#pre-metastatic niche

[laurazukerman-blog]

Metastatic Cancer Cell Behavior and the Pre Metastatic niche

Metastatic cancel cell behavior and the pre metastatic niche are two important concepts in cancer research. Here are a few key examples and points to help you understand about each. Metastatic cancer cell behavior: Metastatic cancer cells are cells that have spread primary tumor to other parts of the body. Metastatic is a complex process that involves several steps, including the invasion of…

[tumimmtxpapers]

The pro-tumorigenic responses in metastatic niches: an immunological perspective

Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer... http://dlvr.it/SYq7BG

[selfpressexpress]

Forcing wearing masks is not only unethical, it is illegal

http://12160.info/m/blogpost?id=2649739%3ABlogPost%3A2035264

Forcing wearing masks is not only unethical, it is illegal without medical evaluation to determine the person's ability to wear a mask.

Surgical masks are not designed to protect the wearer from inhaling airborne bacteria or virus particles and are less effective than respirators, which are designed for this purpose. - Wikipedia.

 All workers who are required to wear tight-fitting respirators (e.g., N95 respirators, elastomerics) must have a medical evaluation to determine the worker’s ability to wear a respirator, and if medically cleared, a respirator fit test needs to be performed using the same model available in the workplace.

https://www.cdc.gov/niosh/topics/healthcarehsps/respiratory.html

https://www.youtube.com/watch?v=YDngH6X1MVg

References

bin-Reza F et al. The use of mask and respirators to prevent transmission of influenza: A systematic review of the scientific evidence. Resp Viruses 2012;6(4):257-67.

Zhu JH et al. Effects of long-duration wearing of N95 respirator and surgical facemask: a pilot study. J Lung Pulm Resp Res 2014:4:97-100.

Ong JJY et al. Headaches associated with personal protective equipment- A cross-sectional study among frontline healthcare workers during COVID-19. Headache 2020;60(5):864-877.

Bader A et al. Preliminary report on surgical mask induced deoxygenation during major surgery. Neurocirugia 2008;19:12-126.

Shehade H et al. Cutting edge: Hypoxia-Inducible Factor-1 negatively regulates Th1 function. J Immunol 2015;195:1372-1376.

Westendorf AM et al. Hypoxia enhances immunosuppression by inhibiting CD4+ effector T cell function and promoting Treg activity. Cell Physiol Biochem 2017;41:1271-84.

Sceneay J et al. Hypoxia-driven immunosuppression contributes to the pre-metastatic niche. Oncoimmunology 2013;2:1 e22355.

Blaylock RL. Immunoexcitatory mechanisms in glioma proliferation, invasion and occasional metastasis. Surg Neurol Inter 2013;4:15.

Aggarwal BB. Nucler factor-kappaB: The enemy within. Cancer Cell 2004;6:203-208.

Savransky V et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Resp Crit Care Med 2007;175:1290-1297.

Baig AM et al. Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 2020;11:7:995-998.

Wu Y et al. Nervous system involvement after infection with COVID-19 and other coronaviruses.

Ritter et al., in 1975, found that “the wearing of a surgical face mask had no effect upon the overall operating room environmental contamination.”

Ha’eri and Wiley, in 1980, applied human albumin microspheres to the interior of surgical masks in 20 operations. At the end of each operation, wound washings were examined under the microscope. “Particle contamination of the wound was demonstrated in all experiments.”

Laslett and Sabin, in 1989, found that caps and masks were not necessary during cardiac catheterization. “No infections were found in any patient, regardless of whether a cap or mask was used,” they wrote. Sjøl and Kelbaek came to the same conclusion in 2002.

In Tunevall’s 1991 study, a general surgical team wore no masks in half of their surgeries for two years. After 1,537 operations performed with masks, the wound infection rate was 4.7%, while after 1,551 operations performed without masks, the wound infection rate was only 3.5%.

A review by Skinner and Sutton in 2001 concluded that “The evidence for discontinuing the use of surgical face masks would appear to be stronger than the evidence available to support their continued use.”

