Cancer

Eliminan tumores y sus metástasis inyectándoles fragmentos de ADN con anticuerpos anti-OX40 Número 214 – Abril 2018Cambiar tamaño: AA+A++Tiempo de lectura: 11 minutos Un equipo de investigadores de la Universidad de Stanford supervisado por Ronald Levy y coordinado por Idit Sagiv-Barfi ha logrado eliminar en ratones melanomas, linfomas -neoplasias en sangre, médula ósea y/o ganglios linfáticos- y tumores de mama y colon inyectando directamente en ellos un pequeño fragmento de ADN y anticuerpos anti-OX40 logrando así que los linfocitos destruyeran tanto los tumores primarios como las metástasis distantes localizadas en otros órganos. Lográndose el éxito al primer intento en 87 de 90 casos y al segundo en los 3 restantes. El trabajo ha sido publicado en Science Translational Medicine. El resultado es tan extraordinario que ahora quieren realizar un ensayo clínico con 15 pacientes con linfomas; es más, se plantean la posibilidad de diseñar tratamientos que bloqueen de manera específica el posible crecimiento de los tumores que surgen por mutaciones genéticas como es el caso de los genes BRCA 1 y 2 en el cáncer de mama. https://www.dsalud.com/reportaje/eliminan-tumores-metastasis-inyectandoles-fragmentos-adn-anticuerpos-anti-ox40/

Una «vacuna» para el cáncer En ratones, la inyección de dos moléculas directamente en tumores sólidos estimula los linfocitos T. Una vez activadas, estas células inmunitarias no solo eliminan los nódulos cancerosos, sino que también actuan sobre las metástasis distantes no tratadas. Marta Pulido Salgado La inyección conjunta de oligonucleótidos CpG y anticuerpos potenciadores de OX40 en tumores sólidos activa los linfocitos CD4+ circundantes. Éstos, además de eliminar las células cancerosas locales, también reconocen y combaten metástasis distantes. En la imagen, carcinoma de células escamosas de la cavidad oral (blanco) atacado por dos linfocitos T CD8+ citotóxicos (rojo). [Flickr/NIH] Ahora, Ronald Levy y sus colaboradores de la Universidad de Stanford, en California, han descrito un nuevo avance para este tipo de estrategia terapéutica, conocida como inmunoterapia. Según sus resultados, la administración simultánea de dos compuestos dentro de un tumor no solo lo erradica, sino que también reduce las metástasis localizadas en otros lugares del organismo. El trabajo, realizado en ratones, se ha publicado en la revista Science Translational Medicine. https://www.investigacionyciencia.es/noticias/una-vacuna-para-el-cncer-16084

BACK TO VOL. 10, NO. 426RESEARCH ARTICLECANCERShare on

Eradication of spontaneous malignancy by local immunotherapy

IDIT SAGIV-BARFIHTTPS://ORCID.ORG/0000-0002-8372-9096DEBRA K. CZERWINSKI[…]RONALD LEVYHTTPS://ORCID.ORG/0000-0003-2061-0650 +5 authors Authors Info & AffiliationsSCIENCE TRANSLATIONAL MEDICINE • 31 Jan 2018 • Vol 10, Issue 426 • DOI: 10.1126/scitranslmed.aan4488

Deliver locally, act globally

Mobilizing endogenous T cells to fight tumors is the goal of many immunotherapies. Sagiv-Barfi et al. investigated a combination therapy in multiple types of mouse cancer models that could provide sustainable antitumor immunity. Specifically, they combined intratumoral delivery of a TLR9 ligand with OX40 activation to ramp up T cell responses. This dual immunotherapy led to shrinkage of distant tumors and long-term survival of the animals, even in a stringent spontaneous tumor model. Both of these stimuli are in clinical trials as single agents and could likely be combined at great benefit for cancer patients.

