For en melding!
Dette har jeg ventet på.
Prof. Hani Gabra er en stjerne.
Nå nærmer vi oss begynnelsen av en rekke skudd på mål. Her som i fotball er det rutine og erfaring som gjelder. 
5 Likes
Merittene er ikke noe å si på, men siste tids prestasjoner er ikke spesielt imponerende.
Sammenligningen med Tippeligaen er for beskjeden, vi er nok i La liga / Serie A.
Flere Fast track av FDA blandt dem i verdens styggeste kreft indikasjon. Samt en potensiell fot innenfor verdens værste pandemi i nyere tid. Veldig god PR.
2 Likes
Mesangioproliferative Kidney Diseases and Platelet-Derived Growth Factor–Mediated AXL Phosphorylation
Published: August 02, 2021
https://www.kidneymedicinejournal.org/article/S2590-0595(21)00167-9/fulltext (DOI)
IgA nephropathy (IgAN) is a common glomerular disease, with mesangial-cell proliferation as a major feature. There is no disease-specific treatment. Platelet-derived growth factor (PDGF) contributes to the pathogenesis of IgAN. To better understand its pathogenic mechanisms, we assessed PDGF-mediated AXL phosphorylation in human mesangial cells and kidney-tissue biopsy specimens.
Immunoprecipitation experiments indicated association of AXL and PDGF-receptor (PDGFR) proteins. An AXL-specific inhibitor (bemcentinib) partially blocked PDGF-induced cellular proliferation and reduced phosphorylation of AXL and PDGFR and the downstream signals (AKT1, ERK1/2).
PDGF-mediated signaling in mesangial cells involves transactivation of AXL. Finding appropriate inhibitors to block PDGF-mediated transactivation of AXL may provide new therapeutic options for mesangioproliferative kidney diseases, such as IgAN.
(Bemcentinib, also known as BGB324 or R428)
17 Likes
Acute Myeloid Leukemia Pipeline Drugs and Companies Insight Report: Analysis of Clinical Trials, Therapies, Mechanism of Action, Route of Administration, and Developments
Emerging therapies such as omab-B CD45 and Actimab-A CD33, Ficlatuzumab, Devimistat, BST236, Bemcentinib, Pracinostat, are expected to have a significant impact on the Acute Myeloid Leukemia market in the coming years.
4 Likes
Toppsjefen går på dagen i Bergenbio
Noen som kan, i korte trekk forklare hva evt utfall er?
Mest sannsynlig så er det avgåtte CEO som har innløst sine opsjoner, sist gang lånte han aksjer og solgte samme dag som varselet om innløsning ble publisert (dvs da slipper han kontant utlegg), og det er jo noen dager siden nå. Så enten har han allerede solgt noe eller alt, eller så har han aksjene klare for salg til en passende anledning . Tror neppe du vil se den posten bli lagt ut på best i åpnings
auksjonen 
1 Like
Hjertelig. Synes bare prisinga var så rar, men kan svært lite om det og. Antar dette da ikke vil påvirke kursen på noen måte?
Hver måned kårer jeg det jeg kaller Teksperter™ for noen av de mest populære investeringene våre
Det er de 3 medlemmene som har fått flest likes på innleggene sine de siste 90 dagene. Teksperter™ får også en unikt merke på profilen sin og et trofé-ikon ved siden av navnet sitt. Du kan bli Tekspert™ i flere aksjer/investeringer, og troféet vil bare vises i tråder der du er Tekspert™.
Her er denne månedens Teksperter™ og det mest likte innlegget deres fra de siste 90 dagene:
- @anon28800809 (592 likes)
- @vcp (168 likes)
- @Hayen (134 likes)
Resten av topp 10:
-
@Direkte (125 likes)
-
@Roc (89 likes)
-
@Scrivener (87 likes)
-
@Matadoren (54 likes)
-
@alfred_e_neuman (33 likes)
-
@Ekornet (31 likes)
-
@Mykle (30 likes)
Gratulerer!