Lahme et al., in 2001, wrote that “surgical face masks worn by patients during regional anaesthesia, did not reduce the concentration of airborne bacteria over the operation field in our study. Thus they are dispensable.”

Figueiredo et al., in 2001, reported that in five years of doing peritoneal dialysis without masks, rates of peritonitis in their unit were no different than rates in hospitals where masks were worn.

Bahli did a systematic literature review in 2009 and found that “no significant difference in the incidence of postoperative wound infection was observed between masks groups and groups operated with no masks.”

Surgeons at the Karolinska Institute in Sweden, recognizing the lack of evidence supporting the use of masks, ceased requiring them in 2010 for anesthesiologists and other non-scrubbed personnel in the operating room. “Our decision to no longer require routine surgical masks for personnel not scrubbed for surgery is a departure from common practice. But the evidence to support this practice does not exist,” wrote Dr. Eva Sellden.

Webster et al., in 2010, reported on obstetric, gynecological, general, orthopaedic, breast and urological surgeries performed on 827 patients. All non-scrubbed staff wore masks in half the surgeries, and none of the non-scrubbed staff wore masks in half the surgeries. Surgical site infections occurred in 11.5% of the Mask group, and in only 9.0% of the No Mask group.

Lipp and Edwards reviewed the surgical literature in 2014 and found “no statistically significant difference in infection rates between the masked and unmasked group in any of the trials.” Vincent and Edwards updated this review in 2016 and the conclusion was the same.

Carøe, in a 2014 review based on four studies and 6,006 patients, wrote that “none of the four studies found a difference in the number of post-operative infections whether you used a surgical mask or not.”

Salassa and Swiontkowski, in 2014, investigated the necessity of scrubs, masks and head coverings in the operating room and concluded that “there is no evidence that these measures reduce the prevalence of surgical site infection.”

Da Zhou et al., reviewing the literature in 2015, concluded that “there is a lack of substantial evidence to support claims that facemasks protect either patient or surgeon from infectious contamination.”

Brain Behavior, and Immunity, In press.

Perlman S et al. Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves. Virology 1989;170:556-560.

[cancersfakianakis1]

An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles

Publication date: 14 January 2019

Source: Cancer Cell, Volume 35, Issue 1

Author(s): Angelica Ortiz, Jun Gui, Farima Zahedi, Pengfei Yu, Christina Cho, Sabyasachi Bhattacharya, Christopher J. Carbone, Qiujing Yu, Kanstantsin V. Katlinski, Yuliya V. Katlinskaya, Simran Handa, Victor Haas, Susan W. Volk, Angela K. Brice, Kim Wals, Nicholas J. Matheson, Robin Antrobus, Sonja Ludwig, Theresa L. Whiteside, Cindy Sander

Summary

Tumor-derived extracellular vesicles (TEV) “educate” healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of downregulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy.

Graphical Abstract

http://bit.ly/2Mc6dqf

[rnomics]

The Impact of #miRNA in Colorectal #cancer Progression and Its Liver Metastases.

Related Articles The Impact of #miRNA in Colorectal #cancer Progression and Its Liver Metastases. Int J Mol Sci. 2018 Nov 22;19(12): Authors: Balacescu O, Sur D, Cainap C, Visan S, Cruceriu D, Manzat-Saplacan R, Muresan MS, Balacescu L, Lisencu C, Irimie A Abstract Colorectal #cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal #cancer management is to identify new prognostic factors that could better estimate the #evolution and treatment responses of this disease. Considering their role in #cancer development, progression and metastasis, #miRNAs have become an important class of molecules suitable for #cancer biomarkers discovery. We performed a systematic search of studies investigating the role of #miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific #microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of #miRNAs in controlling the epithelial⁻mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of #miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner. PMID: 30469518 [PubMed - in process] http://bit.ly/2DFGrbE

[linhgd9]

Cemiplimab-rwlc Market is Projected to Showcase Significant Growth up to 2027

“

The research team projects that the Cemiplimab-rwlc market size will grow from XXX in 2020 to XXX by 2027, at an estimated CAGR of XX. The base year considered for the study is 2020, and the market size is projected from 2020 to 2027.

