Give and Take

[Tom]

I thought this was fascinating. Then again, I find almost all medical research fascinating, so you might not be as easily impressed...lol. Now I need to find out what chemotherapy agents are vascular disrupting agents. It also reminds me that there is seldom a free lunch when treating cancers, but sometimes there is a hidden dessert in the bag after all.
Tom


Drug therapy induces recruitment of endothelial progenitor cells to tumors

Reuters Health
Posting Date: September 21, 2006

Last Updated: 2006-09-21 14:00:18 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment of tumors with vascular disrupting agents causes circulating endothelial progenitor cells (CEPs) to home in on and promote the survival of the targeted tumor, findings from an animal study indicate.

The good news is that treatment with antiangiogenic agents can disrupt CEP recruitment, thereby improving the efficacy of the vascular disrupting agent, according to the report in the September 22nd issue of Science.

"These results reinforce our hypothesis that CEPs mobilized from the bone marrow are a major contributor to the growth of the viable tumor rim after treatment with vascular disrupting agents," senior author Dr. Robert S. Kerbel, from Sunnybrook Health Sciences Centre in Toronto, and colleagues note.

Whether bone marrow-derived CEPs play a role in tumor angiogenesis is controversial, the authors note, primarily because so few of these cells are typically present in the blood vessels of untreated tumors. The findings of Dr. Kerbel's group, however, indicate that treatment changes this, as CEPs mobilize and travel to the tumor.

The viable tumor rim and tumor blood flow could be markedly reduced by disrupting the CEP spike through the use of antiangiogenic agents or by genetic manipulation, the report indicates.

The results "provide a mechanistic rationale for the enhanced efficacy of vascular disrupting agents when combined with antiangiogenic drugs," the researchers conclude.

Science 2006;313:1785-1787.

[Joy]

I think many of us find these postings interesting and vital to our sense of hope-thank you so much. Plus you always crack me up!

[Lani]

Thanks--I looked at the original article and they tried two VDAs (vascular disrupting agents) both of which had long abreviations and numbers and were not clinically available chemotherapies.

I found the following last few sentences, paragraph which might put people thinking "counterintuitively" as they said:

"Together, these results reinforce our hypothesis that CEPs mobilized from the bone marrow are a major contributor to the growth of the viable tumor rim after treatment with VDAs.

Our results illustrate that although CEP levels in vessels of untreated tumors are typically low, these levels can suddenly rise in response to acute stress, such as that caused by treatment with a VDA and possibly with other treatments such as maximum-tolerated-dose cytotoxic chemotherapy (17). This situation may be analogous to the rapid reactive mobilization and homing of CEPs to damaged vessels or arteries that occurs after pathological cardiovascular events such as myocardial infarcts (18). Our results also provide an additional mechanistic rationale for the enhanced efficacy of VDAs when combined with an antiangiogenic drug (9). Finally, they suggest that when a VDA is to be combined with chemotherapy, consideration should be given to the counterintuitive idea of administering chemotherapy shortly after VDA treatment, rather than the opposite sequence, because of the ability of chemotherapy to target CEPs (17, 19)."

[heblaj01]

An other process taking place when antiangiogenesis drugs are used may influence the activities of VDA's. I am refering to research (mainly by Dr R. Jain) showing that in the initial phase of the mode of action of antiangiogenesis drugs some new capillaries are damaged but others feeding tumours are "repaired" making them less leaky & temporarily reducing the internal pressure in tumours. This decrease allows a "window of opportunity" for anticancer drugs to more easily penetrate the tumours.