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ABSTRACT: Objective To investigate the role of the cell cycle-related novel gene CDK2-associated, culin clomain 1(CACUL1) in tumor cell apopotosis and explore the relationship between CACUL1 and apoptosis regulation. Methods We induced the cell cycle arrest by ultraviolet radiation and chemotherapeutic drugs and then studied the expression of CACUL1 in cell DNA damage state. Meanwhile, Western blotting, Northern blotting and other methods were applied to detect the expression of the CACUL1 at both protein and mRNA levels and analyze their relationships with p53 in p53 wild-type and knock-out colorectal cancer cells. Results The CACUL1 was proved related to the regulation of apoptosis. In the case of DNA damage induced by ultraviolet radiation and chemotherapeutic drugs, the expression of CACUL1 protein peaked at 2 h, and with time went by, the expression of CACUL1 gradually decreased. The increase of CACUL1 expression was independent of p53. Northern blotting revealed that the increased expression of CACUL1 was post-transcriptional regulation. It was also found that the high expression of CACUL1 inhibited cell apoptosis induced by ultraviolet radiation and chemotherapeutic drugs. Conclusion The role of CACUL1 in cell apoptosis is to help cells cross the G1/S checkpoints in a posttranscriptional regulation of p53-independent manner, thus facilitating cell survival.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 05/2013; 29(5):462-4.
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ABSTRACT: Bone metastasis of gastric cancer is relatively uncommon in clinical practice. Moreover, it is all the more unusual for the primary presentation of gastric malignancy to be bone metastasis. Here, we describe a male patient who complained of pain and edema in his right lower extremity. Further assessment by computed tomography and positron emission tomography revealed an abnormally thickened gastric cardia and a giant neoplasm in the right pelvis with bone damage. Consequently, the finding of adenocarcinoma cells in pelvic and cardia biopsy specimens contributed to the diagnosis of pelvic metastasis from gastric cancer. This case report illustrates that stomach cancer has the potential, although far less than breast, prostate and lung cancers, to metastasize to bone. In addition, it highlights the peculiarity of this bone metastasis which is pelvic, solitary and huge.
Journal of biomedical research. 07/2012; 26(4):303-6.
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ABSTRACT: The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m(2) in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.
Journal of biomedical research. 05/2012; 26(3):159-64.
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ABSTRACT: Sorafenib is a multi-target oral anticancer drug used as first-line treatment for patients with advanced human hepatocellular carcinoma (HCC). But the exact mechanism of sorafenib involved in HCC treatment is not clear yet. In this study, a comparative proteomic approach was performed to identify novel sorafenib-related proteins in HCC. Proteomes of HepG2 cells treated with sorafenib and the control (without sorafenib) were obtained by two-dimensional differential gel electrophoresis. Comprehensive analysis of proteins was focused on total protein spots to filtrate the different protein spots between the two groups. The differentially expressed proteins were identified by peptide mass fingerprinting with high-performance liquid chromatography-tandem mass spectrometry. Then, Western blot and immunohistochemistry were used to verify the expression of some candidate proteins. Results indicated that 19 protein spots were differentially expressed with significant changes, including 6 up-regulated proteins and 13 down-regulated proteins. It was confirmed by Western blot that expressions of Annexin A1 and cyclophilin A were down-regulated in sorafenib-treated HCC cell lines. Immunohistochemical study revealed their oncogenic role in HCC tissues. These observations might be novel findings leading to bring new insights into the exact mechanism of sorafenib and identify possible therapeutic targets.
Medical Oncology 07/2011; 29(3):1827-36. · 2.14 Impact Factor
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ABSTRACT: Aim: To investigate the unbalance of proliferation and apoptosis and the functions of cell-cycle proteins and apoptotic factor in metastasis of hepatocellular carcinoma (HCC) and their effect in prognosis.Methods: Proliferation index and apoptosis index, as well as seven relatively molecular markers, namely p15, p34, p53, p57, p73, survivin and nm23, were evaluated by immunohistochemistry and TUNEL in HCC tissues and compared to adjacent non-cancerous tissues and normal liver tissues. Furthermore, the prognostic significance by follow-up and mutual relationships for each clinicopathologic factor and molecular marker were analysed.Results: The dysregulation between proliferation and apoptosis and the abnormal expression of seven molecular markers were observed in HCC tissues. The unbalance of proliferation and apoptosis and abnormal expressions of p15, p34, p57 and nm23 were correlated with TNM stage and extrahepatic metastasis. In particular, the abnormal co-expression of nm23/p57 correlated with advanced TNM stage and bigger tumor size and was an independent prognostic factor of HCC.Conclusion: The unbalance of proliferation and apoptosis and abnormal expression of cell-cycle proteins promote metastasis of HCC. Moreover, the abnormal co-expression of nm23/p57 may be a useful molecular marker for metastasis and unfavourable prognosis for HCC.
