receptors, resulting in the effect that we have seen in the cancer cells in vitro and in vivo. Further investigation is required to understand the signalling pathways which might be altered as a result of knocking down RAMP3. The results shown here are not without precedent. One group in particular has focused on the use of anti-AM strategies for cancer treatment. Ouafik’s group in France has performed several similar studies, although in some papers the details are sketchy so a full interpretation of the results is difficult. The group used subcutaneous xenograft models for their studies and their treatment groups either received systemic doses of antibodies to CLR, RAMP2 or RAMP3 or a mixture of those. The data on dosage and effects is not clear from the articles, and some animals died, possibly as a result of the effects of a physiological AM blockade (either by a blockade of CLR or AM1 receptors). However, the results indicate that a RAMP3 polyclonal antibody is effective in reducing tumour volume, though less effective than a more comprehensive AM blockade via CLR and AM1R. Further studies show that the injection of these agents into the tumours leads to reductions in tumour volume growth (, ). Finally, a Japanese group has shown that the AM truncated peptide antagonist AM22-52 reduces tumour volume if injected into the tumour mass. The pancreatic cancer cells PCI-43 were injected in SCID mice. 8 days after the cancer cells were injected subcutaneously into the right flanks of the mice, AM22-52 was injected directly into the tumour (intratumoral injection). The injection of AM22-52 continued to day 17. The result showed that tumour formation was inhibited significantly compared to the control (PBS). Also, the diameter of the blood vessels of the formed tumours was reduced hugely compared to control group (). This data illustrates that AM is important for the in vivo tumour formation of pancreatic cancer cells.
receptors, resulting in the effect that we have seen in the cancer cells in vitro and in vivo. Further investigation is required to understand the signalling pathways which might be altered as a result of knocking down RAMP3. The results shown here are not without precedent. One group in particular has focused on the use of anti-AM strategies for cancer treatment. Ouafik’s group in France has performed several similar studies, although in some papers the details are sketchy so a full interpretation of the results is difficult. The group used subcutaneous xenograft models for their studies and their treatment groups either received systemic doses of antibodies to CLR, RAMP2 or RAMP3 or a mixture of those. The data on dosage and effects is not clear from the articles, and some animals died, possibly as a result of the effects of a physiological AM blockade (either by a blockade of CLR or AM1 receptors). However, the results indicate that a RAMP3 polyclonal antibody is effective in reducing tumour volume, though less effective than a more comprehensive AM blockade via CLR and AM1R. Further studies show that the injection of these agents into the tumours leads to reductions in tumour volume growth (, ). Finally, a Japanese group has shown that the AM truncated peptide antagonist AM22-52 reduces tumour volume if injected into the tumour mass. The pancreatic cancer cells PCI-43 were injected in SCID mice. 8 days after the cancer cells were injected subcutaneously into the right flanks of the mice, AM22-52 was injected directly into the tumour (intratumoral injection). The injection of AM22-52 continued to day 17. The result showed that tumour formation was inhibited significantly compared to the control (PBS). Also, the diameter of the blood vessels of the formed tumours was reduced hugely compared to control group (). This data illustrates that AM is important for the in vivo tumour formation of pancreatic cancer cells.
Emad%27s%20Thesis%20final%20after%20correction%201-12-2015%20last.docx