Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration.

Transcription factors, human E26 transcription factor 1 (Ets1) and specific protein 1 (Sp1), are known to induce gene expression in tumorigenicity. High Ets1 expression is often associated with colorectal tumorigenesis. In this study, we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression. The interaction domains are further addressed to be the segment at Sp1(626-708) and the segment at Ets1(244-331). In addition, the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration. Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells. Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

Case report: First case of pemetrexed plus cisplatin-induced immune hemolytic anemia in a patient with lung adenocarcinoma.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening drug-related complication. There are no previous reports of pemetrexed plus cisplatin as first-line chemotherapy for non-small cell lung cancer, resulting in DIIHA. Case presentation: In this report, a patient with advanced-stage lung adenocarcinoma developed severe immune hemolytic anemia 21 days after pemetrexed plus cisplatin chemotherapy. Laboratory findings showed severe hemolysis, including a rapid decrease in hemoglobin (HGB) and an elevated level of reticulocytes (Rets), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). A workup for the possibility of DIIHA was performed, including a direct antiglobulin test (DAT), a test in the presence of the soluble drug, and a drug-treated red blood cell (RBC) test. It showed a strongly positive (3+) result for anti-C3d but not for anti-immunoglobin G (IgG) in DAT. Enzyme-treated RBCs reacted weakly with the patient's serum and pemetrexed when complement was added. In addition, the patient's serum and normal sera were reactive with cisplatin-treated RBCs. However, eluates from the patient's RBCs and diluted normal sera were non-reactive with cisplatin-coated RBCs. Untreated and enzyme-treated RBCs reacted with the patient's serum in the presence of soluble cisplatin. In vitro serological tests suggested that complement-dependent pemetrexed antibodies and cisplatin-associated non-immunologic protein adsorption (NIPA) might combine to cause immune hemolytic anemia. The patient's anemia gradually recovered when pemetrexed and cisplatin were discontinued. Conclusion: This rare case demonstrated that complement-dependent pemetrexed antibodies and cisplatin-associated NIPA might occur simultaneously in a patient with DIIHA.

Identification of NOVA family proteins as novel ß-catenin RNA-binding proteins that promote epithelial-mesenchymal transition.

The NOVA (neuro-oncological ventral antigen) protein family, composed of two paralogs, NOVA1 and NOVA2, consists of RNA-binding proteins involving in processes such as alternative splicing and transport of some target mRNAs. The function of NOVA has been well studied, and increasing evidence has shown that NOVA proteins may be important contributors to carcinogenesis. However, the molecular mechanisms underlying the roles of NOVA proteins in carcinogenesis remain to be determined. Here, we have identified both NOVA1 and NOVA2 as novel ß-catenin RNA-binding proteins. The NOVA1/NOVA2 heterodimer positively regulates ß-catenin expression by enhancing ß-catenin mRNA stability. Furthermore, we demonstrated that NOVA1 and NOVA2 promote epithelial-mesenchymal transition via ß-catenin in breast cancer cells, as NOVA-induced upregulation of epithelial and mesenchymal marker expression was attenuated by restoring ß-catenin expression. Our results advance the current understanding of ß-catenin post-transcriptional regulation and shed light on the role of NOVA proteins in cancer, suggesting that NOVA proteins are potential therapeutic targets in breast cancer.

[Differences in shapes and properties and microscopic frameworks of wild and cultivated Radix Salviae Miltiorrhizae from different regions].

