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1000 results for “zoe”
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𝗞𝘆𝗹𝗲 𝗱𝗲𝗲𝗹𝘁 𝗮𝗮𝗻𝗴𝗿𝗶𝗷𝗽𝗲𝗻𝗱 𝘃𝗲𝗿𝗵𝗮𝗮𝗹 𝗶𝗻 𝗠𝗔𝗙𝗦: '𝗛𝗲𝘁 𝗹𝗲𝘃𝗲𝗻 𝗶𝘀 𝗸𝗼𝗿𝘁 𝗲𝗻 𝘃𝗹𝘂𝗰𝗵𝘁𝗶𝗴'
De zoektocht naar liefde in 'Married at First Sight' is voor Kyle (32) allesbehalve oppervlakkig. In het programma deelt hij een ingrijpend verhaal, waardoor hij de afgelopen jaren flink aan zichzelf heeft gewerkt en zijn leven compleet heeft omgegooid.
https://www.rtl.nl/boulevard/artikel/5592620/kyle-deelt-aangrijpend-verhaal-mafs
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𝗞𝘆𝗹𝗲 𝗱𝗲𝗲𝗹𝘁 𝗮𝗮𝗻𝗴𝗿𝗶𝗷𝗽𝗲𝗻𝗱 𝘃𝗲𝗿𝗵𝗮𝗮𝗹 𝗶𝗻 𝗠𝗔𝗙𝗦: '𝗛𝗲𝘁 𝗹𝗲𝘃𝗲𝗻 𝗶𝘀 𝗸𝗼𝗿𝘁 𝗲𝗻 𝘃𝗹𝘂𝗰𝗵𝘁𝗶𝗴'
De zoektocht naar liefde in 'Married at First Sight' is voor Kyle (32) allesbehalve oppervlakkig. In het programma deelt hij een ingrijpend verhaal, waardoor hij de afgelopen jaren flink aan zichzelf heeft gewerkt en zijn leven compleet heeft omgegooid.
https://www.rtl.nl/boulevard/artikel/5592620/kyle-deelt-aangrijpend-verhaal-mafs
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FYI: Jessamy Shay is hosting a #handsewing for #mending workshop at Somerville Public Library on 9/25. https://somervillepubliclibrary.assabetinteractive.com/calendar/handsewing-for-mending-workshop-with-jessamy-shay-3/
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Vacature Alert! Kom jij ons team versterken? De NMU is op zoek naar een Communicatiemedewerker en een Junior.
https://www.nmu.nl/over-ons/vacatures/
#nmu #vacature #job #duurzamevacature #communicatie #natuur #milieu #utrecht
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https://www.zeit.de/digital/internet/2025-04/techkonzerne-usa-donald-trump-zoelle-gerichtsverfahren-meta-google-apple #Techkonzerne in den #USA:
Das hatte sich #Google anders vorgestellt
Die Techkonzerne haben Donald #Trump aus gutem Grund umgarnt: Sie stecken in juristischen Problemen. Aber davor bewahrt er sie nicht. Nun beginnt ein #Prozess gegen Google. -
🤑🤑🤑 3,2 milliards d'euros ! Nouveau dividende record pour Bernard Arnault et sa famille grâce à #LVMH
Découvrez la nouvelle vidéo de Zoé Pinet 📱
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"Christlicher Fundamentalismus
& Soziale ArbeitHandreichung über Vorgehensweisen, Strategien und Netzwerke
christlich-fundamentalistischer Akteurskonstellationen in der Sozialen Arbeit"von Zoe Luginsland, Matthias Pöhl, Ruby Rebelde, Recherchekollektiv FundiWatch
Die 73seitige Broschüre kann hier als PDF gratis heruntergeladen werden:
https://fundiwatch.org/wp-content/uploads/2025/07/Christl_Fundamentalismus_Soziale_Arbeit_06-25.pdfFragen bitte nicht an mich, ich teile das nur.
#ChristlicherFundamentalismus #SozialeArbeit
#Fundamentalismus -
A12 blokkade tijdens de NAVO-top
A12, Den Haag, woensdag 25 juni om 12:00 CEST
(English below)
Tijdens de NAVO-top, op woensdag 25 juni om 12.00 uur, blokkeren Extinction Rebellion en Extinction Rebellion Justice Now de A12 in Den Haag. Vanwege de NAVO-top gaat het dit keer om een A12-blokkade met eisen die daar betrekking op hebben: stop de genocide, stop racisme en facisme, stop klimaatontwrichting.
