JPM, Vol. 10, Pages 244: Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia

Alexandros G.Sfakianakis shared this article with you from Inoreader JPM, Vol. 10, Pages 244: Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia Μέσω Journal of Personalized Medicine JPM, Vol. 10, Pages 244: Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia Journal of Personalized Medicine doi: 10.3390/jpm10040244 Authors: Nerea Vega-Garcia Rocío Benito Elena Esperanza-Cebollada Marta Llop Cristina Robledo Clara Vicente-Garcés Javier Alonso Eva Barragán Guerau Fernández Jesús Hernández-Sánchez Marta Martín-Izquierdo Joan Maynou Alfredo Minguela Adrián Montaño Margarita Ortega Montserrat Torrebadell José Cervera Joaquín Sánchez Antonio Jiménez-Velasco Susana Riesco Jesús Hernández-Rivas Álvaro Lassaletta José Fernández Susana Rives José Dapena Manuel Ramírez Mireia Camós on behalf of the Group of Leukemia of the Spanish Society of Pediatric Hematology and Oncology (SEHOP) The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology's complexity, bioinformatics analysis, and the different available options difficult a broad consensus between different laboratories in its daily routine introduction. This collaborative study among Spanish centers was aimed to assess the feasibility, pros, and cons of our customized panel and other commercial alternatives of NGS-targeted approaches. The custom panel was tested in three different sequencing centers. We used the same samples to assess other commercial panels (OncomineTM Childhood Cancer Research Assay; Archer®FusionPlex® ALL, and Human Comprehensive Cancer Panel GeneRead Panel v2®). Overall, the panels showed a good performance in different centers and platforms, but each NGS approach presented some issues, as well as pros and cons. Moreover, a previous consensus on the analysis and reporting following international guidelines would be preferable to improve the concordance in results among centers. Our study shows the challenges posed by NGS methodology and the need to consider several aspects of the chosen NGS-targeted approach and reach a consensus before implementing it in daily practice. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

JPM, Vol. 10, Pages 246: Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer

Alexandros G.Sfakianakis shared this article with you from Inoreader JPM, Vol. 10, Pages 246: Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer Μέσω Journal of Personalized Medicine JPM, Vol. 10, Pages 246: Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer Journal of Personalized Medicine doi: 10.3390/jpm10040246 Authors: Michael A. Ulm Tiffany M. Redfern Ben R. Wilson Suriyan Ponnusamy Sarah Asemota Patrick W. Blackburn Yinan Wang Adam C. ElNaggar Ramesh Narayanan Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Signif icant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

JPM, Vol. 10, Pages 245: An Overview of the Application of Systems Biology in an Understanding of Chronic Rhinosinusitis (CRS) Development

Alexandros G.Sfakianakis shared this article with you from Inoreader JPM, Vol. 10, Pages 245: An Overview of the Application of Systems Biology in an Understanding of Chronic Rhinosinusitis (CRS) Development Μέσω Journal of Personalized Medicine JPM, Vol. 10, Pages 245: An Overview of the Application of Systems Biology in an Understanding of Chronic Rhinosinusitis (CRS) Development Journal of Personalized Medicine doi: 10.3390/jpm10040245 Authors: Michał Michalik Alfred Samet Agnieszka Dmowska-Koroblewska Adrianna Podbielska-Kubera Małgorzata Waszczuk-Jankowska Wiktoria Struck-Lewicka Michał J. Markuszewski Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses. It is defined as the presence of a minimum of two out of four main symptoms such as hyposmia, facial pain, nasal blockage, and discharge, which last for 8–12 weeks. CRS significantly impairs a patient’s quality of life. It needs special treatment mainly focusing on preventing local infection/inflammation with corticosteroid sprays or improving sinus drainage using nasal saline irrigation. When other treatments fail, endoscopic sinus surgery is considered an effective option. According to the state-of-the-art knowledge of CRS, there is more evidence suggesting that it is more of an inflammatory disease than an infectious one. This condition is also treated as a multifactorial inflammatory disorder as it may be triggered by various factors, such as bacterial or fungal infections, airborne irritants, defects in innate immunity, or the presence of concomitant diseases. Due to the inc omplete understanding of the pathological processes of CRS, there is a continuous search for new indicators that are directly related to the pathogenesis of this disease—e.g., in the field of systems biology. The studies adopting systems biology search for possible factors responsible for the disease at genetic, transcriptomic, proteomic, and metabolomic levels. The analyses of the changes in the genome, transcriptome, proteome, and metabolome may reveal the dysfunctional pathways of inflammatory regulation and provide a clear insight into the pathogenesis of this disease. Therefore, in the present paper, we have summarized the state-of-the-art knowledge of the application of systems biology in the pathology and development of CRS. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

SEX DISPARITIES IN COVID-19 SEVERITY AND OUTCOME: ARE MEN WEAKER OR WOMEN STRONGER?

