiology is widely increasing thanks to the improvement of dermoscopic and anatomopathologic diagnostic techniques. Although it is a tumor of considerable interest in adults, little has been described about the pediatric field. The objective of our study was then to ident ify the possible risk factors for the development of melanoma in the pediatric population. We performed a retrospective study conducted in the Melanoma and Skin Cancer Unit and Unit of Dermatology (Livorno, Italy). We analyzed a population of 38 children under 21 years with a diagnosis of melanoma. This population was compared with a control population of 114 children followed up in our dermatologic clinic. From our combined univariate-multivariate statistics analysis, the number of nevi [regression coefficient (RC) of 1.04 and odds ratio (OR) of 2.8 confidence interval (Cl, 1.2–6.6)], and family history of melanoma [RC of 1.99 and OR of 7.3 (Cl, 2.3–22.7)] emerged as possible risk factors for the development of melanoma. The identification of these elements would allow the physician to carry out a more targeted preliminary assessment of the patient, potentially decisive in cases of diagnostic doubt of the lesion. Our study also lays the foundations for identifying those child ren who, despite not having received a diagnosis of melanoma on histologic examination, should be considered as patients susceptible to a focused follow-up, because of the presence of the risk factors that emerged from our research. Received 16 June 2021 Accepted 3 August 2021 Correspondence to Giovanni Bagnoni, MD, Melanoma and Skin Cancer Unit AVNO (Area Vasta Nord Ovest) and Unit of Dermatology, Specialist Surgery Area, Department Of General Surgery, Livorno Hospital, Viale Vittorio Alfieri 36, Livorno, LI 57124, Italy, Tel: +39 0586 223243; e-mail: giovanni.bagnoni@uslnordovest.toscana.it Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Assessment of estrogen receptor low positive status in breast cancer: Implications for pathologists and oncologists

xlomafota13 shared this article with you from Inoreader Assessment of estrogen receptor low positive status in breast cancer: Implications for pathologists and oncologists Via Cellular and Molecular Biology Histol Histopathol. 2021 Sep 29:18376. doi: 10.14670/HH-18-376. Online ahead of print. ABSTRACT Estrogen receptor (ER) status assessment by immunohistochemistry (IHC) is the gold standard test for the identification of patients with breast cancer who may benefit from endocrine therapy (ET). Whilst most ER+ breast cancers have a high IHC score, about 3% of cases display a low positivity, with 1% to 10% of cells being weakly stained. These tumors are generally classified within the luminal-like category; however, their risk profile seems to be more similar to that of ER-negative breast cancers. The decision on ET for patients with a diagnosis of ER-low breast cancer should be carefully considered in light of the risks and possible benefits of the treatment. Potential pitfalls hinder pathologists and oncologists from establishing an appropriate threshold for "low positivity". Furthermore, several pre-analytical and analytical variables mi ght trouble the pathological identification of these clinically challenging cases. In this review, we sought to discuss the adversities that can be accounted for the pathological identification of ER-low breast cancers in real-world clinical practice, and to provide practical suggestions for the perfect ER testing in light of the most updated recommendations and guidelines. PMID:34585734 | DOI:10.14670/HH-18-376 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of low-level laser intervention on dermatitis symptoms and cytokine changes in DNCB-induced atopy mouse model: A randomized controlled trial

