Constantinos Zambirinis, MD, MRes, FSSO

Low-dose metformin requires brain Rap1 for its antidiabetic action Metformin lowers blood glucose by inhibiting Rap1 in ventromedial hypothalamic neurons that regulate glucose balance.

Metformin, the first line drug for Type 2 diabetes, has been used for 60 years without a clearcut mechanism of action. It turns out it's not just reducing glucose output from the liver. Metformin also works via the brain www.science.org/doi/10.1126/...

Human brain vascular multi-omics elucidates disease-risk associations Reid et al. develop MultiVINE-seq to map thousands of non-coding disease variants to genes in human brain vascular cells. Cerebrovascular disease variants compromise vessel integrity, whereas Alzheime...

Multi-omic underpinnings of Alzheimer's disease promote inflammation (particularly via T cells)whereas those for stroke relate to vascular integrity @cp-neuron.bsky.social
www.cell.com/neuron/abstr...

Endoplasmic reticulum stress responses in anticancer immunity Nature Reviews Cancer, Published online: 24 June 2025; doi:10.1038/s41568-025-00836-5The endoplasmic reticulum (ER) has a central role in mounting effective and durable antitumour immunity. In this Review, Hwang et al. outline how tumour-induced ER stress responses alter the function of intratumoural immune cells and the efficacy of immunotherapy, highlighting the potential of unfolded protein response-targeted interventions to improve cancer outcomes.

NEW content online!

Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread Garner et al. demonstrate that mammary tumors skew hematopoiesis toward myeloid development. Tumor-induced immunosuppressive programming of neutrophils begins early in hematopoiesis and progressively ...

Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread: @cp-cancercell.bsky.social www.cell.com/cancer-cell/...

Interesting preprint on TCR-pMHC prediction and functional validation, with a great thread! 👇🏼

By the Shumacher Lab

Risk of Colorectal Cancer Associated With Frequency of Colorectal Polyp Diagnosis in Relatives - @gastroenterology.bsky.social www.gastrojournal.org/article/S001...

A graphic showing that 50.6% of research projects with "LGBT" search terms have been cancelled. 45.8% of grants with "transgender" in the search terms have been cancelled. 45.5% of research grants with "vaccine hesitancy" have been cancelled. 3.4% grants with "HIV" or "AIDS" have been cancelled.

The US National Institutes of Health has terminated nearly 800 research projects at a breakneck pace, wiping out significant chunks of funding to entire scientific fields

Read the full story: https://go.nature.com/3EuFRPV

Inebilizumab for IgG4-Related Disease | NEJM Quick Take Video Summary from The New England Journal of Medicine — Inebilizumab for IgG4-Related Disease

For patients with IgG4-related disease, there are no approved therapies. Research findings on the efficacy and safety of inebilizumab ― a monoclonal antibody that targets and depletes CD19+ B-cells ― are summarized in a new Quick Take video. nej.md/421enZX

#MedSky #RheumSky

🚨 New: Spleen-resident macrophages (MMMs) can directly activate CD8+ T cells to fight tumors – independently of dendritic cells. They use a vacuolar MHC-I pathway & need Batf3 for this antitumor response.
🧠 A game-changer for immunotherapy?

🔗 www.cell.com/immunity/abs... @cp-immunity.bsky.social

Or upfront ablation, when appropriate... ;)

Terrible indeed!

Everyone should be supporting and advocating for MORE (not less) funding for research on such devastating diseases as Pancreatic Cancer, especially when their incidence is rising!...
@pancan.bsky.social @pancreaticcanuk.bsky.social @pce-europe.bsky.social @letswinpc.bsky.social

Couldn't agree more with this. Precision dosing is the way. Max tolerated dose treatment by default, can detrimental for some patients, especially those that rely to a bigger extent on immune-mediated tumor control, and whose immune system is crippled by MTD chemo.

Highlight #2 from #CCG2025

Ethical aspects of genomic data sharing, by Prof. Eva Winkler, @dkfz.bsky.social

✅ Patients willing to share data, especially with academia, but have concerns about what happens later on.
🔐Need solid data protection framework in place, and education of researchers etc.

Kicking off an exciting Clinical Cancer Genomics 2025 conference with an overview of national molecular profiling strategies of 6 EU countries. Important points:
-WGS provides prognostic info (not just actionable targets)!
-Need to more data on various ancestries
-Need to increase testing!
#CCG2025

Learn more about the APAChE study:

📄 Read the full results published in NEJM: nej.md/3IrM6T8
📄 Read the editorial by Philip J. Landrigan, MD: nej.md/48CvGSs
📺 Watch the interview with Dr. Landrigan: nej.md/41SCs6f

NB:
-The majority of patients were HR+ HER2-
-Only 1.2% TNBC and only 3.6% HER2+

Research summary page:

Omitting Sentinel-Node Biopsy in Small Breast Cancers | NEJM Quick Take Video Summary from The New England Journal of Medicine — Omitting Sentinel-Node Biopsy in Small Breast Cancers

Nice summary video by @nejm.org on the INSEMA trial

👉In T1/small T2 breast cancers with clinically negative axilla, omitting SLN Biopsy is non-inferior to performing it:

✅ est. 5y inv.DFS of 92% at 6 years median f/up
✅ signif. less lymphedema & arm pain/restriction

www.nejm.org/do/10.1056/N...

Chemical industry lobbyists will run chemical safety oversight at US EPA The Trump administration is putting lobbyists and attorneys from the petroleum and chemical industries into leadership positions at the US Environmental Protection Agency (EPA). Several of these indiv...

👇 Not promising at all... 😣

Chemical industry lobbyists will run chemical safety oversight at US EPA - The Lancet Oncology www.thelancet.com/journals/lan...

This is consistent with our 2021 @annsurgoncology.bsky.social paper on resectable PDAC showing better OS after metachronous Extrahepatic-only recurrence, vs Liver recur: link.springer.com/article/10.1...
👉 PDAC #organotropism informs on tumor biologic aggressiveness. @metastasisresearch.bsky.social

#REVIEW 🚨

Miriam Merad & Co ‪@sinaiimmuno.bsky.social‬
outline the molecular basis of #DendriticCell maturation and the mechanisms through which cancer impairs #DC maturation and consider the potential for DC-focused cancer #immunotherapeutics.
📖 ⬇️

Clinical Trials: At the Leading Edge of Progress Join PanCAN on Jan. 30, at 11 a.m. PT / 2 p.m. ET, for an educational discussion about pancreatic cancer clinical trials and new developments in the field. RSVP for the event here:…

In case you missed our live event covering the latest in #pancreaticcancer clinical trials, you can watch the full recording now at pancan.org/clinicaltrials2025 🔬💜 Learn from experts about the basics of clinical trials, what developments are on the horizon and how to find the right trial for you.

«Νιώθω την αγωνία, το “χνώτο” του θανάτου» Σε ηλικία 14 ετών έδωσε μάχη με επιθετικό σάρκωμα. Σήμερα είναι τελειόφοιτη Ιατρικής, με καθηγητή τον χειρουργό της.

Amazing story! www.kathimerini.gr/society/5634...

Ok let's see what this platform has to offer, given X's decline... :)