OBJECTIVE: To compare the differences in shapes and properties and the microscopic frameworks of the wild and cultivated Radix Salviae Miltiorrhizae from different regions. METHOD: The differences in the shapes and properties, the characters of transverse sections, the powder and disintegrated tissue of roots were compared using microscopic measurement and statistics analysis. RESULT: The wild Radix Salviae Miltiorrhizae had several long cylinder roots with rough flaky squama skin and brown red or wine culour, the cultivated had root of many branch with cling skin and brick-red or chestnut culour. The difference of microscopic histological structure was that the xylem vessel of wild Radix Salviae Miltiorrhizae had bunched vessel with the rank form of big diameter alternating with small diameter, and had stone cell on samples from some producing region, the xylem vessel of the cultivated had no bunched vessel and no stone cell with the rank form of tangential radial. Radix Salviae Miltiorrhizae cultivated in Sichuan Province is called original-region medicinal materials and named Chuandanshen. Chuandanshen had the differences with the Salviae Miltiorrhizae Radix cultivated in other region. The root of Chuandanshen had 1.2 cm diameter, and was bulky and fat with solid fabric and the fracture with brownish yellow color and cutin-alikeness, its xylem vessel of transverse section of root was thin with the rank form of tangential radial, and 19-24 vascular bundle and a few wood fiber. CONCLUSION: Salviae Miltiorrhizae Radix of the wild and the cultivated, of the original-region (Chuandanshen) and the other-region, have the differences in the shapes and properties, and the microscopic frameworks. The character can be identified by the differences in the shapes of medicinal materials, and the rank form of vascular bundle of transverse section of root.

[A new method to obtain molecular marker of sequence-tagged site (STS) of Panax ginseng and P. quinquefolius].

OBJECTIVE: Searching a new molecular method to authenticate Panax ginseng and P. quenquefolium. METHOD: Single primers based on rDNA sequences of Panax species were designed to obtain polymorphic bands of P. ginseng and P. quinquefolius and then sequenced. Four PCR primers (two forword and two reverse primers) specific to P. ginseng and P. quinquefolius were designed. RESULT: Primer Pg-6F, Pg-479R only amplified 474 bp band for P. ginseng and primer Pq-442F, Pq-658R only amplified 217 bp band for P. quinquefolius. It is indicated that the four primers could serve as specific STS primers for Panax species. CONCLUSION: A new way to obtain STS primers of Panax species was established. This method is more quick and efficient than SCAR-PCR method and can serve as a model to obtain molecular markers for other Chinese material medica.

[A new molecular identification method: anchored primer amplification polymorphism DNA].

To build up a stable and easy doing method for molecular identification in traditional Chinese medicine, on basis of RAPD, the new method mainly changed the primer length and PCR annealing temperature. Panax ginseng, Panax quinquefolius and its nine adulterants were used to establish the method and test it using MARMS primers published in 2004. The new method also used to authenticate Chinese Materia Medica of Tian-hua-fen (Radix Trichosanthes) and Bai-zhi (Radix Angelica). Primer Pg-q36F obtained polymorphic bands of P. Ginseng, P. quinquefolius and its adulterants. The identification result is identical to that published before and more stable. Primer TkS1-64F obtained polymorphic bands of Tian-hua-fen and its nine adulterants. Primer AfS1-100F obtained polymorphic bands of Bai-zhi and its three adulterants. The method has good stability and reproducibility and can easily identify authertic medicines from their adulterants. It was a potential molecular method to identify other Chinese Materia Medica. The method was named as anchored primer amplification polymorphism DNA (APAPD).

[Determination of flavone for Scutellaria baicalensis from different areas by HPLC].

OBJECTIVE: To describe the difference between native and nonative herbs by determining contents of seven kinds of flavone for twenty-five samples from seventeen areas. METHODS: HPLC. Fluid phase: MEOH-H2O-CH3COOH(ICE) (41:59:0.2) and (50:50:0.2). Detection wavelength: 275. RESULTS: The contents of baicalin are 6%-9%, wogenin are 2%-8%, baicalein are 0.1%-1.6%, neobaicalein are 0.01%-0.2%, wogonin are 0.01%-0.3%, visidulin and oroxylin are trace amounts or undetected. CONCLUSION: The native and nonative herbs have no distinct differce in absolute component ratio. The ratio of baicalin and wogenin is under three. The ratio of baicalin and baicalein, baicalin and wogonin is between twenty and fifty.