xlomafota13 shared this article with you from Inoreader Effect of low-level laser intervention on dermatitis symptoms and cytokine changes in DNCB-induced atopy mouse model: A randomized controlled trial Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1196. doi: 10.3892/etm.2021.10630. Epub 2021 Aug 20. ABSTRACT The incidence of atopic dermatitis (AD) has recently increased due to various factors. Its prevalence is higher among children and teenagers than in other age groups. Numerous methods to treat AD are available, including light ray therapy, which has been proposed as an alternative therapy for the treatment of AD. The present study aimed to evaluate the curative mechanism and optimal energy level of energy irradiation from a low-level laser (LLL) toward AD. AD was induced in BALB/c mice with dinitrochlorobenzene (DNCB) solution. The mice were divided into six groups, including one normal control (n=8), one AD control (n=10) and four AD experimental groups with LLL irradiation at 2 J/cm2 (n=10), 4 J/cm2 (n=10), 6 J/cm2 (n=9) and 8 J/cm2 (n=10). Following AD induction, an LLL was applied to the four AD exp erimental groups for 2, 4, 6, and 8 min, for two weeks (14 times in total) at a wavelength of 650 nm and an output of 50 mW. The effects of irradiation on AD were evaluated using a scratch test, a clinical skin severity test, immunoglobulin-E (IgE) analysis and measurements of numerous cytokine levels, including interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-α, and interferon-γ (IFN-γ), tissue thickness and mast cell count. The results demonstrated that serum IgE level in all irradiated groups was significantly decreased compared with that of the AD control group, and IL-4 level was significantly decreased in all irradiated groups apart from the 8 J/cm2 LLL irradiated group. IL-6 and TNF-α levels were also significantly decreased in all irradiated groups. The results from histological analysis revealed diminished epidermal thickness and mast cell counts in irradiated mice compared with those mice in the AD control group. In summary, these findings suggested tha t LLL irradiation may alleviate symptoms of AD and may be useful for restoring cytokines levels and tissues features to normal levels. PMID:34584541 | PMC:PMC8422383 | DOI:10.3892/etm.2021.10630 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

AREL1 E3 ubiquitin ligase inhibits TNF-induced necroptosis via the ubiquitination of MTX2

xlomafota13 shared this article with you from Inoreader AREL1 E3 ubiquitin ligase inhibits TNF-induced necroptosis via the ubiquitination of MTX2 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1195. doi: 10.3892/etm.2021.10629. Epub 2021 Aug 20. ABSTRACT Previously, we reported on a novel anti-apoptotic E3 ubiquitin ligase, apoptosis-resistant E3 ubiquitin protein ligase 1 (AREL1), that ubiquitinates inhibitors of apoptosis proteins antagonists. The present study demonstrated that AREL1 ubiquitinated Metaxin 2 (MTX2), which was involved in TNF-induced necroptosis. MTX2 has been identified as a protein that belongs to the Metaxin family. It interacts with another Metaxin protein, Metaxin 1 (MTX1), which is localized in the outer membrane of mitochondria, and is involved in TNF-induced necroptosis. This study found that AREL1 interacted with MTX2, but not MTX1, while the amino-terminal domain of MTX2 interacted with MTX1, AREL1 interacted with the carboxyl-terminal domain of MTX2. Furthermore, AREL1 expression led to a decrease in the protein expression of MTX2, but not MTX1. However, a mutant form of AREL1, AREL1C790A, which is deficient for E3 activity, did not cause MTX2 degradation. Moreover, the protein levels of MTX2 were increased by AREL1 knockdown. Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. The expression of MTX2, together with MTX1, enhanced TNF-induced necroptosis. However, AREL1 inhibited necroptosis even in cells expressing Metaxin proteins. Therefore, these results suggested that the inhibition of AREL1-dependent ubiquitination of MTX2 could be beneficial to sensitize tumor cells to TNF-induced necroptosis. PMID:34584540 | PMC:PMC8422393 | DOI:10.3892/etm.2021.10629 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