The prime objective of this report is to help the user understand the market in terms of its definition, segmentation, market potential, influential trends, and the challenges that the market is facing with 10 major regions and 50 major countries. Deep researches and analysis were done during the preparation of the report. The readers will find this report very helpful in understanding the market in depth. The data and the information regarding the market are taken from reliable sources such as websites, annual reports of the companies, journals, and others and were checked and validated by the industry experts. The facts and data are represented in the report using diagrams, graphs, pie charts, and other pictorial representations. This enhances the visual representation and also helps in understanding the facts much better.

Sample@https://www.themarketinsights.com/request-sample/175116

By Market Players:, Sanofi

By Type, 350 mg Injection, Type II

By Application, Metastatic cutaneous squamous cell carcinoma (CSCC), Locally advanced CSCC

Brief about Cemiplimab-rwlc Market Report with TOC@ https://www.themarketinsights.com/report/cemiplimab-rwlc-market-175116

By Regions/Countries:, North America, United States, Canada, Mexico

East Asia, China, Japan, South Korea

Europe, Germany, United Kingdom, France, Italy, Russia, Spain, Netherlands, Switzerland, Poland

South Asia, India, Pakistan, Bangladesh

Southeast Asia, Indonesia, Thailand, Singapore, Malaysia, Philippines, Vietnam, Myanmar

Middle East, Turkey, Saudi Arabia, Iran, United Arab Emirates, Israel, Iraq, Qatar, Kuwait, Oman

Africa, Nigeria, South Africa, Egypt, Algeria, Morocoo

Oceania, Australia, New Zealand

South America, Brazil, Argentina, Colombia, Chile, Venezuela, Peru, Puerto Rico, Ecuador

Rest of the World, Kazakhstan

Discount @ https://www.themarketinsights.com/check-discount/175116

Points Covered in The Report, The points that are discussed within the report are the major market players that are involved in the market such as market players, raw material suppliers, equipment suppliers, end users, traders, distributors and etc., The complete profile of the companies is mentioned. And the capacity, production, price, revenue, cost, gross, gross margin, sales volume, sales revenue, consumption, growth rate, import, export, supply, future strategies, and the technological developments that they are making are also included within the report. This report analyzed 12 years data history and forecast., The growth factors of the market is discussed in detail wherein the different end users of the market are explained in detail., Data and information by market player, by region, by type, by application and etc, and custom research can be added according to specific requirements., The report contains the SWOT analysis of the market. Finally, the report contains the conclusion part where the opinions of the industrial experts are included.

Key Reasons to Purchase, To gain insightful analyses of the market and have comprehensive understanding of the global market and its commercial landscape., Assess the production processes, major issues, and solutions to mitigate the development risk., To understand the most affecting driving and restraining forces in the market and its impact in the global market., Learn about the market strategies that are being adopted by leading respective organizations., To understand the future outlook and prospects for the market., Besides the standard structure reports, we also provide custom research according to specific requirements.

The report focuses on Global, Top 10 Regions and Top 50 Countries Market Size of Cemiplimab-rwlc 2016-2021, and development forecast 2022-2027 including industries, major players/suppliers worldwide and market share by regions, with company and product introduction, position in the market including their market status and development trend by types and applications which will provide its price and profit status, and marketing status & market growth drivers and challenges, with base year as 2020.