Woordvoerder Rozemarijn van ’t Einde: “Terwijl regeringsleiders steeds grotere wapenbudgetten binnenslepen, pleegt Israël genocide op de Palestijnen, zitten we opgescheept met racistisch en fascistisch beleid en woekert de klimaatcrisis voort. De NAVO-top is het uitgelezen moment om grote veranderingen te eisen. Daarom demonstreren wij op de A12, ‘within sight and sound’ van de Tweede Kamer en de VNO-NCW, die sterk voor defensie lobbyt. Nederland moet rechtvaardige keuzes maken.”
De eisen van de A12-blokkade
De eisen van Extinction Rebellion en Extinction Rebellion Justice Now zijn drievoudig:
Stop de genocide die Israël op de Palestijnen pleegt. In lijn met het genocideverdrag[1,2] eisen Extinction Rebellion en Extinction Rebellion Justice Now een direct einde aan alle wapenleveranties aan Israël en de instelling van harde sancties.
Stop fascisme en racisme. Stop dit extreemrechtse beleid. Stop de verspreiding van desinformatie door politici.
Stop de fossiele vernietiging. Maak per direct een einde aan fossiele subsidies en fossiele financiering, en verbied nieuwe fossiele projecten.
Stop de genocide van Israël op de Palestijnen
Het Internationaal Gerechtshof heeft vastgesteld dat het plausibel is dat Israël genocide pleegt op de Palestijnen[3] en het Internationaal Strafhof heeft arrestatiebevelen uitgevaardigd voor o.a. premier Netanyahu.[4] VN-rapporteur Francesca Albanese sprak van genocide, net als Human Rights Watch en Amnesty International, die laatste organisatie stelde op 5 december 2024 vast dat Israël genocide pleegt in Gaza.[5] Ook het NIOD spreekt van genocidaal geweld.[6] Toch is de Nederlandse regering actief betrokken bij de bewapening van Israël[7], in plaats van Israël scherp te veroordelen en sancties in te stellen.
Woordvoerder Rozemarijn van ’t Einde: “De verschrikkingen die Israël tegen de Palestijnen begaat zijn nauwelijks te bevatten. Nog onbegrijpelijker is de onwil om in te grijpen. Hoe kan het dat de hele wereld toekijkt terwijl er genocide wordt gepleegd? De Nederlandse regering moet nu doen wat nodig is en sancties instellen. Stop de genocide!”
Stop fascisme en racisme
Na een lange reeks (centrum)rechtse kabinetten gaat Nederland sinds 2023 gebukt onder extreemrechts beleid. Veel Nederlanders zijn ontevreden. Niet gek, want Nederland is geen rechtvaardig land. Of het nu over welvaart, woningen, onderwijs, zorg of openbaar vervoer gaat: in Nederland is alles oneerlijk verdeeld. Racisme en discriminatie vieren hoogtij[8]. Mensen van kleur hebben dagelijks te maken met racistische structuren in de samenleving: ze vinden minder makkelijk een stageplaats[9], een huis[10] of een baan.[11] Ondanks veelvuldige ontkenning door de politie vindt etnische profilering nog steeds regelmatig plaats.[12]
Woordvoerder Rozemarijn van ’t Einde: “Regeringspartijen en politici zoals Geert Wilders spelen in op de, veelal door henzelf veroorzaakte problemen. In plaats van het benoemen van de echte problemen proberen ze van hun verantwoordelijkheden weg te lopen door racistische sprookjes te verspreiden. Alles zou de schuld zijn van ‘asielzoekers’ en ‘migranten’. Een racistisch en fascistisch standpunt dat riekt naar de jaren dertig en veertig van de vorige eeuw. Deze hetze moet stoppen, net als de samenwerking met Wilders.”Stop fossiele vernietiging
De klimaat- en ecologische crisis is een massamoord in slow-motion, waarbij overheden en bedrijven in het Mondiale Noorden een ramp veroorzaken in het Mondiale Zuiden. Vele duizenden mensen zijn al omgekomen door hitte, droogte, hongersnoden, orkanen, bosbranden en andere klimaatrampen. Vele miljoenen of zelfs miljarden zullen volgen. De Nederlandse regering en grote bedrijven dragen dagelijks bij aan de voltrekking van deze massamoord. Door jaarlijks miljarden fossiele subsidies te verstrekken aan grootvervuilers, door de fossiele industrie met miljarden te financieren en door nieuwe fossiele projecten te starten, terwijl we de oude zouden moeten ontmantelen.
