Aura Quismas Tangerine Rat🍊🐀

El Guadalquivir a su paso por Córdoba supera el umbral naranja El río Guadalquivir ha vuelto a superar el umbral naranja a su paso por la ciudad de Córdoba a las 5:00 de este miércoles, según la información de la Confederación Hidrográfica del Guadalquivir (CHG). El río baja a una altura de 2,142 metros a su paso por la ciudad en una jornada en la que hay aviso amarillo por viento en la Campiña y naranja en la Subbética. En esta zona de la provincia cordobesa, además, está activo el aviso amarillo por lluvias. Hay que recordar que el nivel rojo, el máximo que contempla la CHG, está situado en los 2,5 metros.

DIRECTO | El Guadalquivir a su paso por Córdoba supera el umbral naranja dozz.es/wjtn85

local buny barista

SÍ, LO SIENTO JOER xDDD

Mi tía no sé por qué le gusta contarme noticias negativas del día. Que sí, que yo entiendo que lo complicado puede ser quedarte con lo bueno, pero cuéntame otra cosa, que ya sé que Trump se está cargando su país.

La vida es un privilegio. Suscribo cada palabra, cada idea, cada pincelada que Carlos Hernández da en su carta postuma. Leedla, por favor. Me parece que ya sé qué voy a meter en el buzoneo a mis vecinos.

🦭🦭🦭🦭

Well now, would you look at that? A massive, 4-YEAR-LONG study of NEARLY 30 MILLION people in France found that individuals who received a COVID-19 mRNA vaccine had a 74% LOWER risk of death from severe COVID-19 compared to unvaccinated individuals and ZERO increased risk of all-cause mortality.

“art” is an anagram of “rat”. think about that before you look at a beautiful painting

🌧️El tren de la lluvia no para. Especial atención a Andalucía, donde hay aviso rojo en el entorno de Grazalema.
❄️La cota de nieve empezará baja esta próxima madrugada en la meseta norte, pero pronto subirá.
🌪️El viento también será intenso en Andalucía.

within the field. These results are compelling enough to justify moving towards carefully designed human studies for further validation, safety studies, and, if regulatory approvals and funding align, early-phase human clinical trials.

The study demonstrates a potential treatment in experimental models, not in people- yet. However, independent cancer researchers not involved in the study have noted that durable responses without relapse are exceptionally rare in pancreatic cancer models, making the results particularly significant

Figure 4. Pharmacological targeting of mouse orthotopic tumors.

Figure 5. Combined inhibition of KRAS, EGFR and STAT3 in orthotopic and GEM mouse tumor models.

Figure 6. Therapeutic effect of the combined inhibition of KRAS, EGFR and STAT3 in Patient-Derived Xenografts.

patients and grown in the laboratory. The important finding of the study was that, unlike traditional chemotherapy, which often causes severe side effects, the triple-drug combination showed low toxicity in animals. The mice tolerated the treatment well, a crucial factor if the therapy is ever to

move into human trials. Researchers did note that this is the FIRST time a complete, durable response with low toxicity has been achieved in these experimental models.

Figure 1. Differential response of mouse PDAC tumors to Raf1 and Egfr ablation.

Figure 2. STAT3 mediates tumor resistance to Raf1 and Egfr ablation.

Figure 3. Therapeutic effect of concomitant ablation of Raf1, Egfr and Stat3 in orthotopic pancreatic tumors.

The results show that in mouse models designed to closely mimic human pancreatic cancer, tumours completely disappeared. Even more striking, they did not return for more than 200 days after treatment stopped. The same effect was seen in genetically engineered mice AND in tumours taken from HUMAN

In simpler terms, this combination therapy cut the engine, sealed the exits, and disabled the emergency backup, all at the SAME TIME.

So, why is this different?

KRAS has long been considered “untouchable.” This approach shut it down completely- at least in experimental models.

•The first drug, daraxonrasib, blocks the main KRAS growth signal.

•The second, afatinib, shuts down EGFR and HER2 pathways, which cancers often use as escape routes.

