In our study of concurrent bortezomib and whole brain irradiation, we administe

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 In our study of concurrent bortezomib and whole brain irradiation, we administe Empty In our study of concurrent bortezomib and whole brain irradiation, we administe

Post  jy9202 on Thu Jan 02, 2014 5:00 am

Interestingly it also caused paraptosis, forma tion of cytoplasmic vacuoles and apoptosis in multiple cancer cell types, On the contrary, MG 132 induced cell death was partially attenuated on treatment with au tophagy inhibitor, 3 MA, which ensures the importance of autophagy in PI, triggered cell death. However, induction of autophagy oral JAK 阻害剤 is supposed to be primarily a defense mech anism to bypass the incidence of cell death after PI treat ment, still it remains to be a crucial event in PI induced growth arrest of cancer cells, These studies clearly indicate that the intricate mechanisms of associ ation of ER stress, autophagy and resistance to PI therapy needs further investigation. Conclusions and future perspectives Development of chemoresistance against PIs and its in efficacy against many solid cancers necessitates a thorough assessment of the treatment strategies involving PIs.

Though not much has been explored in this context but certain reports suggest that induction of autophagy post PI treatment is a major cause of resistance to PI therapy, Therefore LDE225 構造 exploring synergistic drug combina tions with PIs for effectively combating chemoresistance and limitations of targeted therapy could be a logical the rapeutic strategy. As discussed above proteasome inhibitor induced cell cycle arrest is attributed to modulation of one or more pathways. Therefore, the combination of PIs along with the modulators of one of these signaling path ways, may possibly be explored for their therapeutic po tential in PI resistant cancer types.

Already some reports have indicated the potential of PIs in combination with different class of compounds, Combination of Bortezomib and autophagy inhibitor, Bafilomycin A1 in creases the purchase LY2157299 cytotoxic effects against multiple myeloma cells. Similarly, combination of PIs and ER stress inhibitor, salubrinal potentiates toxicity in therapy resistant multiple myeloma cells, Recent studies also suggest the syn ergy between HDAC inhibitors and PIs against multiple myeloma cell lines and have shown promising re sults in clinical trials, PIs in combination with HDAC inhibitors also induce cell cycle arrest via NFkB and ROS pathways, These findings provide new insights for combination therapy of HDAC inhibitors and PIs, Bortezomib has also been tested in combination with Nel finavir, an HIV protease inhibitor and the results have indicated induction of ER stress, cell cycle arrest in cer vical cancer cells, Several other combinations with PIs worked out on different cancer cells given encouraging results for combination therapy is summarized in Additional file 1: Table S1.

However, there is an ever in creasing need for such synergistic combinations with drugs from the synthetic and natural source for effectively targeting cancer cells with PI resistance. Radiotherapy is one of the most important modalities for the management of cancer. However, despite pro gress in radiation technology and significant gains achieved with the use of combined radio chemotherapy, there is a substantial proportion of patients that fail to achieve long term control, The latter provides a strong rationale for combining molecular targets with radiation to improve patient outcome.


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