ObjectiveTo explore the mechanisms of perineural invasion (PNI) in pancreatic cancer so as to find a new treatment for pancreatic cancer. MethodsThe literatures on PNI, neurotropism, nerve-tumor microenvironment and nerve growth factor in pancreatic cancer were reviewed and the mechanisms of PNI were summarized. ResultsThe rich innervation of pancreatic tissue itself and the minute slits within perineural structure were the anatomic basis of PNI. Tumor cells expressed neural antigens were the pathological basis of PNI. Tumor-nerve microenvironment and nerve growth factor family and themselves receptors might play an important molecular role in PNI. However, tumor cells expressed neural antigens were not only closely related to the PNI, but also the interaction between tumor cells and nerves played an important role in PNI. ConclusionsThe detailed mechanisms of PNI are extremely complex and controversial up to today. However, it is possible to search a new therapeutic target in pancreatic cancer according to the mechanisms of PNI.
Objective The bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into insul in-producing cells (IPCs) in vitro. However, low differentiation efficiency and poor maturity are the main obstacles. To investigate the feasibil ity of BMSCs differentiation into IPCs in diabetic pancreatic microenvironment of pigs. Methods BMSCs were isolated and purified from the bone marrow of a 4-week-old male pig. Fifteen female pigs (aged 8 to 10 weeks, weighing 8 to 10 kg) were randomly divided into 3 groups: normal control group (group A, n=5), diabetic control group (group B, n=5), and BMSCs transplanted group (group C, n=5). The pigs of groups B and C were treated by auris vein injections of styeptozocin and alloxan for 3 days to induce diabetes mell itus (DM) model, whose blood glucose level 2 days all greater than 17 mmol/L was successful DM model. A total of 1.1 mL of the 3rd passage BMSCs labeled with enhanced green fluorescent protein (EGFP), with cell density of 5 × 107/ mL, were injected into subcapsular pancreas of group C at multi ple points, normal saline at the same dosage into those of groups A and B. After 30 days of monitoring blood glucose, the histological analysis of islet number and size were done; the immunofluorescence staining was used to detect the protein expression of insul in in the new-formed islets. The EGFP+ cells were collected from the sections using laser-capture microdissection; RT-PCR was used to detect insulin mRNA and pancreatic and duodenal homeobox factor 1 (PDX1) mRNA expressions from EGFP+ cells, and the insul in and sexdetermining region of the Y chromosome (SRY) genes were detected by fluorescence in situ hybridization (FISH). Results The blood glucose level decreased significantly in group C when compared with that in group B from 18 days and gradually decreased with time (P lt; 0.05). The histological observation showed that the number of islets was increased significantly in group C when compared with that in group B (10.9 ± 2.2 vs. 4.6 ± 1.4, P lt; 0.05), and there was no significant difference when compared with that in group A (10.9 ± 2.2 vs.12.6 ± 2.6, P gt; 0.05). The size of new-formed islets in group C was significantly smaller than that in group A [(47.2 ± 19.6) μm vs. (119.6 ± 27.7) μm, P lt; 0.05]. The immunofluorescence staining showed that new-formed islets of group C expressed insulin protein. RT-PCR showed that the microdissected EGFP+ cells of group C expressed insulin mRNA and PDX-1 mRNA. FISH showed that the new-formed islet cells of group C contained SRY gene in Y chromosome and insulin double positive cells. Conclusion BMSCs can differentiate into IPCs in diabetic pancreatic microenvironment of pigs.
Objective To review the research progress of osteoblasts in the hematopoietic microenvironment of bone marrow and regulatory pathways and mechanisms. Methods The advances in the osteoblasts as crucial components for hematopoietic microenvironment in bone marrow, regulation to osteoblasts and hematopoietic stem cells(HSCs), and correlative singal pathways and mechanisms were introduced based on the recent related literature. Results Evidence indicates that osteoblasts are crucial components of the hematopoietic microenvironments in adult bone marrow. The osteoblasts maintainthe quiescence of primitive HSCs by the signaling receptorsligands, secreted cell factors and celladhesion molecules and by regulating other cells in the niche. The quiescent primitive HSCs persist stem cell characteristic which has unlimited selfrenewal and multipotent differentiation potential. Conclusion The further understanding of the relationship between osteoblasts and hematopoietic microenvironment should lead to development of new strategies directed toward clinical therapeutics of HSCs transplantation.
