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1.
J Cell Mol Med ; 26(2): 515-526, 2022 01.
Article in English | MEDLINE | ID: mdl-34921503

ABSTRACT

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.


Subject(s)
Pancreatic Neoplasms , Ribosomal Protein S6 Kinases, 70-kDa , Apoptosis , Cell Line, Tumor , Cell Proliferation , Deoxycytidine/analogs & derivatives , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/genetics , TOR Serine-Threonine Kinases/metabolism , Transcription Factors , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Gemcitabine
2.
Mol Med Rep ; 12(1): 119-26, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25738436

ABSTRACT

Estrogen receptors (ERs) are important for preventing endotoxin-induced myocardial dysfunction. Therefore, plant-derived phytoestrogens, which target ERs may also affect endotoxin-induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside-R1 (NG-R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG-R1 on cardiomyocytes and the precise cellular/molecular mechanisms underlying its action remain to be elucidated. In the present study, pretreatment with NG-R1 suppressed the lipopolysaccharide (LPS)-induced degradation of inhibitor of nuclear factor-κB (NF-κB) α, the activation of NF-κB and caspase-3, and the subsequent myocardial inflammatory and apoptotic responses in H9c2 cardiomyocytes. An increase in the mRNA and protein expression of ERα was also observed in the NG-R1-treated cardiomyocytes. However, the expression pattern of ERß remained unaltered. Furthermore, the cardioprotective properties of NG-R1 against LPS-induced apoptosis and the inflammatory response in cardiomyocytes were attenuated by ICI 182780, a non-selective ERα antagonist, and methyl-piperidino-pyrazole, a selective ERα antagonist. These findings suggested that NG-R1 reduced endotoxin-induced cardiomyocyte apoptosis and the inflammatory response via the activation of ERα. Therefore, NG-R1 exerted direct anti-inflammatory and anti-apoptotic effects on the cardiomyocytes, representing a potent agent for the treatment of myocardial inflammation during septic shock.


Subject(s)
Estrogen Receptor alpha/biosynthesis , Ginsenosides/administration & dosage , Inflammation/metabolism , Myocytes, Cardiac/drug effects , Shock, Septic/drug therapy , Animals , Apoptosis/drug effects , Endotoxins/toxicity , Estrogen Receptor alpha/metabolism , Gene Expression Regulation , Ginsenosides/chemistry , Humans , Inflammation/chemically induced , Inflammation/complications , Inflammation/pathology , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , NF-kappa B/biosynthesis , Panax notoginseng/chemistry , RNA, Messenger/biosynthesis , Rats , Shock, Septic/complications , Shock, Septic/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha
3.
Lab Med ; 46(1): 14-9, 2015.
Article in English | MEDLINE | ID: mdl-25617387

ABSTRACT

OBJECTIVE: To assess the diagnostic value of the T-SPOT.TB test in cases of breast turberculosis (BTB) in China. METHODS: We enrolled 13 female patients with primary BTB as the BTB test group and 10 healthy volunteers as the control group. The 2 groups underwent T-SPOT.TB tests and tuberculin skin tests (TSTs) before receiving a core-needle biopsy or excision biopsy. We then collected and analyzed T-SPOT.TB and TST data. RESULTS: The sensitivity of the T-SPOT.TB test for detection of BTB (84.6%) was significantly greater than that of TST (53.8%) (P <.05); the specificity of each test (80.0% and 60.0%, respectively) for BTB was not significantly different (P >.05). CONCLUSION: The T-SPOT.TB test could be a useful adjunct to current tests for diagnosis of BTB and could be used for early diagnosis of this condition.


Subject(s)
Breast/microbiology , Breast/pathology , Skin/pathology , Tuberculin Test , Tuberculosis/diagnosis , Adult , China , Epithelioid Cells/pathology , Female , Giant Cells, Langhans/pathology , Humans , Middle Aged , Skin/microbiology , Young Adult
4.
BMC Gastroenterol ; 14: 121, 2014 Jul 07.
Article in English | MEDLINE | ID: mdl-25002150

ABSTRACT

BACKGROUND: To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). METHODS: The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91). CONCLUSIONS: FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.


Subject(s)
Feces/chemistry , Inflammatory Bowel Diseases/diagnosis , Irritable Bowel Syndrome/diagnosis , Lactoferrin/analysis , Biomarkers/analysis , Diagnosis, Differential , Humans , Sensitivity and Specificity
5.
Invest New Drugs ; 28(6): 800-11, 2010 Dec.
Article in English | MEDLINE | ID: mdl-19789842

ABSTRACT

Previous study demonstrated that MONCPT, a topoisomerase I inhibitor, exhibited potent anti-proliferation and anti-angiogenesis activity in vitro and in vivo. In this study, we report the efficacy of MONCPT against the development of melanoma metastasis by an intravenous injection of green fluorescent protein-transfected mice melanoma carcinoma (B16F10-GFP) cells in C57BL/6 mice. MONCPT (2.0, 5.0 and 12.5 mg/kg/2 days) markedly decreased B16F10-GFP pulmonary metastases by 12.8%, 53.1% and 76.3%, respectively; whereas higher doses of MONCPT (31.0 mg/kg/2 days) significantly inhibited the tumor growth of B16F10 xenograft model. In the in vitro experiment, MONCPT suppressed the B16F10-GFP cell invasion and migration without affecting cell survival. Further studies demonstrated that MONCPT decreased the secretion of matrix metalloproteinase (MMP)-9 and VEGF, and reduced the protein expression of HIF-1α as well as the phosphorylation level of ERK in B16F10-GFP cells. These in vivo and in vitro results indicate that MONCPT possesses both the potent antimetastatic ability and the tumor growth-inhibition activity, and the dual function promises MONCPT as a potential therapeutic agent for tumor metastasis and tumor growth of melanoma carcinoma.


Subject(s)
Camptothecin/analogs & derivatives , Disease Models, Animal , Melanoma/drug therapy , Melanoma/pathology , Neoplasm Metastasis/drug therapy , Animals , Camptothecin/pharmacology , Camptothecin/therapeutic use , Cell Adhesion/drug effects , Cell Hypoxia/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Separation , Drug Screening Assays, Antitumor , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Green Fluorescent Proteins/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Melanoma/enzymology , Mice , Mice, Inbred C57BL , Neoplasm Invasiveness , Neoplasm Metastasis/pathology , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Transduction, Genetic , Vascular Endothelial Growth Factor A/metabolism
6.
Arch Pharm (Weinheim) ; 341(5): 273-80, 2008 May.
Article in English | MEDLINE | ID: mdl-18404777

ABSTRACT

A series of novel arylpyrrolylmaleimides was synthesized and evaluated for their in-vitro cytotoxicity against various human cancer cell lines and their protein-kinase C inhibitory activity. Some of the compounds showed high or moderate cytotoxic activity against the tested cell lines. Compound 6b is the most promising compound against the tested cancer cell lines; 6d and 6e showed moderate protein-kinase C inhibition. Structure-activity relationships are discussed based on the experimental data obtained.


Subject(s)
Antineoplastic Agents/chemical synthesis , Maleimides/chemical synthesis , Protein Kinase C/antagonists & inhibitors , Protein Kinase Inhibitors/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Maleimides/pharmacology , Protein Kinase Inhibitors/pharmacology
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