Metastasis Volume

AP23451 administration to mice inoculated with MDA-231 breast cancer cells effectively prevents metastasis-induced osteolysis similar to bisphosphonate zoledronic (Zometa ). However, it also significantly reduces the volirme of tumor cells inside the bone marrow cavities of the mice as opposed to a lack of inhibitory effect on tirmor cell volume in mice treated with zoledronic acid. AP23588 is also a bone-targeted Src kinase inhibitor which has been determined to possess both anti-resorptive and anabohc properties in vitro with respect to reducing osteoclast activity and stimulating osteoblast activity, respectively. 

No. of Animals Tumor volume (mm3) Mean S.E. Lung metastasis (no. of colonies) Mean S.E... 

An orthotopic model of mCRC with a high rate of metastasis to the para-aortic lymph nodes has been developed utilizing implantation of tumor cells into the submucosal layer of the rectum (11, 12). In these models, primary tumor burden is evaluated by measuring tumor volume with a caliper, while lymph node metastasis is evaluated histologically. 

On the contrary, they are extremely useful because in vitro studies minimize or eliminate variables that complicate interpretation, contribute to interexperimental variability, and cloud model development. Other chapters in this volume will focus on the proper use of and interpretation of in vitro assays of adhesion, invasion, etc. The focus of this chapter will be on the methodologies used to study metastasis in vivo. Parallel studies utilizing both in vivo and in vitro approaches are powerful strategies for dissecting the biochemical and molecular basis for cancer metastasis. 

The most critical component for the study of metastasis is metastasizing cells. Since most people obtain their cells from cell culture, it is important to outline some of the criteria for the proper preparation and maintenance of those cultures. Details are omitted regarding verification of species of origin (karyotype, isozyme expression, etc.), tissue of origin (surface markers, enzyme expression patterns) and absence of opportunistic infections. It is presumed that such characterization will be done by readers of this volume before any... 

The mechanics for experimental metastasis assays are similar to those for the spontaneous metastasis assay. As above, volume and viscosity of the inoculum are important parameters. Volumes should never exceed 0.2 ml because plasma blood volume exceeds the normal range ( 10%) such that the distribution pattern of cells is altered. Tumor density is even more critical for intravascular injections since introduction of emboli can cause death because of vascular obstruction. Therefore, the same concentration maximums reported above are also applicable for this type of assay. 

The relationships between immune functions of the host and metastasis as a function of stress have been examined in mice bearing Lewis lung carcinoma subjected to rotational stress. Since some immune parameters were shown to display rhythmic variations, the occurrence of seasonal factors has been also taken into consideration. Indeed, the increase in metastasis number and volume caused by rotational stress varied in magnitude with a highly significant circannual rhythm, the acrophase coinciding with summer solstice. 

Table IS. Effects of 50% ethanol extract and ethyl acetate-soluble fraction of Angelica keiskei roots on tumor volume and lung metastasis in LLObearing mice...

Animal No. Tumor volume (mm ) Lung metastasis (No. of colonics)... 

As shown in Table (16) , Fr. 1 and Fr. 2at a dose of 100 mg/kg, twice daily significantly inhibited tumor volume and tumor weight on day 15. Furthermore, the above two fractions inhibited metastasis to the lung and the increase of lung weight that occurred in tumor-removed mice Table (16) . 

Table 16. ElTecIs of fractions 1 and 2 derived from ethyl acetate fraction of A. heiskei root on tumor volume and tnmor weight in LlX -bearing mice, and on long weight and tumor metastasis to lung in dead and snrviving carcinectomized LLC-bearing mice...

Also, hCG is useful in identifying patients with trophoblastic tumors and, together with AFP, in detecting non-seminomatous testicular tumors. Levels of hCG correlate with the tumor volume and disease prognosis. The presence of hCG in seminoma may indicate the presence of choriocarcinoma. Because hCG does not cross the blood-brain barrier, the normal cerebrospinal fluid-to-serum ratio is 1 60. Higher levels in cerebrospinal fluid may indicate metastases to the brain. Furthermore, the response to therapy for patients with central nervous system metastasis may be indicated by monitoring the hCG level. 

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