Woordvoerder Rozemarijn van ’t Einde: “De verhitting van de aarde is de grootste bedreiging voor de mensheid en dat de klimaat- en ecologische crisis tot meer gewapende conflicten leidt is bekend.[13] Toch kiezen de regering en grote bedrijven voor hun eigen korte termijn belangen: die van het grootkapitaal. Dit misdadige beleid moet nu stoppen. Stop fossiele subsidies, stop fossiele financiering, verbied nieuwe fossiele projecten.”
Wat is Extinction Rebellion Justice Now?
XR Justice Now! komt in actie voor klimaatrechtvaardigheid, en verzet zich specifiek tegen alle vormen van kolonialisme en imperialisme en alle symptomen hiervan. Iedereen heeft het recht op veiligheid, gezondheid, gemeenschap en respect. Deze rechten zijn essentieel voor een wereldwijde, rechtvaardige klimaattransitie. Voor veel mensen is klimaatmitigatie en -adaptatie niet mogelijk door aanhoudende onrechtvaardigheden in hun leven. Wereldwijde klimaatactie is niet mogelijk als deze vormen van onrecht niet worden aangekaart.
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During the NATO summit, on Wednesday, June 25 at noon, Extinction Rebellion and Extinction Rebellion Justice Now are blocking the A12 highway in The Hague. Because of the NATO summit, this time it is an A12 blockade with demands related to it: stop the genocide, stop racism and fascism, stop climate disruption.
Spokesperson Rozemarijn van ’t Einde:”While government leaders are raking in larger and larger arms budgets, Israel is committing genocide against the Palestinians, we are saddled with racist and fascist policies, and the climate crisis continues. The NATO summit is the perfect time to demand big changes. Therefore we protest on the A12 ‘within sight and sound’ of the House of Representatives and the VNO-NCW, which is lobbying strongly for the defense industry. The Netherlands must make just choices.”
The Demands of the A12 Blockade
The demands of Extinction Rebellion and Extinction Rebellion Justice Now are threefold:
Stop the genocide that Israel is committing on the Palestinians. In line with the Genocide convention [1,2], Extinction Rebellion and Extinction Rebellion Justice Now demand an immediate end to all arms deliveries to Israel and the imposition of strong sanctions.
Stop fascism and racism. Stop this right-wing extremist policy. Stop the spreading of disinformation by politicians.
Stop the fossil destruction. Immediately end fossil subsidies and fossil funding, and ban new fossil projects.
Stop Israel’s Genocide of Palestinians
The International Court of Justice has determined that it is plausible that Israel is committing genocide against the Palestinians[3], and the International Criminal Court has issued arrest warrants for Prime Minister Netanyahu, among others. [4] UN special rapporteur Francesca Albanese spoke of genocide, as did Human Rights Watch and Amnesty International, the latter organisation determined on December 5, 2024 that Israel is committing genocide in Gaza.[5] The NIOD, Institute for War, Holocaust and Genocide Studies, also speaks of genocidal violence.[6] Yet the Dutch government is still actively involved in arming Israel,[7] rather than strongly condemning Israel and imposing sanctions.Spokesperson Rozemarijn van ’t Einde: “The horrors Israel commits against the Palestinians are barely comprehensible. Even more incomprehensible is the unwillingness to intervene. How is it possible that the whole world is standing by, watching while a genocide is being committed? The Dutch government must immediately do what is necessary and impose sanctions. Stop the genocide!”