Alexandros G.Sfakianakis shared this article with you from Inoreader SEX DISPARITIES IN COVID-19 SEVERITY AND OUTCOME: ARE MEN WEAKER OR WOMEN STRONGER? Μέσω NEN : Last 20 articles The COVID-19 outbreak is a global public health issue, having profound effects on most aspects of societal well-being, including physical and mental health. A plethora of studies, globally, have suggested the existence of a sex disparity in the outcome of COVID-19 patients, that is mainly due to mechanisms of viral infection, immune response to the virus, development of a hyperinflammation, and development of systemic complications, particularly thromboembolism. These differences appear to be more pronounced in elderly COVID-19 patients. Epidemiological data report a sex difference in the severity and outcome of COVID-19 disease with a more favourable course of the disease in women compared to men, regardless of age range although the rate of SARS-CoV-2 infection seems to be similar in both sexes. Sex hormones, including androgens and estrogens, may not only impact viral entry and load, but also shape the clinical manifestations, complications and, ultimately, the outcome of CO VID-19 disease. The current review comprehensively summarizes current literature on sex disparities in susceptibility and outcomes of COVID-19 disease as well as the literature underpinning the pathophysiological and molecular mechanisms, which may provide a rationale to a sex disparity. These include sex hormone influences on molecules that facilitate virus entry and priming, as well as the immune and inflammatory response, as well as coagulation and thrombosis diathesis. Based on present evidence, women appear to be relatively protected from COVID-19 because of a more effective immune response and a less pronounced systemic inflammation, with consequent moderate clinical manifestations of the disease, together with a lesser predisposition to thromboembolism. Conversely, men appear to be particularly susceptible to COVID-19 disease because of a less effective immune response with consequent increased susceptibility to infections, together with a greater predisposition to thromboemb olism. In elderlies, sex disparities in overall mortality following SARS-CoV-2 infection is even more palpable, as elderly men appear more prone to severe COVID-19 because of a greater predisposition to infections, a weaker immune defence and an enhanced thrombotic state compared to women. The review highlights potential novel therapeutic approaches employing the administration of hormonal or anti-hormonal therapy in combination with antiviral drugs in COVID-19 patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Higher content of microcystin‐leucine‐arginine promotes the survival of intrahepatic cholangiocarcinoma cells via regulating SET resulting in the poorer prognosis of patients

Alexandros G.Sfakianakis shared this article with you from Inoreader Higher content of microcystin‐leucine‐arginine promotes the survival of intrahepatic cholangiocarcinoma cells via regulating SET resulting in the poorer prognosis of patients Μέσω Cell Proliferation MC‐LR was able to inhibit the activity of PP2A and activate MEK‐ERK signalling pathway via up‐regulating the expression of SET, resulting in the ICC cell proliferation and poor prognosis. Abstract Background & Aims Intrahepatic cholangiocarcinoma (ICC) has over the last 10 years become the focus of increasing concern largely due to its rising incidence and high mortality rates worldwide. Microcystin‐leucine‐arginine (MC‐LR) has been reported to be carcinogenic, but there are no data on the linkage between MC‐LR and ICC. This study aimed to explore whether the content levels of MC‐LR in the tumour tissues of ICC patients be associated with the prognosis and if so, to characterize the mechanism in ICC cells. Methods We conducted a retrospective study to evaluate the prognostic value of MC‐LR in ICC after resection. All patients were divided into two groups according to the content of MC‐LR in tumour via immunohistochemistry: low‐MC‐LR group (n = 28) and high‐MC‐LR group (n = 30). Results Multivariate analysis showed high‐MC‐LR level was the prognostic factor for OS and RFS after hepatectomy (P = .011 and .044). We demonstrated that MC‐LR could promote the survival of human ICC cell lines and SET was identified as an important mRNA in the progression via RNA array. Conclusions We provide evidence that MC‐LR was an independent prognostic factor for ICC in humans by modulating the expression of SET in human ICC cells. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Active ingredients and mechanisms of Phellinus linteus (grown on Rosa multiflora) for alleviation of Type 2 diabetes mellitus through network pharmacology

