Convergent synthesis of functionalized derivatives of stage-specific embryonic antigens 3 & 4.

Stage-specific embryonic antigens (SSEAs) are carbohydrate markers that have diverse roles in embryonic development. However, the exact roles of SSEAs remain unclear. To obtain mechanistic insights into their roles, we aimed to develop functionalized SSEA glycan analogs via chemical synthesis.

Transcription of DNA duplex containing deoxypseudouridine and deoxypseudoisocytidine, and inhibition of transcription by triplex forming oligonucleotide that recognizes the modified duplex.

We developed new DNA triplexes that contain four base triads T-A·T, A-ψ·C, G-PIC·Y, and C-G·Py+, where C, Y, Py, ψ, and PIC are 5-bromocytosine, 5-methyl-4-pyrimidone, 2-aminopyridine, the aglycons of deoxypseudouridine, and deoxypseudoisocytidine, respectively. DNA duplex incorporating T-A, A-ψ, G-PIC, and C-G, and triplex forming oligonucleotide incorporating T, C, Y, and Py formed the triplex as evaluated by measurements. The triplex formation was successfully applied to the inhibition of transcription of the DNA duplex incorporating T7-promoter sequence modified by the above modified bases.

Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer.

Background: The expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is related significantly to the overall survival of patients with various cancers. RCAS1 reportedly induces apoptotic cell death in peripheral lymphocytes, which may contribute to the escape of tumor cells from immune surveillance. RCAS1 expression also has been related to tumor invasiveness and size in uterine cervical cancer.

Repeated exposures to daytime bright light increase nocturnal melatonin rise and maintain circadian phase in young subjects under fixed sleep schedule.

Effects of two different light intensities during daytime were examined on human circadian rhythms in plasma melatonin, core body temperature, and wrist activity under a fixed sleep schedule. Sleep qualities as indicated by polysomnography and subjective sleepiness were also measured. In the first week, under dim light conditions ( approximately 10 lx), the onset and peak of nocturnal melatonin rise were significantly delayed, whereas the end of melatonin rise was not changed.

Maternal deprivation in neonatal rats of different conditions affects growth rate, circadian clock, and stress responsiveness differentially.

Effects of periodic maternal deprivation (MD) were examined in rat pups on growth rate, circadian phase and period at weaning, and stress responsiveness in adulthood. MD was performed from postnatal day 1 to day 6 or day 7, with or without keeping ambient temperature at 37 degrees C and humidity at 70-80% during deprivation. Times of day and length of MD were also changed.

Maternal deprivation in neonatal rats alters the expression of circadian system under light-dark cycles and restricted daily feeding in adulthood.

Effects of maternal deprivation (MD) with different conditions were examined on the circadian rhythms in plasma corticosterone and locomotor activity in adult rats under ad libitum and restricted daily feeding (RF), in which rats had free access to food for 2 h for 3 weeks. Three different types of MD were performed from postnatal day 1 (P1) to day 6 (P6); MD for 12 h/day (MD12), for 3 h/day in the morning (MD3am) and in the afternoon (MD3pm). Under ad libitum feeding, corticosterone levels at 08:00 h and 24:00 h were significantly increased in MD12 rats.

Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer.

Purpose: Lysophosphatidic acid, which is enriched in the peritoneal fluid of ovarian cancer patients, plays a key role in the progression of ovarian cancer. Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases. We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphatidic acid-induced pathogenesis of ovarian cancer.

Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy.

Ovarian cancer is the most frequent cause of cancer death among all gynecologic cancers. We demonstrate here that lysophosphatidic acid (LPA)-induced ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF) is a critical to tumor formation in ovarian cancer. We found that among the epidermal growth factor receptor (EGFR) family of growth factors, HB-EGF gene expression in cancerous tissues and HB-EGF protein levels in patients' ascites fluid were significantly elevated.

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities.

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated form (HBdeltatm) of the molecule. HB(uc/uc) mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice.

The stress- and inflammatory cytokine-induced ectodomain shedding of heparin-binding epidermal growth factor-like growth factor is mediated by p38 MAPK, distinct from the 12-O-tetradecanoylphorbol-13-acetate- and lysophosphatidic acid-induced signaling cascades.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a critical growth factor for a number of physiological and pathological processes. HB-EGF is synthesized as a membrane-anchored form (pro-HB-EGF), and pro-HB-EGF is cleaved at the cell surface to yield soluble HB-EGF by a mechanism called "ectodomain shedding." We show here that the ectodomain shedding of pro-HB-EGF in Vero cells is induced by various stress-inducing stimuli, including UV light, osmotic pressure, hyperoxidation, and translation inhibitors.