Aqueous Solutions of a Porous Host-Poly-L-lysine Complex with Information on Solids as Different Fluorescence by Guests.

N,N'-Dipyrid-3-yl-1,4,5,8-naphthalenediimide linked to two tris(pentafluorophenyl)borane (1) exhibits strong fluorescence emission in the solid state by the formation of a charge-transfer complex containing small aromatic guest molecules. Hydrophobic 1 was dissolved in water by mixing with poly-L-lysine (PLL) as a solubilizing agent. The 1-PLL complex could include small aromatic guest molecules in water, significantly increasing the fluorescence. The fluorescence maxima of 1 in aqueous solution and solid state were different depending on the guest molecule. Therefore, compound 1 was prepared as aqueous solution with information of fluorescence on solids by complexation with PLL.

Room-Temperature Phosphorescence Emitters Exhibiting Red to Near-Infrared Emission Derived from Intermolecular Charge-Transfer Triplet States of Naphthalenediimide-Halobenzoate Triad Molecules.

Invited for the cover of this issue is Toshikazu Ono, Yoshio Hisaeda and co-workers at Kyushu University and their collaborators at Ochanomizu University, Chuo University, and Institute for Molecular Science. The image depicts a molecular assembly structure shining like a jewel, glowing in the red-to-near infrared region. Read the full text of the article at 10.1002/chem.202100906.

Room-Temperature Phosphorescence Emitters Exhibiting Red to Near-Infrared Emission Derived from Intermolecular Charge-Transfer Triplet States of Naphthalenediimide-Halobenzoate Triad Molecules.

Room-temperature phosphorescence (RTP) emitters have attracted significant attention. However, purely organic RTP emitters in red to near-infrared region have not been properly investigated. In this study, a series of naphthalenediimide-halobenzoate-linked molecules are synthesized, one of which exhibits efficient RTP properties, showing red to near-infrared emission in solid and aqueous dispersion. Spectroscopic studies and single-crystal X-ray diffraction analysis have shown that the difference in the stacking modes of compounds affects the optical properties, and the formation of intermolecular charge-transfer complexes of naphthalenediimide-halobenzoate moiety results in a bathochromic shift of absorption and RTP properties. The time-dependent density functional theory calculations showed that the formation of charge-transfer triplet states and the external heavy atom effect of the halogen atom enhance the intersystem crossing between excited singlet and triplet states.

Downregulation of EphA7 by hypermethylation in colorectal cancer.

A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription-polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P=0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 downregulation in colorectal cancer, we examined the methylation status of the 5'CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P=0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P=0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P=0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5'CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.

EPHA2/EFNA1 expression in human gastric cancer.

The erythropoietin-producing hepatocellular (EPH)A2 receptor, tyrosine kinase, is overexpressed and phosphorylated in several types of human tumors and has been associated with malignant transformation. A recent report, however, indicated that stimulation of the EPHA2 receptor ligand, ephrinA1 (EFNA1), inhibits the growth of EPHA2-expressing breast cancer. The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue. EPHA2 was more highly expressed in tumor tissue than in normal tissue in 27 cases (55%). EFNA1 was overexpressed in tumor tissue in 28 cases (57%). No significant correlation was detected between the expression levels and histologic features such as tumor size, age, vessel invasion, or lymph node involvement. However, EPHA2 overexpression was more prominent in macroscopic type 3 and 4 tumors than in type 1 or 2 advanced gastric cancer. The authors observed EPHA2 expression in three of the four gastric cancer cell lines (AGS, KATO3, and MKN74) that were examined. In one cell line, TMK1, EPHA2 expression was barely detectable using northern blotting, RT-PCR, and western blotting. In contrast, EFNA1 was detected in all cell lines. In the gastric cancer cell lines that endogenously expressed EPHA2, stimulation with ephrinA1-Fc led to decreased EPHA2 protein expression and increased EPHA2 phosphorylation. Finally, the growth of EPHA2-expressing cells was inhibited by repetitive stimulation with soluble ephrinA1-Fc. Taken together, these findings suggest that EPHA2 and EFNA1 expression may influence the behavior of human gastric cancer.

Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer.

Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi-quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double-staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P = 0.100 for EPHA2 and P = 0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P = 0.007]. Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P = 0.001]. Tumors less than 5 cm in diameter and in stages I and II were significantly more likely to overexpress EPHA2 and EFNA1 (P = 0.001 for EPHA2, P = 0.001 for EFNA1). Microvessel counts (MVCs) after immunostaining for CD34 were significantly correlated (r = 0.343, P = 0.037) with overexpression of EPHA2. EPHA2-expressing focal cancer also surrounded microvessels in adenomas with focal cancers. These findings suggest an involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel induction.

Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer.

PURPOSE: We have previously reported that EPHB2 is overexpressed in gastric cancer; however, the expression profiles of its ligands, EFNB1 and EFNB2, are unknown. This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer. METHODS: Semi-quantitative RT-PCR using (32)P was performed on human gastric cancer tissues and corresponding normal tissues (29 gastric cancer patients). RESULTS: EPHB2 was more highly expressed in tumor tissues than in normal tissues in 21 out of 29 (72.4%), in gastric cancer patients ( P = 0.01); EFNB1 and EFNB2 were highly expressed in 21 out of 29 (72.4%) ( P = 0.037) and 14 out of 29 (48.3%) patients, respectively. The overexpression of EPHB2 was frequently detected in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma [10/13 (76.9%) and 9/14 (64.3%), respectively]. On the other hand, the overexpression of EFNB1 was more frequently detected in poorly differentiated adenocarcinoma than in well-differentiated adenocarcinoma [12/14 (85.7%) and 7/13 (53.8%), respectively. P =0.027]. Elevated levels of EPHB2 and EFNB1 were detected in substantial subsets of early gastric cancers. Genomic alterations to these three genes in gastric cancer specimens were either not found or rarely found except for several rare variations of EPHB2. CONCLUSIONS: These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer.