Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.Experimental Design: The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues.Results: MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer.Conclusions: Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets.
Gold nanoshells functionalized with a small peptide as a targeting agent were designed and synthesized for photothermal therapy of hepatocarcinoma. The nanoshells exhibited high absorption in the near-infrared (NIR) range, 800-1,100 nm, and were functionalized with 12-amino acid sequence peptides for targeting liver cancer cells. The nanoshells were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscope (TEM) and IR spectra. The functionalized gold nanoshells showed good targeting ability to liver cancer cells BEL-7404 and BEL-7402 while not to the normal healthy liver cell HL-7702, and also had a low cytotoxic activity. The fluorescence images showed that the gold nanoshells caused death to the liver cancer cells efficiently after being treated with a NIR light in vitro. These simple, stable, low cytotoxic, cancer-cell targeting gold nanoshells present a great promise as delivery agents for the selective photothermal treatment of liver cancer cells.
The chiral Rh(I)-diene-catalyzed asymmetric three-component reaction of aryldiazoacetates, aromatic amines, and β-nitroacrylates was achieved to obtain γ-nitro-α-amino-succinates in good yields and with high diastereo- and enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of Rh(I)-associated ammonium ylides by nitroacrylates. This new transformation represents the first example of Rh(I)-carbene-induced ylide transformation.
An enantioselective four-component reaction of a diazoketone, water, an aniline and ethyl glyoxylate in the presence of catalytic Rh2(OAc)4 and a chiral Brønsted acid was developed to efficiently produce β-hydroxy-α-amino acid derivatives in good yields with high diastereoselectivity and enantioselectivity.
Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that 'smart' gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The 'smart' gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia.
<p>Ribosomes produce most proteins of living cells in seconds.
Here we report highly efficient chemistry matched with an automated fast-flow
instrument for the direct manufacturing of peptide chains up to 164 amino acids
over 328 consecutive reactions. The machine is rapid - the peptide chain
elongation is complete in hours. We demonstrate the utility of this approach by
the chemical synthesis of nine different protein chains that represent enzymes,
structural units, and regulatory factors. After purification and folding, the
synthetic materials display biophysical and enzymatic properties comparable to
the biologically expressed proteins. High-fidelity automated flow chemistry is
an alternative for producing single-domain proteins without the ribosome.<i></i></p>
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