Key Indicators Analysed, Market Players & Competitor Analysis: The report covers the key players of the industry including Company Profile, Product Specifications, Production Capacity/Sales, Revenue, Price and Gross Margin 2016-2021 & Sales by Product Types., Global and Regional Market Analysis: The report includes Global & Regional market status and outlook 2022-2027. Further the report provides break down details about each region & countries covered in the report. Identifying its production, consumption, import & export, sales volume & revenue forecast., Market Analysis by Product Type: The report covers majority Product Types in the Cemiplimab-rwlc Industry, including its product specifcations by each key player, volume, sales by Volume and Value (M USD)., Markat Analysis by Application Type: Based on the Cemiplimab-rwlc Industry and its applications, the market is further sub-segmented into several major Application of its industry. It provides you with the market size, CAGR & forecast by each industry applications., Market Trends: Market key trends which include Increased Competition and Continuous Innovations., Opportunities and Drivers: Identifying the Growing Demands and New Technology, Porters Five Force Analysis: The report will provide with the state of competition in industry depending on five basic forces: threat of new entrants, bargaining power of suppliers, bargaining power of buyers, threat of substitute products or services, and existing industry rivalry.

COVID-19 Impact, Report covers Impact of Coronavirus COVID-19: Since the COVID-19 virus outbreak in December 2019, the disease has spread to almost every country around the globe with the World Health Organization declaring it a public health emergency. The global impacts of the coronavirus disease 2019 (COVID-19) are already starting to be felt, and will significantly affect the Cemiplimab-rwlc market in 2021. The outbreak of COVID-19 has brought effects on many aspects, like flight cancellations; travel bans and quarantines; restaurants closed; all indoor/outdoor events restricted; over forty countries state of emergency declared; massive slowing of the supply chain; stock market volatility; falling business confidence, growing panic among the population, and uncertainty about future.,

Single User License Copy and other purchase options@ https://www.themarketinsights.com/Checkout/38055593

Table of Content

Chapter One: Report Overview

Chapter Two: Market Competition by Manufacturers

Chapter Three: Sales by Region

Chapter Four: North America

Chapter Five: East Asia

Chapter Six: Europe

Chapter Seven: South Asia

Chapter Eight: Southeast Asia

Chapter Nine: Middle East

Chapter Ten: Africa

Chapter Eleven: Oceania

Chapter Twelve: South America

Report Customization available as per requirements Request Customization@ https://www.themarketinsights.com/request-customization/175116

About us. The Market Insights is a sister company to SI Market research and The Market Insights is into reselling. The Market Insights is a company that is creating cutting edge, futuristic and informative reports in many different areas. Some of the most common areas where we generate reports are industry reports, country reports, company reports and everything in between. At The Market Insights, we give our clients the best reports that can be made in the market. Our reports are not only about market statistics, but they also contain a lot of information about new and niche company profiles. The companies that feature in our reports are pre-eminent. The database of the reports on market research is constantly updated by us. This database contains a broad variety of reports from the cardinal industries. Our clients have direct access online to our databases. This is done to ensure that the client is always provided with what they need. Based on these needs, we at The Market Insights also include insights from experts about the global industries, market trends as well as the products in the market. These resources that we prepare are also available on our database for our esteemed clients to use. It is our duty at The Market Insights to ensure that our clients find success in their endeavors and we do everything that we can to help make that possible.

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[bloghealthcom]

Mir-25-3p đóng gói trong exosomes có nguồn gốc ung thư thúc đẩy sự di căn bằng cách tăng tính thấm thành mạch và hình thành mạch máu Blog-Health.com

Bài viết Mir-25-3p đóng gói trong exosomes có nguồn gốc ung thư thúc đẩy sự di căn bằng cách tăng tính thấm thành mạch và hình thành mạch máu Blog-Health.com được chia sẻ bởi website Blog-Health #bloghealth #suckhoe #lamdep #sinhly

Bài viết bởi Tiến sĩ Thân Thị Trang Uyên - Chuyên viên Y tế - tế bào gốc - Viện nghiên cứu Tế bào gốc và Công nghệ gen Vinmec

<!-- -->

Exosomes có nguồn gốc từ tế bào ung thư khi đây được coi là nguyên nhân chính hình thành các ổ tiền di căn do ung thư gây ra tại vị trí không có khối u. Hiện nay cơ chế exosomes có nguồn gốc ung thư vẫn đang được nghiên cứu thêm.

