R-Cu treated GBM
Background We present a novel therapeutic approach to glioblastoma (GBM) that targets cell-free chromatin particles (cfChPs) released from dying GBM cells to aggravate the oncogenic phenotype of living GBM cells. cfChPs can be deactivated by oxygen radicals (OR) generated upon admixing the nutraceuticals Resveratrol (R) and Copper (Cu). Oral administration of R-Cu leads to generation of OR which are readily absorbed to deactivate cfChPs. Method Ten patients with glioblastoma awaiting surgery were administered tablets containing 5.6mg of Resveratrol (R) and 560ng of Copper (Cu) q.i.d.  for an average of 11.6 ± 5.37 days. Another ten patients who did not receive R-Cu acted as controls. A biopsy of the tumour tissues was taken at operation for analysis using confocal microscopy, immunofluorescence and transcriptome sequencing.  Results Confocal microscopy of tumour sections revealed copious presence of cfChPs in the tumour microenvironment (TME) that had been released from dying GBM cells. R-Cu treatment led to deactivation / eradication of cfChPs. Eradication of cfChPs from TME led to a highly significantly reduction in Ki-67 and nine hallmarks of cancer, six immune check-points and three stem cell biomarkers. Transcriptome sequencing detected marked upregulation of pro-apoptotic and down-regulation of anti-apoptotic genes. Also detected was down-regulation of PVRIG-2P, a homologue of immune checkpoint receptor PVRIG which is a functional analogue of PD-L1.  Conclusion These results suggest that cfChPs released into TME are global instigators of aggressive phenotype of glioblastoma which can be attenuated by a short course of R-Cu. Trials using long term treatment with R-Cu are warranted.
Background We present a novel therapeutic approach to glioblastoma (GBM) that targets cell-free chromatin particles (cfChPs) released from dying GBM cells to aggravate the oncogenic phenotype of living GBM cells. cfChPs can be deactivated by oxygen radicals (OR) generated upon admixing the nutraceuticals Resveratrol (R) and Copper (Cu). Oral administration of R-Cu leads to generation of OR which are readily absorbed to deactivate cfChPs. Method Ten patients with glioblastoma awaiting surgery were administered tablets containing 5.6mg of Resveratrol (R) and 560ng of Copper (Cu) q.i.d.  for an average of 11.6 ± 5.37 days. Another ten patients who did not receive R-Cu acted as controls. A biopsy of the tumour tissues was taken at operation for analysis using confocal microscopy, immunofluorescence and transcriptome sequencing.  Results Confocal microscopy of tumour sections revealed copious presence of cfChPs in the tumour microenvironment (TME) that had been released from dying GBM cells. R-Cu treatment led to deactivation / eradication of cfChPs. Eradication of cfChPs from TME led to a highly significantly reduction in Ki-67 and nine hallmarks of cancer, six immune check-points and three stem cell biomarkers. Transcriptome sequencing detected marked upregulation of pro-apoptotic and down-regulation of anti-apoptotic genes. Also detected was down-regulation of PVRIG-2P, a homologue of immune checkpoint receptor PVRIG which is a functional analogue of PD-L1.  Conclusion These results suggest that cfChPs released into TME are global instigators of aggressive phenotype of glioblastoma which can be attenuated by a short course of R-Cu. Trials using long term treatment with R-Cu are warranted.
tata memorial centre