Abstract: Tumor associated macrophages (TAMs) perform various task that are essential for tumor growth, angiogenesis, metastasis, and tumor invasion. Growth factors, chemokines, cytokines and the extra cellular matrix in the tumor microenvironments signal the TAMs to perform these tasks. The tumor microenvironment is not homogeneous and can be classified into several distinct regions such as sites of tumor invasion, perivascular, hypoxic and stromal regions. Each of these sites likely has different cytokines and signaling molecules in their microenvironment that might signal and direct the function of TAMs. The purpose of this project is to isolate and analyze TAMs from distinct tumor regions to gain a better understanding of the mechanism behind the specialized role of these TAMs. As a first step towards this goal, micro array analysis was conducted on flow sorted TAMs and developmental macrophages expressing yellow fluorescence protein (YFP). Micro array data from age matched developmental macrophages was compared to TAMS from early, premalignant stage of breast cancer, and late stage metastatic breast cancer to find the genes which were upregulated in TAMs versus developmental macrophages, and in late stage TAMs versus TAMs from the earlier premalignant stage of breast cancer. From this list of genes upregulated in TAMs, candidate cell surface macrophage markers that could be used to classify TAMs based on there association with one of the distinct tumor microenvironments was selected. These candidate markers will be used to visualize macrophages associated with different regions within the tumor microenvironment using immuno-staining of tumor sections. In preliminary work, CD16 was selected as one potential candidate gene that was upregulated late in tumor development compared to earlier stages. Immunostaining indicated CD16 was expressed on a set of macrophages near blood vessels near the tumors, but not in macrophages located within tumors. Further evaluation of these markers would facilitate isolation of different subsets of macrophages within tumor and understanding the function of these macrophages in tumor microenvironment. Another major cell group involved in all the changes in the tumor microenvironment discussed is the fibroblast. Originally the fibroblast inhibits the growth of the tumor. However through natural selection tumors evolve to change the microenvironment and like wise the function the fibroblast are performing to aid in tumor progression rather than suppress tumor progression. These fibroblast reprogrammed by the tumor cells are called tumor associated fibroblast TAFs. TAFs aid in tumor progression by angiogenesis, immune suppression, and matrix remodeling, providing growth and anti apoptotic factors and aid in metastasis by recruiting TAMs. A key gene involved with this is IKK. It is our hypothesis that ablating IKK in the fibroblast will lead to a reduction of tumor growth.

Today, the arsenal of “high-precision” or “targeted” radiotherapy includes a variety of techniques and approaches that, like the pieces of a puzzle, need to be put together to provide the prostate cancer patient with high-level optimized radiation treatment. This book examines in detail the role of these innovative radiation techniques in the management of prostate cancer. In addition, a variety of current controversies regarding treatment are carefully explored, including whether prophylactic treatment of the pelvic lymphatics is essential, the magnitude of the effect of dose escalation, whether a benefit accrues from hypofractionation, and what evidence exists for the superiority of protons or heavy ions. Radiotherapy in Prostate Cancer: Innovative Techniques and Current Controversies is intended for both radiation oncologists and urologists with an interest in the up-to-date capabilities of modern radiation oncology for the treatment of prostate cancer.

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

As the number of patients with colitis-associated cancer (CAC) is on the increase, the purpose of this book is to review the latest topics concerning management of the disease. In recent years, the diagnostic power of endoscopy and molecular pathology has also grown tremendously, as a result of which they now have a far greater influence on the treatment of CAC. At the moment, appropriate monitoring programs for ulcerative colitis and Crohn’s disease remain uncertain. At the same time, the latest findings on DNA methylation and microRNAs hold the promise of making revolutionary changes in these areas. Moreover, recent drug advances in the treatment of inflammatory bowel diseases have changed surgical indications. On the other hand, the indication of mucosectomy on colorectal cancer in ulcerative colitis and prophylactic abdominoperineal resection for Crohn’s disease remain controversial. This book provides the latest information on the remaining issues of CAC from the point of view of expert surgeons.

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.