It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand—and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4⁺ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers. https://www.science.org/doi/10.1126/scitranslmed.aan4488

REVIEW OX40 ligation enhances primary and memory cytotoxic T lymphocyte responses in an immunotherapy for hepatic colon metastases Ping-Ying Pan et al. Mol Ther. 2002 Oct. https://pubmed.ncbi.nlm.nih.gov/12377195/ Previously, we showed that the eradication of murine hepatic metastatic colon carcinomas was achieved by using a combination therapy with adenovirus-mediated gene delivery of interleukin 12 (IL-12) and anti-4-1BB agonistic antibody. However, the therapeutic efficacy was compromised severely when mice with tumors larger than 8 x 8 mm(2) were treated. In this report, we studied the effect of OX40 costimulation through agonistic anti-OX40 in combination with the IL-12 + anti-4-1BB immunotherapy on primary and memory anti-tumor cytotoxic T lymphocyte responses in a large-tumor setting (8 x 8 to 12 x 12 mm(2)). Tumor-infiltrating leukocytes (TILs) isolated from mice treated with the combination therapy of IL-12, anti-4-1BB, and anti-OX40 showed a significantly higher ex vivo direct cytotoxic T lymphocyte (CTL) activity against parental tumors, as compared with those from mice treated with IL-12 and anti-4-1BB. In vivo depletion of CD4(+)T cells during combination therapy significantly decreased the number of tumor-infiltrating CD8(+)T cells and their cytotoxic activity in mice treated with IL-12 + anti-4-1BB + anti-OX40 combination therapy but not in the group treated with IL-12 + anti-4-1BB, which indicated that in vivo OX40 engagement on CD4(+) T cells led to the higher CTL responses observed in animals treated with IL-12 + anti-4-BB + anti-OX40 combination therapy. Furthermore, the combination therapy of IL-12, anti-4-1BB, and anti-OX40 resulted in a significantly higher survival rate in treated mice, as compared with treatment with IL-12 and anti-4-1BB. More importantly, long-term surviving mice from the combination therapy with IL-12, anti-4-1BB, and anti-OX40 exhibited higher memory CTL responses against parental tumor cells. The results demonstrated that OX40 ligation of CD4(+) T cells facilitated the development of primary and memory CTL responses against tumorcells and that coordinated immune activation by IL-12, anti-4-1BB, and anti-OX40 resulted in a significantly higher survival rate in mice with large tumor burdens. Thus, the combination therapy with the adenovirus encoding IL-12 (Adv.mIL-12) + anti-4-1BB + anti-OX40 antibodies may provide a better treatment modality for patients with advanced cancers, often associated with a state of immune suppression or tolerance.

Acta Pharmaceutica Sinica B Volume 10, Issue 3, March 2020, Pages 414-433

REVIEWTherapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity

Author links open overlay panelYuFu^abLingZhang^aShow moreOutlineShareCitehttps://doi.org/10.1016/j.apsb.2019.08.010Get rights and contentUnder a Creative Commons licenseopen access Abstract The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40–OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40–OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8⁺ T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40–OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40–OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40–OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies. https://www.sciencedirect.com/science/article/pii/S2211383519306161

REVIEW https://www.nature.com/articles/s41467-021-21383-1

Los objetos giratorios tienen inestabilidades extrañas conocidas como el efecto Dzhanibekov o el teorema de la raqueta de tenis

