Publications by authors named "Sime Brkic"
Article Synopsis
- * Researchers found that MPN cells developed resistance to CHZ868, as evidenced by increased drug resistance and activation of the MAPK signaling pathway, while the JAK2-STAT3/5 pathways remained suppressed.
- * The results suggest that targeting both AXL and the MAPK pathway could enhance the effectiveness of JAK2 inhibitors, indicating a potential new treatment strategy for MPN by addressing this acquired resistance mechanism.
Article Synopsis
- Immune surveillance plays a crucial role in preventing tumor development, but gliomas (a type of brain tumor) have mechanisms to escape immune detection that are not fully understood.
- Research shows that glioma cells can grow without being affected by the immune system by lowering Notch signaling, which reduces the expression of important immune markers and allows for the growth of suppressive immune cells that promote tumor growth instead of attacking it.
- The study reveals that when Notch signaling is inhibited, glioma cells not only avoid immune responses but also become more aggressive by upregulating oncogenes and downregulating genes associated with cell stability, highlighting how gliomas manipulate their environment to evade immune control.
Article Synopsis
- Chronic neutrophilic leukemia (CNL) is driven by CSF3R mutations, particularly T618I and W791*, but the role of truncating mutations needs more clarity.
- This study examined how both germline and somatic mutations contribute to CNL progression and the potential transformation into acute leukemia, using a 33-year-old patient as a case study.
- Findings showed that the T618I mutation and W791* truncation are on the same allele, and CNL can evolve into mixed phenotype acute leukemia (MPAL), highlighting the complexity of clonal evolution and increased mutation susceptibility.
Article Synopsis
- Myeloproliferative neoplasms (MPN) exhibit abnormal JAK2 signaling, and while JAK2 inhibitors help treat them, the MAPK pathway often compensates and limits their effectiveness.
- The study proposed that targeting both JAK2 and ERK1/2 could improve treatment, showing that ERK1/2 deficiency reduced MPN symptoms and the Jak2V617F clone in models and patient samples.
- Combining JAK2 and ERK1/2 inhibitors demonstrated a significant reduction in cancer cell proliferation and various MPN symptoms, indicating a promising new therapeutic strategy for treating MPN.
Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders with dysregulated myeloid blood cell production and propensity for transformation to acute myeloid leukemia, thrombosis, and bleeding. Acquired mutations in , , and converge on hyperactivation of Janus kinase 2 (JAK2) signaling as a central feature of MPN. Accordingly, JAK2 inhibitors have held promise for therapeutic targeting.
View Article and Find Full Text PDFConstitutive JAK2 signaling is central to myeloproliferative neoplasm (MPN) pathogenesis and results in activation of STAT, PI3K/AKT, and MEK/ERK signaling. However, the therapeutic efficacy of current JAK2 inhibitors is limited. We investigated the role of MEK/ERK signaling in MPN cell survival in the setting of JAK inhibition.
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- Vascular endothelial growth factor (VEGF) regulates angiogenesis primarily through sprouting, but its application in ischemic muscle results in intussusception, an alternative process where blood vessels split.
- Researchers have identified ephrinB2/EphB4 signaling as a critical player in this intussusceptive angiogenesis, influencing how blood vessels expand and form capillary networks under varying VEGF doses.
- The study highlights that EphB4 fine-tunes VEGF's effects without blocking its action and points to its potential as a therapeutic target for improving vascular growth in muscle tissue.
Aim: Determine the levels of expression of pluripotency genes OCT-4 and SOX-2 before and after osteogenic differentiation of human mesenchymal stem cells (hMSCs).
Methods: Human MSCs were derived from the bone marrow and differentiated into osteoblasts. The analyses were performed on days 0 and 14 of the cell culture.
Article Synopsis
- VEGF plays a crucial role in therapeutic angiogenesis, but its effectiveness is compromised by the need for short-term delivery due to safety concerns, leading to unstable new blood vessels.
- Research using transduced myoblasts in SCID mouse muscles revealed that low doses of VEGF promote faster vessel stabilization, while high doses delay it, without affecting pericyte coverage.
- The study found that high VEGF levels inhibit endothelial Semaphorin3A expression, disrupting the recruitment of specific monocytes necessary for vessel stabilization, but Semaphorin3A treatment can counteract this effect even with high VEGF doses.
Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery.
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