AXL Inhibition Represents a Novel Therapeutic Approach in BCR-ABL Negative Myeloproliferative Neoplasms
Published online 2021 Aug 11
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357258/ (DOI)
BCR-ABL negative myeloproliferative neoplasms (MPNs) consist of essential thrombocythemia, polycythemia vera, and myelofibrosis. […] AXL, a member of the TAM family of receptor tyrosine kinases, mediates survival and therapy resistance of different myeloid cancers including acute myeloid leukemia and chronic myeloid leukemia. […] We found that AXL is abundantly activated in MPN cells and that its ligand growth arrest-specific gene 6 is upregulated in MPN patients. Pharmacologic and genetic blockade of AXL impaired viability, decreased proliferation and increased apoptosis of MPN cells. […] Consistently, the AXL inhibitor bemcentinib exerted additive effects with ruxolitinib via impaired STAT3, STAT5, and AKT signaling. […] our data indicate that AXL inhibition represents a novel treatment option in MPN warranting clinical investigation.
Our previous work in acute myeloid leukemia (AML) indicated that malignant hematopoietic cells induce upregulation of the AXL ligand GAS6 in the BM stroma to foster their growth and to induce therapy resistance. Using the small molecule AXL inhibitor bemcentinib (BGB324) we demonstrated therapeutic potential of AXL blockade in in vivo models of AML. Furthermore, we demonstrated GAS6-AXL signaling in chronic myeloid leukemia (CML) cell lines and patient samples and showed growth inhibition of CML cells by bemcentinib. Bemcentinib represents a well-tolerated, specific AXL inhibitor with clinical activity in AML and is currently under investigation in a phase 2 trial in AML and myelodysplastic syndrome (NCT03824080).
Furthermore, AXL expression represents a negative prognostic factor in multiple solid tumors. In non-small-cell lung carcinoma (NSCLC) and melanoma patients, AXL upregulation has been observed in patients with resistance to targeted therapies and in non-responders to immune checkpoint blockade. Bemcentinib treatment was shown to overcome resistance to different targeted therapies and to increase chemosensitivity in preclinical models of solid malignancies. Currently, bemcentinib is studied in combination with chemotherapy, immunotherapy, or targeted therapies in non-small cell lung cancer (NCT03184571, NCT02922777, NCT02424617), triple negative breast cancer (NCT03184558), pancreatic cancer (NCT03649321), glioblastoma (NCT03965494), malignant mesothelioma (NCT03654833), and melanoma (NCT02872259).
Bemcentinib reduces tumor growth in vivo
Encouraged by the in vitro data indicating therapeutic potential of Axl inhibition in BCR-ABL negative MPN cells, we decided to investigate the effects of bemcentinib in vivo. […] We found a 60% inhibition of tumor growth in mice treated with bemcentinib compared with control-treated mice. Thus, AXL inhibition significantly reduced tumor growth of MPN cells in vivo. […]
Bemcentinib prolongs survival and reduces spleen size in MPN in vivo
Next, we tested the efficacy of bemcentinib and concomitant AXL and JAK2 blockade in a systemic mouse model. […] One day after injection, mice were randomized into 4 groups and treated with vehicle, bemcentinib, ruxolitinib, or bemcentinib plus ruxolitinib. Combined treatment with both drugs resulted in prolonged overall survival compared with single drug-treated mice. […]
In summary, our data highlight AXL inhibition as a new therapeutic approach in MPN and support the need for clinical trials of bemcentinib.
14 Likes
Takk for deling 
Ser vel ut som dette er en annen type av blodkreft enn AML?
