**7. References**


These conflicting reports might indicate that there seem to be other factors determining the relationship between MCD and tumor progression. The conflicting results may also depend on wide variations in timing, tumor types/stages, methodologies, and the chemotherapy application as well. Importantly, some studies are not able to reflect the direct effects of MCs on tumor biology because many patients receive adjuvant chemotherapy in the time of sampling. So, some of the effects can be accounted for by the therapeutic response to chemotherapy. Nonetheless, by only observing increased MCD in and around a tumor, making a correlation between good or bad prognosis and specimens seems inadequate to

Development of this method was initiated by the author in Wayne State University in Detroit, MI and later completed during his tenure at Louisiana State University—HSC, New Orleans, LA in USA. The author thanks to Liqiao Ma for editing English in the chapter.

Prior, C. & Sesenna, R. (1953). Mast cells and their relation to the tumors of the bladder. *Rivista di Anatomia Patologica e di Oncologia*, Vol.7, No.8, pp. 809- 838. Henderson, W.R.; Chi, E.Y.; Jong, E.C. & Klebanoff, S.J. (1981). Mast cell-mediated tumor-

Ghiara, P.; Boraschi, D.; Villa, L.; Scapigliati, G.; Taddei C. &Tagliabue A. (1985). In vitro

Richards, A.L.; Okuno, T.; Takagaki, Y. & Djeu, J.Y. (1988). Natural cytotoxic cell-specific

Marshall, J.S. & Jawdat, D.M. (2004). Mast cells in innate immunity. *The Journal of Allergy and Clinical Immunology*, Vol.114, No.1, (2004 July), pp. 21-27. ISSN: 0091-6749 Özdemir, Ö. (2007). Evaluation of human mast cell-mediated cytotoxicity by DIOC18 target

Özdemir, Ö. (2011). Flow cytometric mast cell-mediated cytotoxicity assay: a three-color

Della Rovere, F.; Granata, A.; Monaco, M. & Basile G. (2009). Phagocytosis of cancer cells by

Leskinen, M.J.; Lindstedt, K.A.; Wang, Y. & Kovanen, P.T. (2003). Mast cell chymase induces

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explain their real role.

**6. Acknowledgment** 

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**7. References** 


**2**

**The Application of** 

*United States of America* 

**Membrane Vesicles for Cancer Therapy** 

Valenzuela Malyn May A., Park Joon S., Turay David and Wall Nathan R.

Cancer, a leading cause of death globally, is projected to become more prevalent in coming years due to increasing life expectancy. Among possible treatment options, the use of biomarkers especially has shown great potential as a gateway to personalized medicine, and in turn, great promise for improved diagnosis, prognosis and treatment of cancer and other diseases. However, the use of biomarkers in cancer therapeutics has thus far exhibited mild success, at best. The most common tool used for biomarker discovery is plasma proteomics due to the accessibility of blood samples and the rapid development of highly sensitive proteomics technologies. However, other body fluids such as urine may also be a reservoir

Extracellular membrane vesicles ranging in diameter of 30-1000 nm and originating from various cellular origins have been increasingly recognized for their participation in a variety of both normal and pathological cellular processes. Regardless of their cell type of origin these membrane bound vesicles or exosomes provide a protected and controlled internal microenvironment outside the cell for metabolic objectives of the host cell to be carried out at a distance from the host cell. They are also believed to be instrumental in cell-cell and cellextracellular communication. Moreover, while knowledge of exosome biogenesis and physiological relevance remains limited, accumulating evidence suggests that their bioactivity may be clinically applicable in cancer therapeutics. One recent work suggests that the use of exosomes in immunotherapy may prime the immune system to recognize and kill cancer cells and thus could form a viable basis for the development of novel cancer

This chapter will review current knowledge pertaining to exosomes, describe possible uses of exosomes in immunotherapy, and address challenges and future directions in bringing

Since their description in the process of reticulocyte maturation almost a quarter century ago (Johnstone *et al.*, 1987), exosomes; the intralumenal vesicles (ILV's) of multivesicular bodies (MVB's), have gained significant notoriety as evidenced by the nearly 10-15 fold rise in the

exosome-based cancer vaccines or immunotherapies closer to clinical reality.

**2. Exosome biogenesis, secretion and physiologic considerations** 

**1. Introduction**

vaccines.

for important marker proteins.

Khan Salma, Jutzy Jessica M.S., Aspe Jonathan R.,

*Ctr. for Health Disparities & Mol. Med.Loma Linda, California,* 

*Loma Linda University, Dept. of Biochemistry,* 