•The third, SD36, disables STAT3, an stress-response system that helps tumour cells survive treatment.

a drug already approved for lung cancer, with a protein degrader, resulting in tumours disappearing WITHOUT significant side effects in THREE DIFFERENT experimental models. Essentially, instead of hitting one target, researchers attacked the cancer from three directions at once:

In pancreatic cancer, this ability to “rewire” itself is a major reason single-drug treatments fail. The key to THIS breakthrough lies in avoiding the resistance that appears when the KRAS oncogene molecular pathway is blocked at a single point. The CNIO team combined an experimental KRAS inhibitor,

struggled to block it. Relatively new KRAS-blocking drugs, including one called daraxonrasib, have shown promise and can extend survival. But cancer finds ways to grow. When one pathway is blocked, tumours often activate alternative routes- molecular detours that let them survive and return.

cancer has remained one of oncology’s toughest challenges. At the core of most pancreatic cancers lies a faulty gene called KRAS, which constantly sends signals telling cancer cells to grow and divide. KRAS mutations are found in over 90% of pancreatic cancers. For decades, researchers have

long-lasting tumour regression. In Spain, more than 10,300 cases of this type of cancer are diagnosed each year, with a five-year survival rate of less than 10%. Standard chemotherapy often slows the disease only briefly, because tumors rapidly adapt and find new ways to grow. This is why pancreatic

tumors in experimental models and prevent them from recurring using triple combination therapy. The results, published in the journal Proceedings of the National Academy of Sciences (PNAS), show that simultaneously targeting three key points of the KRAS oncogene molecular pathway achieves

Pancreatic cancer is one of the most aggressive tumors with the worst prognosis, partly because of the rapid emergence of resistance to treatment. But a new study from the Spanish National Cancer Research Centre (CNIO), led by Dr. Mariano Barbacid, reveals that it is possible to eliminate pancreatic

Who Is Dr. Mariano Barbacid? Spanish Scientist Leading The Most Promising Pancreatic Cancer Breakthrough Yet Dr. Mariano Barbacid, a pioneering Spanish cancer scientist, alongside his team have eliminated aggressive pancreatic tumours in mice using a triple-drug therapy targeting the KRAS pathway. While not ...

Researchers managed to overcome tumors using a triple combination therapy, which also avoids the common problem of treatment resistance. Currently, drugs for pancreatic cancer lose effectiveness within months because the tumour becomes resistant.
• www.timesnownews.com/world/who-is...

Significance The development of RAS inhibitors represents a major advance in the treatment of KRAS-driven pancreatic ductal adenocarcinoma (PDAC). RAS(ON) inhibitors such as daraxonrasib (RMC-6236) have led to significant improvements in survival compared to historical data. Unfortunately, the rapid onset of tumor resistance has thwarted their therapeutic benefit. This study describes a triple combination therapy made of daraxonrasib along with afatinib, an irreversible EGFR/ HER2 kinase inhibitor and SD36, a selective STAT3 PROTAC that induces the robust regression of experimental PDACs and avoids the onset of tumor resistance. This triple combination is well tolerated in mice. Taken together, these studies open the road to design novel combination therapies that may improve the survival of PDAC patients.

Abstract Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest cancer survival rates. Recent studies using RAS inhibitors have opened the door to more efficacious therapies, although their beneficial effect is still limited mainly due to the rapid appearance of tumor resistance. Here, we demonstrate that genetic ablation of three independent nodes involved in downstream (RAF1), upstream (EGFR), and orthogonal (STAT3) KRAS signaling pathways leads to complete and permanent regression of orthotopic PDACs induced by KRAS/TP53 mutations. Likewise, a combination of selective inhibitors of KRAS (RMC-6236/daraxonrasib), EGFR family (afatinib), and STAT3 (SD36) induced the complete regression of orthotopic PDAC tumors with no evidence of tumor resistance for over 200 d posttreatment. This combination therapy also led to significant regression of genetically engineered mouse tumors as well as patient-derived tumor xenografts (PDX) in the absence of tumor relapses. Of importance, this combination therapy was well tolerated. In sum, these results should guide the development of new clinical trials that may benefit PDAC patients.

The study has been published in PNAS (Proceedings of the National Academy of Sciences). YES, it is PEER-REVIEWED.
• www.pnas.org/doi/10.1073/...

NOTE: THIS IS PRECLINICAL. Results were also shown in tumors taken from HUMAN patients and grown in the laboratory.

🧪🧵⬇️

GOOD NEWS! For the FIRST time ever, researchers have developed a targeted combination therapy that has successfully AND completely ELIMINATED KRAS-driven pancreatic tumors in experimental models. Tumors regressed COMPLETELY with NO recurrence OR major side effects. Let’s talk about that!

Last time I was streaming in 2020, and many folks remember this time as the coziest. Sooo...

⚡I decided to bring back my ART SERVER not only for sharing stream announcements & updates, but for folks & mutuals that would like to get to know each other more!

Feel free to join 🧡
discord.gg/SD8D9C4B

¿Os acordáis de la modelo mexicana aquella que gritaba que se comían humanos en las fiestas de las élites, que la ingresaron en un psiquiátrico y que luego desapareció y no se supo más de ella? Pues parece que no iba tan desencaminada.