Alexandros G.Sfakianakis shared this article with you from Inoreader Active ingredients and mechanisms of <em>Phellinus linteus</em> (grown on <em>Rosa multiflora</em>) for alleviation of Type 2 diabetes mellitus through network pharmacology Μέσω Gene Publication date: Available online 26 November 2020 Source: Gene Author(s): Ki Kwang Oh, Md Adnan, Dong Ha Cho View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The homeostatic role of hydrogen peroxide, superoxide anion and nitric oxide in the vasculature

Alexandros G.Sfakianakis shared this article with you from Inoreader The homeostatic role of hydrogen peroxide, superoxide anion and nitric oxide in the vasculature Μέσω Free Radical Biology and Medicine Publication date: Available online 25 November 2020 Source: Free Radical Biology and Medicine Author(s): Tiago J. Costa, Paula Rodrigues Barros, Cristina Arce, Jeimison Duarte Santos, Júlio da Silva-Neto, Gustavo Egea, Ana Paula Dantas, Rita C. Tostes, Francesc Jimenez-Altayó View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice

Alexandros G.Sfakianakis shared this article with you from Inoreader Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice Μέσω Free Radical Biology and Medicine Publication date: Available online 26 November 2020 Source: Free Radical Biology and Medicine Author(s): Kang Han, Xiaofang Jin, Xin Guo, Guoli Cao, Siyu Tian, Yiming Song, Yuanyuan Zuo, Peng Yu, Guofen Gao, Yan-Zhong Chang View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lung cancer: Nodules and distended veins are some of the lesser-known signs of the disease

a.l.s.f.akia shared this article with you from Inoreader Lung cancer: Nodules and distended veins are some of the lesser-known signs of the disease Via MedWorm Cancer & Oncology Top 20 LUNG cancer is one of the most common and serious types of cancer, with around 47,000 people diagnosed with the condition every year in the UK. But warning signs of the disease do not always present as a new and persistent cough. Noticing nodules or distended veins could mean you're at risk. (Source: Daily Express - Health) MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Updates on the Treatment of Invasive Breast Cancer: Quo Vadimus?

a.l.s.f.akia shared this article with you from Inoreader Updates on the Treatment of Invasive Breast Cancer: Quo Vadimus? Via MedWorm Cancer & Oncology Research Malignancies of the mammary gland constitute a global health burden in women of all ages. In 2018, breast cancer held the first place regarding cancer incidence and cancer-related mortality among women worldwide, with approximately 2.1 million new cases and 600,000 deaths, respectively [1]. These cases present geographic variations which have not been fully explained [1]. More specifically, incidence measures of female breast cancer span from 26 per 100,000 females in South Central Asia to 94 per 100,000 in Australia [1], while European countries seem to share a common incidence of around 90 to 92 per 100,000 [1]. (Source: Maturitas) MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Vaccines, Vol. 8, Pages 706: DC-Based Vaccines for Cancer Immunotherapy

alkiviadis.1961 shared this article with you from Inoreader Vaccines, Vol. 8, Pages 706: DC-Based Vaccines for Cancer Immunotherapy Via Vaccines Vaccines, Vol. 8, Pages 706: DC-Based Vaccines for Cancer Immunotherapy Vaccines doi: 10.3390/vaccines8040706 Authors: Chunmei Fu Li Zhou Qing-Sheng Mi Aimin Jiang As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell r esponses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of an tigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3 ζ/TGFβR1 axis.

alwin shared this article with you from Inoreader LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3 ζ/TGFβR1 axis. Via Neoplasma In conclusion, this work exposed a novel role and regulatory mechanism of MEG8 in HCC and provided new insight into the treatment of HCC. PMID: 33147050 [PubMed - as supplied by publisher] (Source: Neoplasma) View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.