OE24.AT WELT| 11. DEZEMBER 2021 | 09:34 UHR PERSONALMANGEL

Italien: Ungeimpfte Ärzte sollen zurückkehren

Italien schlägt wegen fehlenden Gesundheitspersonals Alarm. Nun sollen ungeimpfte Ärzte zurückgeholt werden. Die vierte Coronavirus-Welle belastet Italien und setzt die Krankenhäuser unter Druck. Viele Gesundheitseinrichtungen sind durch den Personalmangel schwer belastet. Wegen der seit März geltenden Impfpflicht für Sanitäter wurden in den vergangenen Monaten mehrere Krankenpfleger und Ärzte in Italien suspendiert. Angesichts des starken Personalmangels, der sich über die Weihnachtsfeiertage zu verschärfen droht, wächst die Forderung nach einer Rückkehr ungeimpfter Sanitäter auf den Arbeitsplatz mit einer einfachen Form der Kontrolle: Tests alle 24 bzw. 48 Stunden. Dies ist der Vorschlag des Chefs der Vereinigung der Krankenhausleiter (ANPO), Giampiero Avrucio, Leiter der Angiologie-Abteilung am Krankenhaus von Padua. https://www.oe24.at/welt/italien-ungeimpfte-aerzte-sollen-zurueckkehren/502802049

Österreich (literally Austria) is a national Austrian daily newspaper, based in Vienna.^[1][2][3]

Österreich, a German language newspaper, was first published in Vienna by Helmut and Wolfgang Fellner on 1 September 2006.^[4][5][6] Wolfgang Fellner, the owner, publisher and editor of the daily,^[7] also launched other Austrian publications, including NEWS magazine.^[8][9] Mediengruppe Österreich GmbH is the owner of the daily.^[10]

1.  “Austria Newspapers – Austria Newspaper & News Media Guide”. Abyznewslinks. Retrieved 4 November 2011.
2. ^ “‘Best driver’ Alonso to win – Lauda”. BBC News. 4 October 2010. Retrieved 4 November 2011.
3. ^ Bonnie Malkin (1 May 2008). “Austria: Josef Fritzl refuses to cooperate with police”. The Telegraph. Retrieved 4 November 2011.
4. ^ ^a b c Paul Krauskopf (1 October 2006). “The New Österreich”. The Vienna Review. Retrieved 6 October 2013.
5. ^ Martina Thiele. “Press freedom and pluralism in Europe” (PDF). Intellect Books. Retrieved 6 October 2013.
6. ^ José A. García Avilés; Klaus Meier; Andy Kaltenbrunner; Miguel Carvajal; Daniela Kraus (2009). “Newsroom integration in Austria, Spain and Germany”. Journalism Practice. 3 (3): 285–303. doi:10.1080/17512780902798638.
7. ^ Paula Sutter Fichtner (11 June 2009). Historical Dictionary of Austria. Scarecrow Press. p. 97. ISBN 978-0-8108-6310-1.
8. ^ “Case study: Österreich, Austria” (PDF). Tolerans. Retrieved 6 October 2013.
9. ^ Jess Smee (13 October 2008). “Haider was driving at twice speed limit”. The Guardian. Berlin. Retrieved 6 October 2013.
10. ^ ^a b Christian Fuchs (28 February 2011). Foundations of Critical Media and Information Studies. Taylor & Francis. p. 4. ISBN 978-1-136-82531-6.

The 2006 circulation of Österreich was 159,306 copies.^[14] In the period of 2007-2008 the daily had the readership of 9.34%.^[10] Its circulation for the first half of 2007 was 120,510 copies whereas for the same period in 2008 it was 129,680 copies.^[15] In 2010, the paper had a circulation of 410,000 copies.^[16]

On 16 August 2016 Österreich told the press that they would start a 24h-News-Television-Channel, in cooperation with CNN, on 22 September 2016. The TV-Channel is called oe24TV of which the Logo of would be very similar to the logo of the internet portal oe24 of the newspaper.^[17]

1.  “Science News? Overview of Science Reporting in the EU” (PDF). EU. 2007. Retrieved 5 October 2013.
2. ^ “Austria: New circulation figures for the 1st half 2008”. Publicitas. 20 August 2008. Retrieved 8 October 2013.
3. ^ “Western Europe Media Facts. 2011 Edition” (PDF). ZenithOptimedia. Retrieved 6 March 2016.
4. ^ DWDL.de: Kooperation mit CNN – Österreich bekommt 24-Stunden-News-Sender.

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