Abstract To study the regulation of growth and proliferation of tissue-repair cell from wound microenvironment, the effects of wound fluid (WF) on the growth and proliferation of wound fibroblast were studied in vitro. Thirty rats were divided into 6 groups. On the back of every rat, an incision of 0.5～1.0cm was performed a subcutaneous sac was made by blunt dissection. A piece of sponge was put in, and the wound was sutured. After 1,3,7,9,11,15 days, one group of the rats were sacrificed respectively, and WF was collected from the sponge. Two kinds of medium were made with each WF: 1640+1%FCS+10%WF and1640+10%FCS+10%WF. After 48 hours incubation with newly prepared wound fibroblasts, the growth of the cells was observed. It was shown that (1) Under 1%FCS, WFfrom1,3,7 days stimulated cell proliferation, and WF from 9,11,15 days caused cell death. (2) Under 10%FCS, WF from 9,11,15 days inhibited cell growth. It was suggested that the wound microenvironment stimulated the fibroblasts to proliferate for one week after injury, and beyond that further growth seemed to be arrested, and that there might be some growth inhibitory factors present in the microenvironmentduring the late stage of wound healing.
【Abstract】Objective To give a summary of the current researches on hematopoietic stem cell niche. Methods Through extensive reviewing the related domestic and abroad literatures, the present summary reviews the components of hematopoietic stem cell niche, related cell factors and related cell signaling pathway participating in regulation of hematopoietic stem cell. Results The activities of hematopoietic stem cells are regulated by the niche (microenvironment), which is composed of hematopoietic stem cell and its surrounding cells. The regulation cannot be completed through one signaling pathway. Also, the self-renewal and differentiation of hematopoietic stem cell cannot be completed only through osteoblastic cells. Conclusion The niche regulates hematopoietic stem cells by different ways. With study in-depth, we will comprehensively understand the nature of stem cells and the study will provide a broader space to stem cell-based therapy.
ObjectiveTo review cancer associated fibroblasts(CAFs) and its role in the evolution of gastrointestinal neoplasms. MethodDomestic and international publications in relation to CAFs and its role in the evolution of gastrointestinal neoplasms were collected and reviewed. ResultsIn the gastrointestinal cancers, as the largest number and the most important stromal cells of the tumor microenvironment, CAFs induce the homeostasis of cell microenviron-ment out of balance, promote the remodeling of the tumor metabolism and extracellular matrix(ECM), and thus impulse the generation, proliferation, invasion and metastasis of the tumor by secreting different kinds of cytokines. ConclusionsThe key role CAFs playing in the tumor generation and evolution makes themselves and the multiple relatively specific molecules they secrete a new target for prognosis and targeted therapy, and this gives us a new idea for the combined treatment of gastrointestinal tumor or any other tumors.
ObjectiveTo review the research advances about myeloid derived suppressor cells(MDSC)and pancreatic cancer, and explore the future research trends. MethodRelated literatures in recent 5 years from abroad databases(PubMed, Web of Science, and EMBASE)and domestic databases(CNKI, WANFANG, and WEIPU)were collected and reviewed. ResultsThe MDSC was the core of tumor immune regulation network in pancreatic cancer microenvironment, it formed a complicated feedback with the pancreatic cancer and the stellate cells. MDSC could promote the cancerogensis and progression of pancreatic cancer, and the accumulation of MDSC in peripheral blood of pancreatic cancer patient could predict the poor prognosis. However up to now, the literatures about the relation between MDSC and the chemotherapy and metastasis of pancreatic cancer were limited. ConclusionsThe comprehensive therapy by targeting MDSC of pancreatic cancer is promising. However, many issues need to be further investigated.
ObjectiveTo summarize the regulating mechanism of microRNA in tumor microenvironment. MethodThe literatures about the studies on the mechanism regulated by microRNA for tumor microenvironment were reviewed according to the results searched from PubMed in recent years. ResultsmicroRNA might be participated in regulation of tumor microenvironment factors such as hypoxia-inducible factor, tumor associated fibroblasts, extracellular matrix, which leaded to a change in biological behavior of tumor cells by reforming the microenviroment. ConclusionsmicroRNA has been participated in regulating many factors of tumor microenvironment. The change of neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Therefore revealing microRNA mechanism for tumor microenvironment could not only help exploring the biological behavior of tumor cells, but also come an important insight for new means of diagnosis and treatment of cancer.