Stop Fascism and Racism
After a long series of (center-)right coalitions, the Netherlands has been suffering far-right policies since 2023. Many Dutch people are dissatisfied. Not surprising, because the Netherlands is not a fair country. Whether it is about prosperity, housing, education, healthcare or public transportation: In the Netherlands everything is unfairly distributed. Racism and discrimination are peaking [8]. People of colour have to deal with racist structures in society on a daily basis: they are less likely to find an internship [9], a house [10], or a job[11]. Despite frequent denial by police, ethnic profiling still takes place regularly. [12]
Spokesperson Rozemarijn van ’t Einde: “governing parties and politicians like Geert Wilders play on the, mostly self-inflicted, problems. Instead of naming the real problems, they try to run away from their responsibilities by spreading racist lies. Supposedly everything is the fault of ‘asylum seekers’ and ‘migrants’. A racist and fascist position that reeks of the 1930s and 1940s. This smear campaign must stop, as must its collaboration with Wilders.”
Stop Fossil Destruction
The climate- and ecological crisis is mass murder in slow-motion, with governments and corporations in the Global North causing disaster in the Global South. Many thousands have already died from heat, drought, famines, hurricanes, wild fires and other climate disasters. Many millions or even billions will follow. The Dutch government and big companies contribute on a daily basis to the unfolding of this mass murder. By providing billions of fossil subsidies to big polluters every year, by financing the fossil industry with billions and by starting new fossil projects when we should be dismantling the old ones.Spokesperson Rozemarijn van ’t Einde: “Global warming is the biggest threat to humanity, and that the climate- and ecological crisis is leading to more armed conflicts is well known [13]. Yet the government and big companies choose their own short-term interests: those of the big capital. These criminal policies must stop now. Stop fossil subsidies, stop fossil financing, ban new fossil projects.”
What is Extinction Rebellion Justice Now?
XR Justice Now! takes action for climate justice, specifically opposing all forms of colonialism and imperialism and all of its symptoms. Everyone has the right to safety, health, community and respect. These rights are essential for a global just climate transition. For many people, climate mitigation and -adaptation is impossible due to persistent injustices in their lives. Global climate action is not possible if these injustices are not addressed.
Bronnen/Sources
[1] https://www.rechtspraak.nl/Organisatie-en-contact/Organisatie/Gerechtshoven/Gerechtshof-Den-Haag/Nieuws/Paginas/Nederland-moet-de-uitvoer-van-F-35-onderdelen-naar-Israel-stoppen.aspx
[2] https://paxvoorvrede.nl/nieuws/sluit-nederland-ondanks-genocide-een-militair-verdrag-met-israel/
[3] https://www.icj-cij.org/case/192/orders
[4] https://www.icc-cpi.int/news/statement-icc-prosecutor-karim-aa-khan-kc-applications-arrest-warrants-situation-state
[5] https://www.amnesty.org/en/latest/news/2024/12/amnesty-international-concludes-israel-is-committing-genocide-against-palestinians-in-gaza/
[6] https://www.nrc.nl/nieuws/2025/05/07/in-gaza-is-sprake-van-genocidaal-geweld-zegt-de-directeur-van-het-niod-a4892423
[7] https://dimse.info/netherlands/
[8] https://www.cbs.nl/nl-nl/longread/rapportages/2024/ervaren-discriminatie-in-nederland?onepage=true
[9] https://www.gld.nl/nieuws/8118514/gediscrimineerd-tijdens-je-stage-slecht-voor-je-zelfvertrouwen
[10] https://eenvandaag.avrotros.nl/artikelen/makelaars-en-gemeenten-zoeken-naar-oplossingen-tegen-discriminatie-op-de-woningmarkt-151841
