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Wang M.,Peter MacCallum Cancer Center | Wang M.,University of Melbourne | Wang M.,Royal Melbourne Hospital | Busuttil R.A.,Peter MacCallum Cancer Center | And 8 more authors.
World Journal of Gastroenterology | Year: 2016

Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an us against them model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy-the tumour cell. © The Author(s) 2016.


Multiple myeloma is a haematological disorder of malignant plasma cells. Interleukin-6 (IL-6) is a potent growth factor for the proliferation of these cells. Vincristine as a chemotherapeutic agent is used mainly in combination with other chemotherapeutic substances in the treatment of different haematological disorders. Viscum album QuFrF (VAQuFrF) extract is an experimental drug that is not used in the treatment in tumour patients. It contains 2000 ng lectin and 10 μg viscotoxin in 10 mg extract. In this study, the effects of VAQuFrF extract were compared with those of vincristine in six human multiple myeloma cell lines (Molp-8, LP-1, RPMI-8226, OPM-2, Colo-677, and KMS-12-BM) using an in vitro model. As parameters, the IL-6 production, proliferation, apoptosis/necrosis, and cell cycle phases of the cells were taken. To measure the IL-6 production, apoptosis/necrosis, and cell cycle phases, the substances were tested in dose ranges of 10, 50, and 100 μg/106 cells. To measure the proliferation of the cells, the substances were tested in dose ranges of 1, 5, and 10 μg/105 cells. The profile of the antitumour effects of the two substances is identical. (1) Neither VAQuFrF extract nor vincristine produced IL-6 in any cell line. (2) Both substances inhibited the proliferation of the cells (cytostatic effect), arrested the cell cycle phases, and increased the number of apoptotic/necrotic cells (cytocidal effect). At a dose of 10 μg/105 cells, VAQuFrF more effectively inhibited the proliferation than vincristine (p < 0.01) in the cell lines Molp-8, LP-1, and RPMI-8226. (3) VAQuFrF affected the tumour cells mainly via cytostatic effect. Vincristine had a clear cytocidal effect. These findings indicate that VAQuFrF extract could be a novel drug in the treatment of multiple myeloma. ©2010 with author. Published by TheScientificWorld.


Quach H.,Peter MacCallum Cancer Center | Quach H.,University of Melbourne | Quach H.,Haematology Immunology Translational Research Laboratory | Ritchie D.,Peter MacCallum Cancer Center | And 9 more authors.
Leukemia | Year: 2010

Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-proliferative effects. Their development was facilitated by an improved understanding in myeloma (MM) biology and initiated a profound shift in the therapeutic approach towards MM. Despite the diverse effects of IMiDs in vitro, the relative contribution of each effect towards their ultimate anti-MM activity is still unclear. Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes. Although the co-stimulatory effects on T and NK cells have been heralded as a unique and important property of IMiDs towards enhancing anti-MM immune activity, these in vitro effects have yet to be firmly corroborated in vivo. Much is yet to be elucidated regarding the complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in MMthe understanding of which is necessary to facilitate optimal manipulation of these drugs in future MM management. © 2010 Macmillan Publishers Limited All rights reserved.


LONDON (Reuters) - French drugmaker Sanofi has poached one of AstraZeneca's top scientists to be its new research head in another high-profile departure for the British drugmaker. Sanofi said on Tuesday that Yong-Jun Liu had been appointed as head of research with effect from April 1, reporting to Elias Zerhouni, the group's president of global research and development. Liu, a specialist in immunology with more than 250 published articles in leading academic journals, currently heads up research at AstraZeneca's MedImmune biotechnology division, a position he has held since 2014. Zerhouni said his appointment would help the transformation of Sanofi from a pharmaceutical into a biopharmaceutical company, with a strong research presence in cutting-edge biotechnology. Prior to that he led program at Baylor Research Institute and the MD Anderson Cancer Center, where he was founding director of the Cancer Immunology Research Institute. His decision to leave AstraZeneca follows the exit last June of Briggs Morrison, the company's former chief medical officer and head of late-stage drug development, and respiratory and inflammatory medicines head James Ward-Lilley. An AstraZeneca spokesman declined to comment on his move. AstraZeneca is going through a transition as older drugs lose patent protection and it invests heavily in new medicines, especially in the field of cancer immunotherapy. It has a promising pipeline of experimental drugs but has also suffered some recent setbacks, including last week's failure of its marketed heart drug Brilinta as a treatment for stroke patients and earlier disappointing results with a drug to treat lung and abdominal cancer mesothelioma. Sanofi, meanwhile, is seeking to rejuvenate its early-stage pipeline and Zerhouni said Liu's experience in immunology, oncology and translational medicine would be "vital assets" for this task. "He fits perfectly for us at this time," Zerhouni said in a telephone interview. "We have the luxury of a full late-stage pipeline and therefore we can step back and invest for the long term." Oncology is a particular priority. Sanofi may have missed the first wave of immunotherapy drugs that help fight tumors by removing brakes on the immune system, but Zerhouni hopes to "leapfrog" forward by focusing on new approaches and testing multiple cancer drug combinations. "Immuno-oncology is just at the beginning of its development," he said. "Frankly, I think it won't be enough to just remove a checkpoint inhibitor because it is also important to activate the immune system."


French multinational pharmaceutical company SANOFI logo seen at their headquater in Paris, France, March 8, 2016. REUTERS/Philippe Wojazer More LONDON (Reuters) - French drugmaker Sanofi has poached one of AstraZeneca's top scientists to be its new research head in another high-profile departure for the British drugmaker. Sanofi said on Tuesday that Yong-Jun Liu had been appointed as head of research with effect from April 1, reporting to Elias Zerhouni, the group's president of global research and development. Liu, a specialist in immunology with more than 250 published articles in leading academic journals, currently heads up research at AstraZeneca's MedImmune biotechnology division, a position he has held since 2014. Prior to that he led programmes at Baylor Research Institute and the MD Anderson Cancer Center, where he was founding director of the Cancer Immunology Research Institute. His decision to leave AstraZeneca follows the exit last June of Briggs Morrison, the company's former chief medical officer and head of late-stage drug development, and respiratory and inflammatory medicines head James Ward-Lilley. AstraZeneca is going through a transition as older drugs lose patent protection and it invests heavily in new medicines, especially in the field of cancer immunotherapy. It has a promising pipeline of experimental drugs but has also suffered some recent setbacks, including last week's failure of its marketed heart drug Brilinta as a treatment for stroke patients and earlier disappointing results with a drug to treat lung and abdominal cancer mesothelioma. Sanofi, meanwhile, is seeking to rejuvenate its early-stage pipeline and Zerhouni said Liu's experience in immunology, oncology and translational medicine would be "vital assets" for this task.

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