Browsing by Subject "Colon"
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Item Does patient rurality predict quality colon cancer care? a population based study(2013-06) Chow, Christopher J.Introduction: Over fifty million people reside in rural America. However, the impact of patient rurality on colon cancer care has been incompletely characterized. We hypothesize that patient rurality impacts colon cancer care quality measures. Methods:Using the 1996-2008 California Cancer Registry, we identified 123,129 patients with stage 0-IV colon cancer. Baseline characteristics were compared by rurality status. Controlling for covariates, multivariate regression models were used to examine the impact of rurality on stage, adequate lymphadenectomy and receipt of chemotherapy. Cox proportional hazards was used to examine cancer specific survival. Results: Of our cohort, 18,735 (15%) resided in rural areas. Rural residence was associated with white or American Indian race. Controlling for covariates, our multivariate models demonstrate that rurality was associated with later stage of diagnosis, inadequate lymphadenectomy and inadequate receipt of chemotherapy. In addition, rurality was associated with worse cancer specific survival. Conclusions: A significant proportion of patients treated for colon cancer live in rural areas. Yet, rural residence is associated with later stage, poor adherence to quality measures and poorer survival. Future quality improvement measures should target rural patients to ensure both that structure of care is optimal and that appropriate processes of care are followed.Item Regulation of Anti-Tumor Immunity and Immunotherapy Response In Colorectal Cancer(2020-06) Zhao, XiandaImmune checkpoint blockade therapy (ICBT) has revolutionized the treatment and management of numerous cancers, yet a substantial proportion of colorectal cancer (CRC) patients are resistant. Most importantly, the mechanisms that cause ICBT resistance in CRC patients are mostly unclear. Both clinical and laboratory studies implied that both tumor cell-intrinsic factors and traditional cancer therapies (e.g., chemotherapy and oncogenic pathway-targeted therapy) have regulatory effects on anti-tumor immunity and ICBT efficacy. In the present thesis, we first characterized the pathological and immunological features of different pre-clinical CRC models. We reported the feasibility of using small animal endoscopy to establish mouse orthotopic colon tumors. We found that tumors grown orthotopically in the colon microenvironment develop better immune infiltration than tumors with the same genetic background growing in a subcutaneous microenvironment. These data indicated that the tissue microenvironment impacts anti-tumor immunity. Meanwhile, we observed that the endoscopy-guided cancer cell line-originated orthotopic CRC model is much more sensitive to ICBT over the subcutaneous model, making it not suitable for experiments that require ICBT-resistant tumors. This observation made us decide to use the subcutaneous tumor models, which are ICBT-resistant, for understanding cancer immunotherapy resistance. In the second section, we evaluated the impact of tumor-draining lymph nodes (TdLNs) and chemotherapy on ICBT efficacy. Specifically, we demonstrated TdLNs are critical for tumor antigen-specific T-cell response in early-stage tumors. However, TdLNs shift from an immunoreactive to an immunotolerant environment during tumor development. In mice with advanced primary tumors, TdLNs are not the major reservoir of tumor antigen-specific T cells. To evaluate the impacts of those immunotolerant TdLNs on ICBT response, we established a surgical model to mimic tumor recurrence in situ. We surgically removed the established primary tumors with or without concurrent TdLNs resection. Then, we inoculated secondary tumors, which are in the same lymphatic drainage area as the primary tumors, to mimic tumor recurrency. Notably, removing those immunotolerant TdLNs concurrently with established primary tumors did not affect the ICBT response on localized secondary tumors. In another set of experiments, we evaluated the impacts of chemotherapy (5-FU) on ICBT efficacy. We revealed that using 5-FU as induction treatment for ICBT increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T-cell depletion. However, sustained chemotherapy impaired the efficacy of ICBT by suppressing the host immune system and depleting tumor-infiltrating T cells. Therefore, the sequential combination of chemotherapy with ICBT may result in a better response than the sustained chemotherapy and ICBT combination. Finally, we investigated how tumor cells regulate T-cell activation via intercellular communication based on extracellular vesicles (EVs). Specifically, we revealed that tumor cells-secreted EVs (TEVs) containing microRNA miR-424 suppressed the CD28-CD80/86 costimulatory pathway in tumor-infiltrating T cells and dendritic cells. Modified TEVs with miR-424 knocked down enhanced T-cell mediated antitumor immune response in CRC tumor models and increased the response to ICBT. Intravenous injection of modified TEVs induced tumor antigen-specific immune responses. Moreover, injections of modified TEVs boosted the ICBT efficacy in CRC models that mimic treatment-refractory late-stage disease. Collectively, the present study improves our understanding of CRC anti-tumor immune regulation and proposed novel treatment for ICBT resistant human CRC.Item A simple test to check for colorectal cancer.(2012-07-24) Eklund, Derek