1. Exosomes và mối liên hệ tế bào ung thư

Exosomes (là loại túi tiết nhỏ đóng kín, có kích thước nano mét) có nguồn gốc từ tế bào ung thư được coi là nguyên nhân chính dẫn đến sự hình thành các ổ tiền di căn do ung thư gây ra tại vị trí không có khối u, tuy nhiên cơ chế của hiện tượng này vẫn chưa được nghiên cứu kỹ. Quan trọng nhất, các exosomes lấy từ huyết thanh của bệnh nhân ung thư đã được chứng minh là dấu hiệu đáng tin cậy để chẩn đoán ung thư. Do vậy, cơ chế mà exosomes có nguồn gốc ung thư điều chỉnh sự hình thành mạch và tính thấm thành mạch cần phải được nghiên cứu thêm.

2. Ung thư đại trực tràng và exosomes

Mới đây, nghiên cứu của Zeng và cộng sự (2020) cho thấy rằng, miR-25-3p (là một miRNA thúc đẩy di căn ung thư đại trực tràng) có thể được chuyển từ tế bào ung thư đại trực tràng sang tế bào nội mô thông qua exosomes. Tiếp theo đó, miR-25-3p trong exosomes điều chỉnh sự biểu hiện của VEGFR2, ZO1, Occludin và Claudin 5 trong các tế bào nội mô bằng cách điều khiển biểu hiện của các gen đích KLF2 và KLF4. Sự hoạt động của KLF2 làm giảm đáng kể quá trình hình thành mạch trong khi KLF4 cản trở đáng kể tính thấm thành mạch. Do đó, khi miR-25-3p từ exosomes ức chế hoạt động của KLF2 và KLF4 sẽ thúc đẩy hình thành mạch và tính thấm thành mạch. Ngoài ra, trong các mô hình chuột bị ung thư, miR-25-3p trong exosomes từ các tế bào ung thư đại trực tràng còn tác động gây ra sự rò rỉ mạch máu, hình thành các ổ di căn và làm tăng khả năng di căn của tế bào ung thư đến gan và phổi.

Hơn nữa, miR-25-3p trong exosomes có thể được sử dụng như một dấu ấn sinh học để chuẩn đoán sự di căn của ung thư đại trực tràng. Mức độ biểu hiện của miR-25-3p trong exosomes tuần hoàn trong máu của bệnh nhân ung thư có di căn cao hơn đáng kể so với những bệnh nhân ung thư nhưng chưa có di căn. Trong khi đó, lượng miR-25-3p trong exosomes của bệnh nhân ung thư lại giảm đi rất đáng kể sau khi bệnh nhân được phẫu thuật loại bỏ khối u.

Hình ảnh cấu trúc của một miR-25-3p

Do vậy, xét nghiệm máu định lượng miR-25-3p trong exosomes sẽ rất hữu ích để chẩn đoán ung thư đại trực tràng và tiên lượng bệnh nhân có nguy cơ di căn cao để điều trị dự phòng.

Hiện nay Bệnh viện Đa khoa Quốc tế Vinmec là một trong những bệnh viện đảm bảo trang thiết bị hiện đại, đội ngũ bác sĩ, nhân viên giỏi, giàu kinh nghiệm với các giáo sư, bác sĩ hàng đầu trong và ngoài nước cùng hệ thống phòng bệnh, xét nghiệm tiên tiến cho phép thực hiện các kỹ thuật sàng lọc ung thư mới nhất.

Vì thế, khi có vấn đề về sức khỏe, bệnh nhân có thể liên hệ tới bệnh viện để được tư vấn và đặt lịch thăm khám trong thời gian sớm nhất.