[11] https://www.uva.nl/shared-content/faculteiten/nl/faculteit-der-maatschappij-en-gedragswetenschappen/nieuws/2023/04/discriminatie-op-de-arbeidsmarkt-neemt-alleen-maar-toe.html?cb
[12] https://www.amnesty.nl/wat-we-doen/landen/mensenrechten-nederland/etnisch-profileren-door-de-politie
[13] https://unfccc.int/news/conflict-and-climatehttps://acties.todon.nl/event/a12-blokkade-tijdens-de-navo-top
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Channing Tatum posts cryptic poem after ex Zoë Kravitz gets engaged to Harry Styles
Channing Tatum has posted a cryptic poem to social media following the news that his ex-fiancée, Zoë Kravitz,…
#NewsBeep #News #Celebrities #CA #Canada #celebrityengagements #celebrityexes #CelebrityNews #ChanningTatum #Entertainment #HarryStyles #ZoeKravitz
https://www.newsbeep.com/ca/632883/ -
📰 Peter R. de Vries Foundation reageert namens familie vermiste Tanja Groen op besluit OM
https://nieuwsjunkies.nl/artikel/1EVS
🕑 14:01 | RTL Nieuws
🔸 #Zoekactie #Vermist #OM #Onderzoek #Dochter -
📰 Peter R. de Vries Foundation reageert namens familie vermiste Tanja Groen op besluit OM
https://nieuwsjunkies.nl/artikel/1EVS
🕑 14:01 | RTL Nieuws
🔸 #Zoekactie #Vermist #OM #Onderzoek #Dochter -
📰 Peter R. de Vries Foundation reageert namens familie vermiste Tanja Groen op besluit OM
https://nieuwsjunkies.nl/artikel/1EVS
🕑 14:01 | RTL Nieuws
🔸 #Zoekactie #Vermist #OM #Onderzoek #Dochter -
"Altijd op zoek naar een navelstreng
nu de eerste niet langer bestaat,
balanceer ik op de ragdunne draad
van blik tot blik, tot het ogenblik
dat ik opnieuw jij
en jij ik."HAGAR PEETERS #botd #12mei #1972 #gefeliciteerd!
Uit het #gedicht 'Koorddansen',
zie: https://collecties.kb.nl/themas/nederlandse-poezie/moderne-nederlandse-dichters/hagar-peeters/de-gedichten-van-hagar-peeters @kbnationalebibliotheek #poëzie #gedichten -
"Altijd op zoek naar een navelstreng
nu de eerste niet langer bestaat,
balanceer ik op de ragdunne draad
van blik tot blik, tot het ogenblik
dat ik opnieuw jij
en jij ik."HAGAR PEETERS #botd #12mei #1972 #gefeliciteerd!
Uit het #gedicht 'Koorddansen',
zie: https://collecties.kb.nl/themas/nederlandse-poezie/moderne-nederlandse-dichters/hagar-peeters/de-gedichten-van-hagar-peeters @kbnationalebibliotheek #poëzie #gedichten -
Hartjes Tellertje: Klop, Klop, Hoe Laat is het?
Klop, Klop, Hoe Laat is het? ⏰
Hallo daar, jonge ontdekkingsreizigers! 👋 Ik ben Mauw, jullie nieuwsgierige gids. Vandaag gaan we op zoek naar dat mysterieuze kloppen van ons hart. Ja, dat k...
🌞 Leer verder: https://leeralles.nl/hartjes-tellertje-klop-klop-hoe-laat-is-het/?feed_id=17231
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Turkse ingemaakte groente in zoet zuur.
Bekijk hoe je dit kan maken op onze blog.
#eten #food #turkse #gerechten #recepten #volg #volgers #followme #followers -
Hallo nieuwe volgers (en in het bijzonder @arthurjapin): leuk jullie hier te zien. Bijt even door. Het is echt prima toeven hier op #Mastodon.
Zeker als je je aan wat #tips houdt:
1] plaats een bericht (#toot), bijvoorbeeld even een korte #bio of een leuk nieuwtje
2] #volg veel mensen
3] #boost berichten van anderen
4] zoek even op hoe Mastodon werkt. Gebruik vooral #boosts en minder #likes
5] betaal wat euro's aan de server waar je op zit.Grootste tip: vergeet Tw
https://www.frankwatching.com/archive/2022/11/09/mastodon-server-account/
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#Atomkraft ist ein schlechtes Geschäft: "Die Europäische Investitionsbank (#EIB) versetzte der #Atomindustrie auf dem Internationalen Atomenergiegipfel in #Brüssel letzte Woche einen schweren Schlag. Sie zauderte bei der Forderung der Branche nach mehr Finanzmitteln für Atomprojekte." Unsere Zukunft ist #Erneuerbar!
