Background: Our previous studies of human breast and prostate cancer have shown that aberrant immune cell infiltration is associated with focal tumor capsule disruption and tumor cell budding that facilitate invasion and metastasis. Our current study attempted to determine whether aberrant immune cell infiltration would have similar impact on colorectal cancer (CRC).Materials and Methods: Tissue sections from 100 patients with primary CRC were assessed for the frequencies of focal basement membrane (BM) disruption, muscularis mucosa (MM) fragmentation, and tumor cell dissemination in epithelial structures adjacent and distal to infiltrating lymphoid aggregates using a panel of biomarkers and quantitative digital imaging.Results: Our study revealed: (1) epithelial structures adjacent to lymphoid follicles or aggregates had a significantly higher (p<0.001) frequency of focally disrupted BM, dissociated epithelial cells in the stroma, disseminated epithelial cells within lymphatic ducts or blood vessels, and fragmented MM than their distal counterparts, (2) a majority of dissociated epithelial cells within the stroma or vascular structures were immediately subjacent to or physically associated with infiltrating immune cells, (3) the junctions of pre-invasive and invasive lesions were almost exclusively located at sites adjacent to lymphoid follicles or aggregates, (4) infiltrating immune cells were preferentially associated with epithelial capsules that show distinct degenerative alterations, and (5) infiltrating immune cells appeared to facilitate tumor stem cell proliferation, budding, and dissemination.Conclusions: Aberrant immune cell infiltration may have the same destructive impact on the capsule of all epithelium-derived tumors. This, in turn, may selectively favor the proliferation of tumor stem or progenitor cells overlying these focal disruptions. These proliferating epithelial tumor cells subsequently disseminate from the focal disruption leading to tumor invasion and metastasis.
Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer.
Tissue engineering is a promising approach to regenerate transplantable tissue or organ substitutes in vitro. However, the existing methods are based on seeding cells on macroscale polymer scaffolds, which are associated with several challenges including limited control over cell microenvironment, limited nutrient diffusion, directed cell alignment. The emerging bottom-up tissue engineering methods hold great potential to address these challenges by assembling building blocks into complex 3D tissue constructs. In this study, we developed a layer-by-layer assembly approach to recreate 3D cell-laden constructs. Our experiment showed the predefined channels form a vascular system and help the transplant cells to transport the requirement of culture cells in early case of cells attaching and growing up. It is an original concept to demonstrate the feasibility of forming a network with a vascular geometry in a biocompatible polymer and fabricated different scaffold with different cells. The concept was developed to create a complete branching vascular circulation in 3D on surface of mixture of chitosan and gelatin structures and pre-define the structure of channel for culturing smooth muscle for controlling the SMC growing up as smooth muscle fiber.
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