High expression of JMJD6 predicts unfavorable survival in lung adenocarcinoma.

The upregulated expression of JMJD6 was observed in various human cancers. However, little was known about JMJD6 expression and its clinicopathological significance in lung adenocarcinoma. The aim of this study was to investigate the expression and significance of JMJD6 in lung adenocarcinoma progression and prognosis. The levels of JMJD6 mRNA and protein in lung adenocarcinoma specimens and corresponding non-tumorous lung tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. In order to investigate the correlations between JMJD6 and the clinicopathological features of lung adenocarcinoma, the expression of JMJD6 in 154 patients with lung adenocarcinoma was detected by immunohistochemistry. By qRT-PCR and Western blot, the relative expression levels of JMJD6 mRNA and protein were significantly higher in lung adenocarcinoma tissues than in corresponding non-tumorous lung tissues (P < 0.001). Immunohistochemical staining revealed that high JMJD6 expression was closely correlated with tumor size (P = 0.005), pathological grade (P = 0.003), pT status (P = 0.012), pN status (P = 0.003), and pleural invasion (P < 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of JMJD6 resulted in a significantly poor prognosis of lung adenocarcinoma patients. Multivariate analysis showed that the status of JMJD6 expression was an independent prognostic factor for lung adenocarcinoma patients. Our results showed that JMJD6 plays a key role in lung adenocarcinoma and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in lung adenocarcinoma.

ADAM17 is overexpressed in non-small cell lung cancer and its expression correlates with poor patient survival.

The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P=0.026), tumor size (P=0.001), clinical stage (P=0.016), and lymph node metastases (P<0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.

Synthesis and biological evaluation of noscapine analogues as microtubule-interfering agents.

A series of noscapine analogues have been synthesized via 13-step reaction starting from 2-hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that ofnoscapine against HL-60 cell line and tubulin polymerization. Moreover, it induced a massive accumulation of cells in G2/M phase. These results showed noscapine and its derivatives were worth to be intensively studied further.

[Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities].

In order to find new indolin-2-one derivatives as antitumor agents, a series of 3-pyrrole substituted 1-(5-formyl-2-furanylmethyl) indolin-2-one derivatives were designed and synthesized. 5-Formyl-2 ,4-dimethyl-lH-pyrrole-3-carboxylic acid ethyl ester was condensed with 5-substituted indolin-2-one 2a-2d to afford 3-[(pyrrol-2-yl) -methylidenyl] indolin-2-ones 3a-3d. Through N-alkylation, 1-(5-formyl-furfuryl) -indolin-2-one 4a-4d were prepared. Compounds 4a-4d were then condensed with indolin-2-one to afford bis-indolin-2-one derivatives 5a-5d. The structures of the synthesized compounds were determined by 1H NMR, MS and element analysis. Antitumor activities of all the synthesized compounds in vitro were tested. All the 12 synthesized compounds possess antitumor activities against SPC-A1 strain. Especially the compounds 5a-5d possess potent antitumor activities better than sunitinib. Their IC50 are all below 5 micromol x L(-1).

[Synthesis of 1-indole substituted beta-carboline alkaloid and its derivatives and evaluation of their preliminary antitumor activities].

AIM: To synthesize eudistomin U and its 6-OCH3/Br derivatives and 5'-Br derivatives as antitumor agents. METHODS: Using tryptamine and indole-3-aldehyde as starting materials, through condensation, Pictet-Spengler cyclization and dehydrogenation three steps, the alkaloids and its derivatives were prepared. RESULTS: The structures of the compounds were determined by 1HNMR, MS and HRMS. Antitumor activity in vitro was tested. CONCLUSION: Eudistomin U and its derivatives were synthesized. The results showed that they all showed antitumor activities against mouse P388 strain.

Anticarcinogenic and antioxidant activity of diindolylmethane derivatives.

AIM: To investigate the synthesis methods and the bioactivity of diindolylmethane (DIM) derivatives. METHODS: 1) A 3D-Quantitative Structure-Active Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) study of 14 DIM derivatives was investigated to predict their anticarcinogenic activity. 2) Based on CoMFA model, a series of new derivatives of DIM were designed and synthesized. 3) Their free radical scavenging and antioxidant potentials were tested using in-vitro DPPH radical scavenging and ?-carotene antioxidant models. 4) The anticarcinogenic activities of some compounds were tested by using microculture tetrazolium assay (MTT) and sulforhodamine B (SRB) proteochromosomic assays. RESULTS: 1) The CoMFA model derived from DIM analogues proved a good predictive ability with q2 value of 0.827. 2) New designed compounds 3c and 4c exhibited 3-fold more potent radical scavenging activity than reference substance Vitamin E in DPPH model expressed by IC50 values. 3) The primary antitumor screening essay showed that some DIM derivatives designed exhibited the inhibitory activities to some tumor cell growth at relatively high concentration, and DIM was the most effective among them. CONCLUSION: DIM's 3D-QSAR model is reliable. According to it, eleven DIM derivatives were synthesized, and two derivatives of them possess potent radical scavenging activities and some showed the inhibitory activities in primary anticancer assay in vitro.