Để được tư vấn trực tiếp, Quý Khách vui lòng bấm số HOTLINE hoặc đăng ký trực tuyến TẠI ĐÂY. Ngoài ra, Quý khách có thể Đăng ký tư vấn từ xa TẠI ĐÂY

Tài liệu tham khảo:

Zeng, Z., Li, Y., Pan, Y. et al. Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun 9, 5395 (2018). https://ift.tt/2TGi2Ne

source https://blog-health.com/mir-25-3p-dong-goi-trong-exosomes-co-nguon-goc-ung-thu-thuc-day-su-di-can-bang-cach-tang-tinh-tham-thanh-mach-va-hinh-thanh-mach-mau-blog-health-com/

[abbkine]

New Post has been published on Abbkine - Antibodies, proteins, biochemicals, assay kits for life science research

Hard work, Do not forget your initiative mind-—Abbkine Breaks 1400 citations

Since Abbkine document collection began, as of December 31, 2019, the number of English articles published by google using Abbkine products has exceeded 1400, with an impact factor exceeding 5400 points.

Thank you for your trust and support to Abbkine. We will continuously stimulate our internal creativity, provide competitive biomedical products and services, and continuously create maximum value for our customers. With a view to becoming a respected and world-class provider of biomedical products and services.

Figure 1: Number of English Articles Published Using Abbkine Products from 2017 to 2019

In December 2019, Abbkine added 200+ citations. Some high-score citations are as below.

LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

https://doi.org/10.1016/j.cell.2019.07.021

Magazine: Cell

Impact: 24.38

Abstract: Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

Products using from Abbkine:

IPKine™ HRP, Goat Anti-Mouse IgG HCS (CAT#: A25112)

IPKine™ HRP, Goat Anti-Mouse IgG LCS (CAT#: A25012)

2. EMS1 and BRI1 control separate biological processes via extracellular domain diversity and intracellular domain conservation.

https://www.nature.com/articles/s41467-019-12112-w

Magazine: Nature Communications volume

Impact: 12.19

Abstract: In flowering plants, EMS1 (Excess Microsporocytes 1) perceives TPD1 (Tapetum Determinant 1) to specify tapeta, the last somatic cell layer nurturing pollen development. However, the signaling components downstream of EMS1 are relatively unknown. Here, we use a molecular complementation approach to investigate the downstream components in EMS1 signaling. We show that the EMS1 intracellular domain is functionally interchangeable with that of the brassinosteroid receptor BRI1 (Brassinosteroid Insensitive 1). Furthermore, expressing EMS1 together with TPD1 in the BRI1 expression domain could partially rescue bri1 phenotypes, and led to the dephosphorylation of BES1, a hallmark of active BRI1 signaling. Conversely, expressing BRI1 in the EMS1 expression domain could partially rescue ems1 phenotypes. We further show that PpEMS1 and PpTPD1 from the early land plant Physcomitrella patens could completely rescue ems1 and tpd1 phenotypes, respectively. We propose that EMS1 and BRI1 have evolved distinct extracellular domains to control different biological processes but can act via a common intracellular signaling pathway.

Products using from Abbkine:

Anti-Plant Actin Mouse Monoclonal Antibody (3T3) (CAT#: A01050)

3. PLK4 deubiquitination by Spata2‐CYLD suppresses NEK7‐mediated NLRP3 inflammasome activation at the centrosome.

https://www.embopress.org/doi/abs/10.15252/embj.2019102201

Magazine: EMBO JOURNAL

Impact: 10.55

Abstract: The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase‐1 and drive the maturation of proinflammatory cytokines IL‐1β and IL‐18. NLRP3 inflammasome activity must be tightly controlled, as its over‐activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo‐like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA‐mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3‐associated inflammatory diseases.

