�Scientists in the UK and Finland have ascertained that a new combination of the chemotherapy dose doxorubicin and the bone-protecting drug
zoledronic acid, both of which are substantially cheaper than herceptin, stopped-up breast malignant neoplastic disease tumors growing in mice. Experts suggest that since both drugs are
already in manipulation, and if the combination proves effective and safe in human clinical trials, it should not subscribe to as long for it to be available as a modern treatment for patients.
The survey, which was funded by the Breast Cancer Campaign, was the work of Dr Penelope Ottewell and Dr Ingunn Holen from Sheffield University's
School of Medicine and Biomedical Sciences, plus other colleagues at Sheffield University and as well at the University of Kuopio in Finland. It is published in the 11
August 2008 issue of the Journal of the National Cancer Institute, JCNI.
Breast malignant neoplastic disease is ordinarily treated with a combination of drugs including chemotherapy to period tumors growing, and in cases of advanced cancer,
patients occupy a bisphosphonate to stopover bone red ink and protect against pain in the neck and weakness.
In their background information the researchers said that "test tube" experiments had already shown zoledronic acid enhanced the antitumour effects
of chemotherapy drugs, so they decided to see what effect it would have in living mouse models, either on its have, together, or in chronological sequence with the
chemotherapy agent doxorubicin.
For the study, the researchers induced breast cancer tumors in mice by injecting them with human white meat cancer cells and and so after 7 days they
injected them every week for 6 weeks with either (1) saline, or (2) doxorubicin, or (3) zoledronic vitriolic, or (4) doxorubicin and zoledronic vitriolic, or (5)
zoledronic acidulous followed 24 hours later by doxorubicin, or (6) doxorubicin followed 24 hours later by zoledronic sulfurous. There were about 8 or 9 mice in
each handling group.
Ottewell, Holen and colleagues then assessed the effect of the various treatments on tumor growth victimisation a kitchen range of methods, including measuring
tumor volume and rate of programmed tumor cell death (programmed cell death). They as well assessed the effect on bone.
The results showed that:
Treatment with doxorubicin or zoledronic acid alone, or zoledronic acid followed by doxorubicin 24 hours later, did not significantly decrease
neoplasm volume compared with saline.
Treatment with doxorubicin plus zoledronic acid produced significantly littler final tumor volumes than doxorubicin alone, zoledronic solitary, or
zoledronic acid followed 24 hours later by doxorubicin.
However, treatment with doxorubicin followed 24 hours later with zoledronic acid, "about completely abolished tumor growth".
Tumors from mice treated with doxorubicin followed by zoledronic acid showed more evidence of apoptosis or programmed cell death (using
front of caspase-3-positive cells as a bar) than tumors from mice treated with saline, with zoledronic virulent alone, or with zoledronic acid
followed by doxorubicin.
The treatment induced increase in programmed cell death was mirrored by a step-down in the cancer overconfident marker Ki-67.
There was no evidence of bone disease in whatever of the treatment groups as measured by microcomputed tomography and analysis of bone
histology.
The authors complete that:
"Sequential treatment with Dox [doxorubicin] followed by Zol [zoledronic acidulent] elicited substantial antitumor effects in hypodermic breast tumors in
vivo, in the absence of bone disease."
The researchers suggested that if these results are replicated in mankind in clinical settings, it could dramatically improve survival rates for thousands
of women currently having breast cancer intervention in the UK solitary.
Holen, wHO led the project, aforesaid that:
"Our work - exploitation a model system - has shown that treatment with the chemotherapy agent doxorubicin followed by zoledronic acid kills breast
tumours."
Holen explained that the results suggested that patients "may welfare the most if these two drugs are disposed in this particular order", and the team is
looking onward to "the results of a large breast cancer trial after this year to confirm our findings. This method of treatment could and so quickly be
incorporated into clinical practice."
Chief Executive of Breast Cancer Campaign, Pamela Goldberg, said:
"The results of this study are very encouraging and could change the way white meat cancer patients are tempered. The good news is the deuce treatments
victimised in this study are relatively inexpensive and already used in the clinic. Therefore we should promptly see the benefits giving women the best
possible chance of beating breast cancer."
Breast genus Cancer is the most vulgar cancer in the UK, where around 46,000 new cases are diagnosed every year.
"Antitumor Effects of Doxorubicin Followed by Zoledronic Acid in a Mouse Model of Breast Cancer.",
Penelope D. Ottewell , Hannu M�nkk�nen , Mark Jones , Diane V. Lefley , Robert E. Coleman , and Ingunn Holen
Journal of the National Cancer Institute, Advance Access published on August 11, 2008.
DOI 10.1093/jnci/djn240.
Click here for Abstract.
Sources: JNCI abstract, Sheffield University.
Written by: Catharine Paddock, PhD
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