Hepatology Research 09/2010; 40(11):1107 - 1116. · 2.20 Impact Factor
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ABSTRACT: p57 is a cyclin-dependent kinase (CDK) inhibitor, the first cell cycle regulator that is regulated by imprinting. p57 was initially considered to be a tumor suppressor based on its ability to regulate cell cycle progression through its N-terminal domain. Now, it has been found that p57 is also involved in the regulation of other cellular processes including transcription, apoptosis, differentiation, development, and migration via its PAPA repeat and carboxyl-terminal domain. The multifunction of p57 participate in many processes in tumorigenesis involving in different mechanisms including loss of imprinting, loss of heterozygosity, promoter methylation, histone deacetylation and regulation of microRNAs. Moreover, upstream signaling pathways, protein-protein interactions and altered subcellular localization have also been reported to participate in abnormal expression of p57 resulting in the occurrence and progression of cancer. However, it is unclear whether p57 may play a dual role during tumorigenesis under different cellular processes similarly to its siblings. The presence of a nuclear localization signal in p57 is intriguing because it may affect the subcellular localization of p57, which can result in abnormal proliferation and motility of cells, and may be oncogenic under certain circumstances, as observed for p21 and p27.
International Journal of Oncology 06/2010; 36(6):1321-9. · 2.40 Impact Factor
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ABSTRACT: Pancreatic cancer is generally refractory to most chemotherapeutic agents. We investigated whether hSSTR2 expression and octreotide treatment reverse multidrug resistance of human pancreatic cancer cells. We used pancreatic cancer cells that were transfected by using a lentivirus expression system, which allowed stable expression of the hSSTR2 gene in the pancreatic cancer cells. BxPC-3 cells were transfected with hSSTR2 through a lentivirus vector pWP XL-MOD-SSTR2 in order to enable the expression of hSSTR2. The transfected cells were treated with different concentrations of octreotide and with the chemotherapeutic agents cisplatin, epirubicin, fluorouracil and gemcitabine. The changes in IC50 following treatment with chemotherapeutic agents were determined, and the expression of different MDR indicating marker genes, multidrug resistance gene-1 (MDR1), multidrug resistance-associated protein 2 (MRP2), and lung resistance-related protein (LRP), were evaluated. Octreotide treatment of the transfected cells significantly decreased the IC50 of chemotherapeutic agents in a dose-dependent manner. hSSTR2 gene transfection decreased MDR1, MRP2 and LRP expression by 57, 47 and 56%, respectively (P<0.01), and octreotide treatment (1.6 microg/ml) for 48 h, decreased it further by 88, 73 and 87<, respectively (P<0.01). These data suggested that the down-regulation of MDR genes is responsible for the improvement in the chemotherapeutic sensitivity of hSSTR2-expressing pancreatic cancer cells, when these cells are subjected to octreotide treatment.
Oncology Reports 12/2009; 22(6):1391-6. · 1.84 Impact Factor
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ABSTRACT: Cell cycle progression is tightly controlled by cyclins and cyclin-dependent kinases (CDKs). CDK2 plays a crucial role in regulating cell cycle progression, but how CDK2 is regulated is still incompletely understood. In this study, we report the identification and characterization of a novel gene CAC1 that regulates CDK2 activity. The open reading frame sequence of this gene encodes a protein of 369 amino acids which contains a Cullin domain, and this protein is physically associated with CDK2. As such, we have designated it Cdk-Associated Cullin1, or CAC1. CAC1 is highly expressed in cancer tissues and cancer cell lines. Interestingly, CAC1 is expressed in a cell cycle-dependent manner and its expression is high in late G(1) to S phase. Knockdown of CAC1 by RNAi inhibits cell proliferation and induces G(1)/S arrest. Since CAC1 interacts with CDK2 and promotes the kinase activity of CDK2 protein, we propose that CAC1 is a novel cell cycle associated protein capable of promoting cell proliferation. Our data provide insight into the mechanism by which CDK2 is regulated and the molecular basis of cell cycle progression in cancer.
Cell cycle (Georgetown, Tex.) 11/2009; 8(21):3544-53. · 5.36 Impact Factor