hsa-miR-15b-5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis

xlomafota13 shared this article with you from Inoreader hsa-miR-15b-5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1208. doi: 10.3892/etm.2021.10642. Epub 2021 Aug 24. ABSTRACT A previous bioinformatic analysis from our group predicted that the interaction of microRNA (miRNA/miR)-15b with the acyl-CoA synthetase short chain family member 2 (ACSS2) gene was important for the development of abdominal aortic aneurysm (AAA). Apoptosis of aortic vascular smooth muscle cells (VSMCs) is a pathological feature of AAA. The present study aimed to explain the roles of miR-15b/ACSS2 in AAA by exploring their effects on the proliferation and apoptosis of aortic VSMCs. Human aortic VSMCs (T/G HA-VSMC cell line) were divided into six groups and were transfected with miR-15b-5p mimics, mimic negative control (NC), miR-15b-5p inhibitors, inhibitor NC, miR-15b-5p mimics+pcDNA3.1 and miR-15b-5p mimics+ACSS2-overexpessing vector. CCK-8 assay was used to determine cell proliferation. Annexin V-FITC/PI staining and flow cytometry assays were used to measure cell apoptosis. Dual-luciferase reporter assays were used to confirm the targeted relationship between miR-15b-5p and ACSS2. Reverse transcription-quantitative PCR and/or western blotting were used to examine the expression levels of miR-15b-5p, ACSS2 and prostaglandin-endoperoxide synthase 2 (PTGS2). Following transfection of T/G HA-VSMCs with mimics and inhibitors to respectively upregulate and downregulate miR-15b-5p, the results demonstrated that overexpression of miR-15b-5p inhibited cell proliferation and promoted cell apoptosis; silencing of miR-15b-5p obtained the opposite results. ACSS2 may be a direct target of miR-15b-5p, since the luciferase activity of a ACSS2 wild-type vector, but not that of a ACSS2 mutant reporter, was significantly inhibited by miR-15b-5p mimics compared with controls. Additionally, the expression levels of ACSS2 and its downstream gene PTGS2 were significantly reduced or increased following transfection with miR-15b-5p mimics or in hibitors, respectively. Furthermore, overexpression of ACSS2 reversed the antiproliferative and proapoptotic effects of miR-15b-5p mimics by blocking the production of PTGS2 protein. In conclusion, miR-15b-5p may promote the apoptosis and inhibit the proliferation of aortic VSMCs via targeting the ACSS2/PTGS2 axis. The present study provided preliminary evidence indicating that the miR-15b-5p/ACSS2/PTGS2 axis may be a potential target for the treatment of AAA. PMID:34584553 | PMC:PMC8422401 | DOI:10.3892/etm.2021.10642 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Leonurine protects against ulcerative colitis by alleviating inflammation and modulating intestinal microflora in mouse models

xlomafota13 shared this article with you from Inoreader Leonurine protects against ulcerative colitis by alleviating inflammation and modulating intestinal microflora in mouse models Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1199. doi: 10.3892/etm.2021.10633. Epub 2021 Aug 23. ABSTRACT Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the colon. The aim of the present study was to explore the effects of leonurine (YMJ) on inflammation and intestinal microflora in colonic tissues of a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Mice were randomly divided into control (n=5), DSS (n=5, treated with DSS) and DSS+YMJ (n=5, treated with DSS and YMJ) groups. Body weight was recorded, disease activity index (DAI) was calculated, and colon histopathology was evaluated using hematoxylin and eosin staining. Serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β levels were examined using ELISA. Expression levels of nuclear factor-κB (p65) and phosphorylated (p)-p65 were evaluated via western blotting. 16S ribosomal RNA was extracted from mouse feces. Composition or abundan ce changes of intestinal microflora were analyzed. The results indicated that YMJ treatment (DSS+YMJ group) significantly increased body weight, reduced DAI scores and increased colon length in UC mouse models compared with those in the DSS group (P<0.05). YMJ significantly reduced inflammatory infiltration, significantly decreased serum TNF-α, IL-6 and IL-1β levels (P<0.05) and significantly downregulated the p-p65/p65 ratio compared with the DSS group (P<0.05). YMJ increased the quantity of the intestinal flora and improved intestinal microflora diversity in the mice of the DSS group. Specifically, YMJ partly regulated intestinal microflora in feces, including a reduction of Bifidobacterium, and an increase in Parasutterella and Ackermania. In conclusion, YMJ improved disease outcomes of the UC mice, reduced the levels of serum inflammatory factors and increased the ratio of beneficial bacteria in the intestinal tract. PMID:34584544 | PMC:PMC8422400 | DOI:10.3892/etm.2021.10633 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.