anment that promotes angiogenesis, tumor survival and me tastasis. Targeting regulatory T cells has been of great interest to potentially remove the suppression of ef fecter T cells and enhance tumor specific immune response. Depletion LY2228820 of regulatory T cells using an ti CD25 monoclonal antibodies or regulatory T cell inhibiting agents, such as cyclophosphamide, has been shown to have anti tumor effects in preclinical models. In addition, MDSC suppress the cytokine production as well as the cytotoxic capacity of natural killer cells, playing a critical role in the host defense against cancer, in HCC patients. Impaired NK cells can affect anti tumor immune re sponses, which contributes further to tumor escape from both innate and adaptive immune responses in patients with HCC.
Anti multiple drug resistance Survival Calcium Channel of stem like cells in response to chemotherapeutic drugs is thought to be governed by the presence of active transmembrane adenosine tri phosphate binding cassette transporter family members, such as MDR1, ABCG2 and ABCC2. It is believed that stem like SP cells, which are known for their ability to efflux the DNA binding dye Hoechst 33342, confer resistance to chemotherapeutic drugs, including cisplatin and doxorubicin, through expression high levels of such ABC transporters. In SP cells purified from HCC cell lines, inhibi tion of MDR1, ABCG2 and ABCC2 reverses their chemoresistance. These cells have been shown to harbor other CSC like properties, and may be related to the metastatic potential and chemoresistance of HCC.
Moreover, it was demonstrated that ex pression of granulin epithelin precursor and ABCB5 in liver CSCs is associated with chemo resistance and reduced survival times of patients with HCC. Anti Radioresistance Several experimental and clinical findings pro vide evidence that the number of CSCs in a cancer affects its radiocurability. Recurrent tumors after ra diotherapy could originate from one surviving CSC, and a permanent local tumor control requires inacti vation of all CSCs. Tumor cell hypoxia and tu mor cell repopulation are the main factors causing radioresistance. Oxygen mediates the majority of the biological effects of sparsely ionizing radiation, and the response of cells to radiation depends strongly on the availability of oxygen. Various methods to deliver oxygen to cancer tissue have been studied.
Enhanced tumor oxygenation has previously been achieved in an animal model using the synthetic heme based ox ygen carrier, albumin heme which is a recombinant human serum albumin Fe cyclohexanoil heme. The rHSAFeP is a candidate radia tion enhancing drug, and arterial infusion of rHSA FeP may serve as a local oxygeneation method that enhances the radiation effect. Future Directions The rapid development of the CSC field, com bined with genome wide screening techniques, has allowed for the identification of important new CSC markers and pathways, and these discoveries have contributed to one of the most important deve