Vitamin A shows promise in APLZebrafish modeling of atypical PML-RARA isoform from acute promyelocytic leukemia patient and its implications for clinical treatment.
We constructed a zebrafish model to explore how a unique version of the PML-RARA protein, linked to acute promyelocytic leukemia (APL), might respond to treatment with all-trans retinoic acid (ATRA). This model allowed us to examine whether ATRA, a derivative of vitamin A, could be effective for patients with atypical APL characteristics.
In our findings, we observed that the response of the new PML-RARA isoform to ATRA treatment was similar to classical isoforms seen in the condition. We also found that ATRA worked well in this model, leading to favorable results for the treated patient, who reached complete remission shortly after starting therapy with ATRA and arsenic trioxide (ATO).
These results highlight the promising potential of vitamin A derivatives in cancer treatment, especially in various forms of APL. It's encouraging to see that ATRA can lead to substantial recovery, further supporting its use in clinical settings alongside other therapies.
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Promising APL treatment outcomes observedLong-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia.
We aimed to understand the effectiveness of a combination treatment involving all-trans retinoic acid (ATRA), arsenic trioxide (ATO), and gemtuzumab ozogamicin (GO) for patients with acute promyelocytic leukemia (APL). This was a phase 2 trial involving newly diagnosed APL patients, where ATRA and ATO were used to induce remission.
The results were promising, as we observed a complete remission rate of 93.8% among the participants. Furthermore, 97.1% of those who achieved remission had no measurable residual disease, indicating a strong initial response to the treatment regimen.
Over a median follow-up of about 62 months, the 5-year survival rates were also impressive, with event-free survival at 92.4%, disease-free survival at 93.6%, and overall survival at 93.1%. We noted some side effects, including elevated liver enzymes and infections, but there were no severe complications like veno-occlusive disease.
While the study highlights the benefits of ATRA in this combination treatment, we must clarify that we cannot specifically isolate the effect of vitamin A, as it was part of a broader therapeutic approach. Nonetheless, the combination of ATRA with other agents showed significant success in treating APL, reinforcing the importance of multifaceted cancer therapies.
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Nanoparticle-assisted targeted cancer therapyNanosecond Laser Pulses Facilitating Efficient and Specific Cell Killing with Doxorubicin-Loaded Gold Nanoparticles Targeted to the Folate Receptor.
We explored the use of nanosecond laser pulses combined with doxorubicin-loaded gold nanoparticles (AuNPs) to target folate receptor-positive cancer cells. This innovative method allowed for the efficient release of the drug while inducing localized cell damage through thermal effects.
By testing different nanoparticle concentrations and laser settings, we observed near-complete tumor cell destruction in pinpointed areas, sparing nearby healthy cells. The results emphasized the potential of this approach for developing safer and more effective cancer therapies.
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Targeted nanogels boost cancer therapyPreparation of targeting nanogels for controlled delivery of 5-aminolevulinic acid triggered by matrix metalloproteinases as photodynamic therapy.
We examined a new approach to enhance cancer treatment by developing targeted nanogels using folic acid to deliver 5-aminolevulinic acid (5-ALA) more effectively.
By using special nanoparticles, we found that these nanogels significantly improved the delivery of 5-ALA to tumor cells, enhancing the effectiveness of photodynamic therapy.
Our in vivo experiments indicated that these nanogels notably reduced the growth of skin cancer.
Overall, this innovative delivery system shows great promise in boosting the therapeutic effects of 5-ALA against skin cancer.
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Fenretinide shows promise against AMLFenretinide targets GATA1 to induce cytotoxicity in GATA1 positive Acute Erythroid and Acute Megakaryoblastic Leukemic cells.
We observed that certain types of Acute Myeloid Leukemia (AML), specifically acute erythroleukemia and acute megakaryocytic leukemia, have a concerningly short median survival and limited effective treatment options. Our exploration focused on understanding the role of the transcription factor GATA1, which is crucial for the survival of cells in these leukemia subtypes. Remarkably, we discovered that a compound known as Fenretinide (or 4-HPR), a synthetic derivative of vitamin A, can target and induce loss of GATA1 in these AML cells.
As we delved into the study, we found that treating M6 AML cells with low concentrations of 4-HPR led to significant cytotoxic effects, akin to reducing GATA1 levels through genetic methods. This indicates that 4-HPR could act similar to a targeted therapy, directly impacting the survival of these cancer cells. Further, we were encouraged to see that 4-HPR not only performed effectively on its own but also enhanced the effectiveness of existing treatments like Azacytidine and Venetoclax, which typically struggle against drug resistance.
Our findings suggest that 4-HPR might represent a promising therapeutic avenue for patients with M6 and M7 AML, paving the way for its potential inclusion as a standard treatment option in the near future. The safety profile of Fenretinide, established through numerous clinical trials, further strengthens the case for its application in the combat against these aggressive forms of leukemia.
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