Products using from Abbkine:

IFKine™ Green Donkey Anti-Mouse IgG (CAT#: A24211)

4. Cross-Microbial Protection via Priming a Conserved Immune Co-Receptor through Juxtamembrane Phosphorylation in Plants

https://doi.org/10.1016/j.chom.2019.10.010

Magazine: Cell Host & Microbe

Impact: 10.5

Abstract: Living organisms can be primed for potentiated responses to recurring stresses based on prior experience. However, the molecular basis of immune priming remains elusive in plants that lack adaptive immunity. Here, we report that bacterial challenges can prepare plants for fungal attacks by inducing juxtamembrane phosphorylation of CERK1, the co-receptor indispensable for signaling in response to the fungal elicitor chitin. This phosphorylation is mediated by BAK1, a co-receptor for signaling in response to multiple elicitors. BAK1 interacts with CERK1, and loss of BAK1 reduces priming phosphorylation of CERK1. Juxtamembrane phosphomimetic mutations of CERK1 confer accelerated chitin responses and fortified fungal resistance without triggering constitutive immunity, whereas juxtamembrane phosphodeficient mutations diminish bacteria-induced protection against fungal infection. These findings reveal that crosstalk between cell-surface immune co-receptors can prime defense and demonstrate that juxtamembrane phosphorylation of plant receptor-like kinases can occur independent of kinase activation to place the protein into a prime state.

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Anti-GST Tag Mouse Monoclonal Antibody (2A8) (CAT#: A02030)

5. Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts

https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-1101-4

Magazine: Molecular Cancer

Impact: 9.17

Abstract: Carcinoma-associated fibroblasts (CAFs) have been known to promote cancer progression by modifying the primary tumor microenvironment. We aimed to elucidate the intercellular communication between CAFs and secondary organs in salivary adenoid cystic carcinoma (SACC) metastasis.

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FITC, Goat Anti-Rabbit IgG (CAT#: A22120)

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Dylight 549, Goat Anti-Rabbit IgG (CAT#: A23320) Please learn more details from https://www.abbkine.com/publications/ .

[leedsomics]

Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.

Related Articles Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies. Semin Cancer Biol. 2017 Jun;44:153-169 Authors: Le Large TYS, Bijlsma MF, Kazemier G, van Laarhoven HWM, Giovannetti E, Jimenez CR Abstract Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches. PMID: 28366542 [PubMed - indexed for MEDLINE] http://dlvr.it/QLzrP5

[sisiad]

Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

http://dlvr.it/PzPdv5

[itsmedicinesfakianakis]

Cancers, Vol. 9, Pages 105: The Role of Cancer-Derived Exosomes in Tumorigenicity & Epithelial-to-Mesenchymal Transition

Cancers, Vol. 9, Pages 105: The Role of Cancer-Derived Exosomes in Tumorigenicity & Epithelial-to-Mesenchymal Transition

Cancers doi: 10.3390/cancers9080105

Authors: Robert Blackwell Kimberly Foreman Gopal Gupta

Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30–100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents. Exosomes are involved in intercellular signaling, both by membrane fusion to recipient cells with deposition of exosomal contents into the cytoplasm and by the binding of recipient cell membrane receptors. Recent work has implicated cancer-derived exosomes as an important mediator of intercellular signaling and EMT, with resultant transformation of cancer cells to a more aggressive phenotype, as well as the tropism of metastatic disease in specific cancer types with the establishment of the pre-metastatic niche.

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from OtoRhinoLaryngology - Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ur5c8g

[cancersfakianakis1]

Biomaterial scaffolds recruit an aggressive population of metastatic tumor cells in vivo

For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic pre-metastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor cells (PT), similar to cells derived from lung micrometastases (LUNG). SCAF cells were more aggressive in vitro, demonstrated higher levels of migration, invasion, and mammosphere formation, and had a greater proportion of cancer stem cells than PT. SCAF were highly enriched for gene expression signatures associated with metastasis and had associated genomic structural changes including globally enhanced entropy. Collectively, our findings demonstrate that SCAF cells are distinct from PT and more closely resemble LUNG, indicating that tumor cells retrieved from scaffolds are reflective of cells at metastatic sites. https://ift.tt/2GNsD1s

[naivelocus]

Exosomes: Key mediators of metastasis and pre-metastatic niche formation

Publication date: Source:Seminars in Cell & Developmental Biology Author(s): Richard J. Lobb, Luize G. Lima, Andreas Möller — Seminars in Cell & Developmental Biology