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𝗡𝗶𝗲𝘂𝘄𝗲 𝘇𝗼𝗲𝗸𝘁𝗼𝗰𝗵𝘁 𝗻𝗮𝗮𝗿 𝗕𝗿𝗶𝘁𝘀𝗲 𝗠𝗮𝗱𝗲𝗹𝗲𝗶𝗻𝗲 𝗠𝗰𝗖𝗮𝗻𝗻 𝗮𝗳𝗴𝗲𝗿𝗼𝗻𝗱, 𝗿𝗲𝘀𝘂𝗹𝘁𝗮𝘁𝗲𝗻 𝗼𝗻𝗯𝗲𝗸𝗲𝗻𝗱
De nieuwe zoektocht naar sporen van de in 2007 in het zuiden van Portugal verdwenen 3-jarige Britse Maddie is na drie dagen beëindigd meldt de Portugese politie. Over resultaten van het onderzoek is niets meegedeeld.
https://www.rtl.nl/nieuws/buitenland/artikel/5512539/madeleine-maddy-mccann
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Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk JaegerTargeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases
#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.
the microenvironment of #liver metastases of #colorectal cancer (#CRC).
the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.
the effects of CCR5 blockade on the #tissue level.
Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.
The microenvironment of the invasive margin of #liver metastases.
There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.
#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).
The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.
A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.
CCR5 blockade, is a type of #therapy used to treat #cancer.
The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.
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Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk JaegerTargeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases
#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.
the microenvironment of #liver metastases of #colorectal cancer (#CRC).
the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.
the effects of CCR5 blockade on the #tissue level.
Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.
The microenvironment of the invasive margin of #liver metastases.
There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.
#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).
The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.
A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.
CCR5 blockade, is a type of #therapy used to treat #cancer.
The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.
-
Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk JaegerTargeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases
#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.
the microenvironment of #liver metastases of #colorectal cancer (#CRC).
the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.
the effects of CCR5 blockade on the #tissue level.
Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.
The microenvironment of the invasive margin of #liver metastases.
There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.
#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).
The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.
A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.
CCR5 blockade, is a type of #therapy used to treat #cancer.
The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.
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𝗢𝘂𝗱-𝗶𝗻𝘁𝗲𝗿𝗻𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗩𝗮𝗻 𝗚𝗶𝗻𝗸𝗲𝗹 (33) 𝗯𝗲ë𝗶𝗻𝗱𝗶𝗴𝘁 𝘃𝗼𝗲𝘁𝗯𝗮𝗹𝗰𝗮𝗿𝗿𝗶è𝗿𝗲
Marco van Ginkel heeft zijn voetbalcarrière beëindigd. De 33-jarige middenvelder speelde in mei zijn laatste wedstrijd voor het Portugese Boavista en gaat niet meer op zoek naar een nieuwe club. "Het was een reis vol hoogte- en dieptepunten, goede lessen en herinneringen die ik voor altijd koester",...
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𝗢𝘂𝗱-𝗶𝗻𝘁𝗲𝗿𝗻𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗩𝗮𝗻 𝗚𝗶𝗻𝗸𝗲𝗹 (33) 𝗯𝗲ë𝗶𝗻𝗱𝗶𝗴𝘁 𝘃𝗼𝗲𝘁𝗯𝗮𝗹𝗰𝗮𝗿𝗿𝗶è𝗿𝗲
Marco van Ginkel heeft zijn voetbalcarrière beëindigd. De 33-jarige middenvelder speelde in mei zijn laatste wedstrijd voor het Portugese Boavista en gaat niet meer op zoek naar een nieuwe club. "Het was een reis vol hoogte- en dieptepunten, goede lessen en herinneringen die ik voor altijd koester",...
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𝗢𝘂𝗱-𝗶𝗻𝘁𝗲𝗿𝗻𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗩𝗮𝗻 𝗚𝗶𝗻𝗸𝗲𝗹 (33) 𝗯𝗲ë𝗶𝗻𝗱𝗶𝗴𝘁 𝘃𝗼𝗲𝘁𝗯𝗮𝗹𝗰𝗮𝗿𝗿𝗶è𝗿𝗲
Marco van Ginkel heeft zijn voetbalcarrière beëindigd. De 33-jarige middenvelder speelde in mei zijn laatste wedstrijd voor het Portugese Boavista en gaat niet meer op zoek naar een nieuwe club. "Het was een reis vol hoogte- en dieptepunten, goede lessen en herinneringen die ik voor altijd koester",...
