2 goda nyheter i en och samma studie. Jag körde en vanlig googlesökning för en stund sen,och fick napp.Ett dubbelnapp skulle det visa sig. I forskningsrapporten nedan hittade jag nämligen studier som handlade om MIN cancer : Diffust storcelligt B-cellslymfom (DLBCL = Diffuse Large B-Cell Lymphoma).Att forskare nu hittat ett effektivare läkemedel mot min svårbotbara cancer är ju bara för underbart.Forskarna testade substansen Avanbulin tillsammans med andra vanliga cancerläkemedel som ingår i mixen jag fick, R-Chop, och erhöll bra resultat.Skulle det värsta inträffa för undertecknad,återfall,finns nu ett effektivt läkemedel att tillgå.
Studien är denna :
Abstract 2575: Avanbulin, the active moiety of the tumor checkpoint controller lisavanbulin (BAL101553), has anti-lymphoma activity
15 June 2022
Abstract
Background: Avanbulin (BAL27862) is a microtubule-targeting agent (MTA) that promotes tumor cell death by modulating the spindle assembly checkpoint. Preclinical studies in glioblastoma (GBM) have shown that avanbulin is also active in human cancer cells resistant to other MTAs used in the clinic. Lisavanbulin (BAL101553) is a water-soluble, oral, lysine prodrug of avanbulin, currently in phase 1/2 for patients with recurrent GBM and, in combination with radiotherapy, for newly diagnosed GBM patients. Preclinical studies and clinical signals have also suggested an association between lisavanbulin activity and expression of microtubule plus-end binding protein (EB1). MTAs are active agents for lymphoma patients, as exemplified by the inclusion of vincristine in the R-CHOP regimen, standard treatment for diffuse large B cell lymphoma (DLBCL). Thus, our aim was to evaluate avanbulin, the active moiety of lisavanbulin, for its potential anti-lymphoma activity.
Methods: Lymphoma cell lines derived from activated B cell like (ABC) and germinal center B cell type (GCB) DLBCL were exposed to increasing doses of avanbulin; cell proliferation was measured with MTT. Apoptosis induction was performed with annexin V staining on cells incubated in a live cell imaging system (Incucyte) treated with 5, 10, 20 or 40nM avanbulin. Images were taken every 4h for 72h. Cell cycle analysis was performed after 24, 48 and 72h of drug exposure at 20nM.
Results: 26 DLBCL cell lines, treated for 72h with increasing avanbulin doses, showed high anti-proliferative activity of the compound, with a median IC50 = 11nM. No differences in terms of IC50 were observed comparing ABC (n=8) to GCB (n=18) DLBCLs, nor based on MYD88, TP53 and BCL2 status. Cell lines with MYC translocation were less sensitive than the ones without translocation. All lymphoma cell lines exhibited high EB1 RNA expression, with no correlation with sensitivity to avanbulin.Live cell imaging demonstrated a strong apoptosis induction in 15 out of 17 cell lines tested at 20 and 40nM. Among the 15 cell lines undergoing apoptosis, 8 cell lines already showed an apoptosis induction within 24h of drug exposure, 6 lines between 24 and 48h and 1 line after 48h exposure. These data confirmed the high activity of avanbulin already seen with the MTT assay.Cell cycle experiments performed at 24, 48 and 72h confirmed the strong cytotoxic effect of avanbulin in 4 DLBCL cell lines, including 2 ABC (OCILY3 and TMD8) and 2 GCB (SUDHL5 and SUDHL16) lines. Sub-G0 accumulation was already present at 24h in all 4 cell lines tested, with an increase over time. Especially at 24h, where we also observed a G2-M arrest in 3 out of 4 cell lines.
Conclusions: Our data demonstrate the high cytotoxic anti-lymphoma activity of avanbulin, suggesting a potential activity of its prodrug lisavanbulin in lymphoma patients.
SWITZERLAND
- University of Fribourg
ITALY
- Institute of Biophysics, National Research Council of Italy, Genoa
- Department of Civil Engineering and Architecture, University of Pavia
Tack för gräv!(igen) hur ser det ut med insamlingen till köp av holomonitor ?
SvaraRaderaInsamlingen avstannade tack vare att jag befann mig mitt i min cellgiftsbehandling. Orken räckte inte att fortsätta promota insamlingen.
RaderaKollade swishkontot precis och insamlingen är uppe i 41 050 kr.
Finns intresse att bidra gör man det på 0736900781.
Jag har kontakt med en vass cancerforskare knuten till Karolinska Institutet som är nyfiken på instrumentet. Men beloppet vi skramlat ihop räcker inte långt för att sponsra hans forskningsavdelning med en HoloMonitor. Så jag har fler funderingar om hur gå i land med detta projekt.När jag vet mera kommer jag lägga ut info på bloggen.
Tanken är att alla som bidragit till insamlingen ska få ett stort TACK i någon form när jag gått i land med detta.
Mvh the99
Jag får korrigera mig själv.Minnet är kort ibland.
RaderaJag mådde skitdåligt under större delen av min cellgiftsbehandling.
Orken och engagemanget var därefter.
Man vill gärna glömma denna jobbiga period.
Mvh the99