ABSTRACT
Plant innate immunity depends in part on recognition of pathogen-associated molecular patterns (PAMPs), such as bacterial flagellin, EF-Tu, and fungal chitin. Recognition is mediated by pattern-recognition receptors (PRRs) and results in PAMP-triggered immunity. EF-Tu and flagellin, and the derived peptides elf18 and flg22, are recognized in Arabidopsis by the leucine-rich repeat receptor kinases (LRR-RK), EFR and FLS2, respectively. To gain insights into the molecular mechanisms underlying PTI, we investigated EFR-mediated PTI using genetics. A forward-genetic screen for Arabidopsis elf18-insensitive (elfin) mutants revealed multiple alleles of calreticulin3 (CRT3), UDP-glucose glycoprotein glucosyl transferase (UGGT), and an HDEL receptor family member (ERD2b), potentially involved in endoplasmic reticulum quality control (ER-QC). Strikingly, FLS2-mediated responses were not impaired in crt3, uggt, and erd2b null mutants, revealing that the identified mutations are specific to EFR. A crt3 null mutant did not accumulate EFR protein, suggesting that EFR is a substrate for CRT3. Interestingly, Erd2b did not accumulate CRT3 protein, although they accumulate wild-type levels of other ER proteins. ERD2B seems therefore to be a specific HDEL receptor for CRT3 that allows its retro-translocation from the Golgi to the ER. These data reveal a previously unsuspected role of a specific subset of ER-QC machinery components for PRR accumulation in plant innate immunity.
Subject(s)
Arabidopsis Proteins/immunology , Arabidopsis/immunology , Endoplasmic Reticulum/immunology , Host-Pathogen Interactions/immunology , Immunity, Innate/physiology , Alleles , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Arabidopsis Proteins/physiology , Base Sequence , Calreticulin/genetics , Calreticulin/immunology , Calreticulin/physiology , DNA Primers/genetics , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/physiology , Genes, Plant , Glucosyltransferases/genetics , Glucosyltransferases/immunology , Glucosyltransferases/physiology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/physiology , Immunity, Innate/genetics , Membrane Proteins/genetics , Membrane Proteins/immunology , Membrane Proteins/physiology , Mutation , Plant Diseases/immunology , Plant Diseases/microbiology , Plants, Genetically Modified , Protein Kinases/genetics , Protein Kinases/immunology , Protein Kinases/physiology , Pseudomonas syringae/immunology , Pseudomonas syringae/pathogenicity , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Endostatin and SU6668 combined with 5-FU on the growth and metastasis of human colon cancer in vivo and its mechanism.</p><p><b>METHODS</b>Metastatic model of human colon cancer was established by orthotopic implantation of human tumor tissue into colon wall of nude mice. Twelve days later, mice were randomly divided into saline water control, Endostatin, SU6668, Endostatin plus SU6668, and Endostatin plus SU6668 and 5-FU groups, intraperitoneal injected respectively every day for four weeks. Six weeks after implication, the tumor weight, inhibition rates, intratumoral microvessel density (MVD) and metastasis were evaluated after the mice were sacrificed.</p><p><b>RESULTS</b>Compared with the control, tumor growth was significantly inhibited in mice treated respectively with Endostatin, SU6668, Endostatin plus SU6668 and Endostatin plus SU6668 and 5-FU with an inhibition rate of 0, 64.9%, 63.5%, 76.4% and 88.2% respectively,and MVD decreased significantly in treated groups [(18.10+/-5.65) vs (2.75+/-0.75), (3.17+/-0.58), (0.94+/-0.42) and (0.36+/-0.45)]. The incidences of peritoneal and region lymph node metastases were significantly inhibited in Endostatin, SU6668, Endostatin plus SU6668 and Endostatin plus SU6668 and 5-FU (90% vs 16.7%, 25%, 0 and 0; 90% vs 0, 0, 0 and 0). The growth and metastasis of human colon cancer implanted in nude mice were significantly inhibited in Endostatin, SU6668, Endostatin plus SU6668, and Endostatin plus SU6668 and 5-FU, and the effect of Endostatin plus SU6668 and 5-FU was the most obviously.</p><p><b>CONCLUSION</b>Endostatin plus SU6668 and 5-FU has strong inhibitory effect both on tumor growth and metastasis of human colon cancer.</p>
Subject(s)
Animals , Humans , Male , Mice , Angiogenesis Inhibitors , Therapeutic Uses , Cell Line, Tumor , Colonic Neoplasms , Drug Therapy , Pathology , Endostatins , Therapeutic Uses , Fluorouracil , Therapeutic Uses , Indoles , Therapeutic Uses , Lymphatic Metastasis , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic , Pyrroles , Therapeutic UsesABSTRACT
Objective: To investigate the clinical features of metastatic carcinoma of bone marrow. Methods: A total of forty-one cases with metastatic carcinoma of bone marrow were collected. The clinical manifestations including symptoms, laboratory examination and imaging diagnosis were observed and analyzed. Results: The most common symptoms were bone pain, fever, and weight loss. Anemia, thrombocytopenia and the presence of immature erythrocytes and leukocytes in peripheral blood were common hematological abnormalities. Serum alkaline phosphatase levels were increased in 68% of patients. The emission computed tomography (ECT) examinations showed lesions in the bone in 88% of patients. Nineteen patients (46%) had carcinomas of unknown origin, thirteen patients had lung cancer, three patients had prostate cancer and six patients had other primary malignancies. Eighteen patients received chemotherapy. The median survival time of the forty-one patients was only 3.6 months. However, a lung cancer patient had stable disease for 13 months after chemotherapy. Conclusion: When one or more of the following features are present: bone pain, fever, weight loss, hematological abnormalities, an increase in serum alkaline phosphates and bone lesions on ECT, metastatic carcinoma of bone marrow should be considered. To verify this diagnosis, bone marrow aspiration is a simple and valuable method. Chemotherapy as early as possible may slow down the progress of disease.