[cancersfakianakis1]

Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes

The lymphatic network remodeling may guide tumor metastasis in a sentinel lymph node (SLN). Although tumor‐derived exosomes have been demonstrated to modify the microenvironment in adjacent organs and initiate a pre‐metastatic niche, their influence on the lymphatic network in SLNs has not been explained. Here, we show that CT26 cell exosomes (Exo) promote the proliferation of lymphatic endothelial cells and the formation of lymphatic network in SLN, facilitating the SLN metastasis of colorectal cancer (CRC). Uptake of Exo by macrophages promoted VEGFC secretion both in vivo and in vitro. Exo increased the frequency of F4/80+ macrophages in the SLN. Macrophage ablation by clodrosome prevented the exosomal effect on lymphatic network remodeling and SLN metastasis. Exosomal IRF‐2 was highly expressed in serum exosomes isolated from CRC patients with LN metastasis relative to patients without LN metastasis and healthy controls. Mechanistically, exosomal IRF‐2 induced the release of VEGFC by macrophages. An IRF‐2 knockdown attenuated the lymphatic network remodeling in the SLN and suppressed the SLN metastasis. Our data suggest that exosomal IRF‐2 remodels the lymphatic network in an SLN and may predict the development of CRC LN metastases.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RLGuGx

[cancersfakianakis1]

P02.13 Before requiring a cure: towards preventing the outgrowth of brain metastases

Abstract

Background

Brain metastases (BM) are a devastating and frequent complication in patient with metastatic cancer. Survival is severely limited as the current treatment strategies have to conquer several obstacles in symptomatic BM including the heterogenous composition of the blood-brain barrier and the altered microenvironment characteristics. “Prevent_BM” is a collaborative effort of five research groups, both clinical and pre-clinical, to identify a treatment concept targeting the formation of early BM and preventing the outgrowth to macro-metastases. In Prevent_BM, the preclinical studies focus on tumor cell-astrocyte gap junction connections, the PI3K/mTor pathway, improving brain-tropism of T-cells and the role of the pro-metastatic perivascular niche. These targets will be validated in a clinical setting, and state-of-the-art bioinformatics platform allows integration and analysis of the results.

Material and Methods

To monitor the early steps of brain colonization in real time, we employ intravital multiphoton laser-scanning microscopy (MPLSM) through a chronic cranial window in mice. Following intracardiac injection of fluorescent tumor cells, we can study the effect of different treatments on BM growth over the period of weeks.

Results

Intravital imaging allows us to investigate the effects of PI3K/mTor inhibitors on BM growth over time, as a potential target strategy for BM prevention. While studying the role of tumor cell-astrocytes in BM formation, we observed tumor-microtube formation in a subset of tumor cells, analogue to the connections formed by glioblastoma cells. To visualize tumor cell-astrocyte connections, we can measure the transfer of gap-junction permeable dye in vivo. Here, we find that the microtube-forming metastatic cells indeed take up the SR101 dye, with similar dynamics as astrocyte cells. The intravital MPLSM approach uniquely enables studying how the tumor microenvironment and therapeutic agents affect the development of BM, and allows revealing the BM immune-surveillance and the structural organization of the blood-tumor-barrier. Importantly, the remodeling of the brain vasculature during metastatic seeding can monitored during the early steps of colonization and metastatic outgrowth. Hereto, we can correlate in vivo imaging to 3D electron microscopy to reveal the dynamic interactions between tumor cells and the neurovascular unit at high resolution.

Conclusion

Upon completion of Prevent_BM, we expect to have generated a unique database, allowing deciding how to move forward with a first-of-its-kind, randomized clinical trial to prevent the symptomatic occurrence of BM. Preventing future metastasis outgrowth with a well-tolerated, low-dose targeted systemic treatment, would fundamentally change the course of many patients suffering from metastatic cancer. https://ift.tt/2QJgmwp