ABSTRACT
Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.
Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Fructose-Bisphosphate Aldolase/metabolism , Co-Repressor Proteins/metabolism , Transcription Factors/genetics , Kidney Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: The pathological changes of osteoarthritis are similar to that of kaschin-beck disease, but the cause of the latter is still unclear,damage is more serious. From the comparison of pathology changes between them, we hope to find out an effective therapeutic method with the assistance of arthroscope basing on the experiences in osteoarthritis.OBJECTIVE: To make comparison of the histomorphological changes between osteoarthritis and kaschin-beck disease with knee arthroscope,which give clues to the diagnosis and selection of operative technique for kaschin-bock disease under arthroscope.DESIGN: Case control study.SETTING: Department of Orthopaedics, Shaanxi People's Hospital.PARTICIPANTS: Thirty-five patients who needed arthroscope surgery due to severer knee osteoarthritis were randomly selected from Department of Orthopaedics, Shaanxi People's Hospital between April 1998 and September 2000; Meanwhile 31 patients with knee joint functional obstacle caused by kaschin-beck disease (epidemic disease area) were randomly selected from Luochuan Hospital of Shaanxi Province in November 2001.METHODS: Japanese made OLYMPUS series color television arthroscope and surgery system were used to carry out knee joint operations in all participants. During the operation, video recording, postoperative editing, photographs, comparison and analysis were conducted, in order to find out the pathological changes of the two groups in knee joint synovium, patella, femur, tibia and meniscus with the assistance of arthroscope.RESULTS: Totally 66 patients were enrolled in this study and all endamage in Kaschin-beck disease and osteoarthritis: Injuries were graded into grade 0, 1, 2 and 3, there were 0,3,5,23 cases and 0,3,16,16cases correspondingly in kaschin-beck disease group and osteoarthritis cartilage damage was presented by big piece of cartilage peeled off, part of them came off leading to bone exposure, the exposed bone surface is uneven; while cartilage damage in osteoarthritis was presented by the wear of cartilage, moreover cartilage island was found remained in the exposed bone with the surface covered with fiber strips and the exposed observed in 24 patients with Kaschin-beck disease, 5 cases with coarse stress point and 19 cases with burr-like damage, amongst which there were 9 cases displayed both medial and lateral meniscus damages; in osteoarthritis group there were 16 cases showed meniscus damages including edge wears in11 cases and breakage in 5 cases.CONCLUSION: Cartilage damage in knee articular was obviously severer in Kaschin-beck disease than in osteoarthritis, although kaschin-beck disease is no matter resulting in serious knee joint damage, but its pathology changes are different from osteoarthritis, we should pay more attention to the peculiarity of big piece of cartilage peeling off during operations.
ABSTRACT
Objective To investigate the epidemiological status of visceral leishmaniasis in Hamangou coal mine area of Korla City of Xinjiang Uygur Autonomous Region.Methods Based on a hint of possible existence of patients, a retrospective survey was carried out house by house to find cases with suspected signs/symptoms of the disease.Meanwhile, a survey on current status was conducted, including physical examination(liver and spleen palpation) to those less than 15 years-old, leishmanin skin test and rk39 immunochromatographic strip test for part of the residents.Bone marrow smears were examined for the cases with clinical signs/symptoms and positive rk39 strip test.Sandflies were collected using routine methods in and around the area, identified, and dissected to find infection of promastigotes.Results Leishmanin skin test was performed in 185 people with a positive rate of 21.1%(39/185), 39 out of 140 local residents who have lived there for more than 6 years showed positive(27.9%) , while all residents who have lived less than 6 years and children under 5 years old were negative.Of the 81 children under 15 years old with a negative skin test, one showed positive for rk39 strip test, and leishmania body was found in the bone marrow smear of this case, so confirmed as visceral leishmaniasis.12 sandfies were identified as Phlebotomus alexandri, and natural infection with promastigotes was found in one sandly.Conclusion The investigation confirms that visceral leishmaniasis is endemic in the Hamangou coal mine area.