Myeloproliferative neoplasms (MPN) are a collection of blood cancers which include:
- Polycythemia Vera (PV) - overproduction of red blood cells
- Essential Thrombocythemia (ET) — Overproduction of platelets
- Myelofibrosis (MF) - Accumulation of fibers and scar tissue that hinders production of blood cells within the bone marrow MPN arises when a blood stem cell acquires a mutation such as JAK2V617F which makes the blood stem cell think it is always receiving growth hormones instructing it to make more blood cells. MPN can cause problems like an increased tendency to form blood clots, symptoms such as itching, headache, and fatigue. Also, MPN can sometimes progress to a leukemia.
There is no cure for MPN other than a bone marrow transplant. New therapies are currently being developed for MPN but we still have a long way to go.
1 Like
Litt repetisjon:
Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer
Published: 15 September 2021
https://www.mdpi.com/1422-0067/22/18/9953 (DOI)
Receptor tyrosine kinases (RTKs) are cell surface receptors that mediate a number of physiological responses and homeostasis. However, gene amplification, overexpression, and activating mutations of RTKs are often associated with cancer development, pro- gression, and metastasis and have served as pharmacological targets in cancer treatment. Axl belongs to the TAM (Tyro3, Axl, MerTK) subfamily of the RTKs. Physiologically, the Gas6/Axl pathway plays an important role in platelet aggregation and vessel integrity. Axl knockout in germ cells does not result in embryonic lethality. The growth arrest specific 6 (Gas6) protein belongs to the vitamin K-dependent family of proteins and is a high affinity ligand for Axl. Overexpression and activation of Axl are widely observed in various cancer types and have been implicated in multiple steps of cancer pathogenesis. In addition, high Axl expression and activation are associated with poor prognosis, outcome, and resistance to therapy in cancer patients. As such, the Gas6/Axl pathway has gained attention as a promising therapeutic target for drug development in multiple tumor types.
Axl was first isolated from chronic myelogenous leukemia cells in 1988.
Briefly, Axl is overexpressed in many cancer types and is associated with therapeutic resistance, poor clinical prognosis, and worse outcome. Axl also mediates key components of the metastatic cascade, including, but not limited to, epithelial-to-mesenchymal transition, migration and invasion, proliferation, survival, stemness, angiogenesis, and immunesion.
Bemcentinib (BGB324, R428)
Bemcentinib is a highly specific and selective Axl inhibitor with an IC50 of 14 nM in cellular assays. This agent has been widely studied in the laboratory in a variety of cancer models, including breast, prostate, lung, pancreatic, and ovarian cancer, and has been shown to decrease tumor cell migration, invasion, and colony forma- tion in vitro and impair primary tumor growth, immune cell infiltration, and metastasis in vivo. Axl inhibition alters the expression patterns of EMT markers, upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin, ZEB1, Snail, Slug, Twist, and MMP9. Furthermore, several studies have demonstrated that Axl inhibition reverses the therapeutic resistance of certain chemothera- pies. Axl has also been associated with immune evasion, and the systematic treatment of tumor-bearing mice with bemcentinib has led to a reduction in tumor-infiltrating host cells, most notably cells of the myeloid lineage
Bemcentinib entered clinical trials as the first Axl-specific inhibitor and is undergoing Phase I/II clinical trials for melanoma, non-small-cell lung cancer (NSCLC), mesothe- lioma, acute myeloid leukemia, glioblastoma, and pancreatic adenocarcinoma (Clinical Trial Identification Numbers: NCT02872259; NCT02922777; NCT03184571; NCT03654833; NCT03824080; NCT03965494; NCT03649321). A Phase II clinical trial of bemcentinib in combination with pembrolizumab for patients with triple-negative breast cancer has been completed, but the results are not yet available (Clinical Trial Identification #: NCT03184558).
10 Likes
Noen enkle begrep nan bør skjønne om man investerer i biotek:
mAB=monoklonalt antistoff (eng antibody), disse gis i sprøyte/infusjon. Ingen Mab-er gis som tablett (enda i hvert fall) pga fordøyelse😏
Bemcentenib er en tablett, regnes som et småmolekylært legemiddel
5 Likes