Carbohydrate-based block copolymer systems: directed self-assembly for nanolithography applications.

Self-assembly of block copolymers (BCPs) provides an attractive nanolithography approach, which looks especially promising for fabrication of regular structures with characteristic sizes below 10 nm. Nevertheless, directed self-assembly (DSA) and pattern transfer for BCPs with such small features remain to be a challenge. Here we demonstrate DSA of the maltoheptaose-block-polystyrene (MH1,2k-b-PS4,5k) BCP system using graphoepitaxy. BCP thin films were self-organized by solvent vapor annealing in tetrahydrofuran (THF) and water into sub-10 nm scale cylinders of the maltoheptaose (MH) block oriented horizontally or perpendicularly to the surface in a polystyrene (PS) matrix. The guiding patterns for graphoepitaxy were made by the electron beam lithography (EBL) and lift-off process with the distance gradually varying between 0 and 200 nm. Atomic force microscopy (AFM) investigation of MH1,2k-b-PS4,5k BCP DSA patterns revealed good ordering of vertical and horizontal cylindrical MH arrays for DSA lines with 150-200 nm separation. Reactive ion etching (RIE) of MH1,2k and PS4,5k thin films in O2 and CF4 plasma showed up to 14 times higher etch rate of MH compared to PS. These results indicate that MH1,2k-b-PS4,5k is a promising BCP for nanolithographic applications below 10 nm.

Self-assembly of maltoheptaose-b-PMMA block copolymer systems: 10nm Resolution in thin film and bulk states.

This paper describes the self-assembly of oligosaccharide-based hybrid block copolymers (BCPs) consisting of maltoheptaose (MH) and poly(methyl methacrylate) (PMMA) into 10nm scale lamellar and cylindrical phases depending on the volume fractions of MH (ϕMH) and the annealing process. Time resolved SAXS study of the BCP bulk samples during thermal annealing indicated that the BCPs phase separate into 10nm scale periodical structures. The solvent vapor annealing induced self-organizations of the BCP into different phases depending on ϕMH and the weight fraction of THF/H2O. BCPs with relatively higher ØMH, MH-b-PMMA3k (ϕMH=0.27) and MH-b-PMMA5k (ϕMH=0.16) self-organized into lamellar phases while the BCP sample with relatively lower ϕMH, MH-b-PMMA9k (ϕMH=0.10), self-organized into cylindrical phase by using THF/H2O=1/4 (w/w). On the other hand, the solvent vapor annealing with larger fraction of THF, i.e. THF/H2O=2/3 (w/w), induced cylindrical phases for MH-b-PMMA3k and MH-b-PMMA5k.

VPA alleviates neurological deficits and restores gene expression in a mouse model of Rett syndrome.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder that occurs once in every 10,000-15,000 live female births. Despite intensive research, no effective cure is yet available. Valproic acid (VPA) has been used widely to treat mood disorder, epilepsy, and a growing number of other disorders. In limited clinical studies, VPA has also been used to control seizure in RTT patients with promising albeit somewhat unclear efficacy. In this study we tested the effect of VPA on the neurological symptoms of RTT and discovered that short-term VPA treatment during the symptomatic period could reduce neurological symptoms in RTT mice. We found that VPA restores the expression of a subset of genes in RTT mouse brains, and these genes clustered in neurological disease and developmental disorder networks. Our data suggest that VPA could be used as a drug to alleviate RTT symptoms.

Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex.

Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. It is well known that dynamic epigenomic regulation (including chromatin remodeling and histone modifications by transcriptional coregulator complexes) is involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell type and developing stage-specific activity is largely unknown. In this study we aimed to isolate the histone demethylase lysine-specific demethylase 1 (LSD1) complex from neural cells by biochemical purification. In so doing, we identified myelin transcription factor 1 (MyT1) as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor, and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed that the Pten gene was directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation.

Early detection of ovarian and fallopian tube cancer by examination of cytological samples from the endometrial cavity.

BACKGROUND: Accumulating evidence suggests that many ovarian high-grade serous carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal lesions can be detected by examination of cytological samples from the endometrial cavity (endometrial cytological testing). To evaluate the use of this method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and primary peritoneal cancer patients. METHODS: Endometrial cytological testing was performed for endometrial cancer screening in asymptomatic women and for pre-treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal cancer patients. RESULTS: Of the 122 ovarian, tubal, and peritoneal cancer patients, malignant cells were identified in 5 patients who did not show detectable abnormalities on imaging studies. Cervicovaginal cytology was positive in only one of these five patients. Four patients were asymptomatic and one was symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other asymptomatic patient had positive peritoneal cytology findings but no detectable tumour. HGSC patients were significantly more likely to have positive findings on endometrial cytology than patients with other histological types (23% vs 6%, P=0.02). CONCLUSION: Endometrial cytological testing can detect early-stage ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be useful for ovarian cancer screening.

Lymphadenectomy and adjuvant therapy in endometrial carcinoma: role of adjuvant chemotherapy.

To evaluate the therapeutic benefit of lymphadenectomy and adjuvant therapy, in particular chemotherapy, we retrospectively analysed survival rates and patterns of recurrence of endometrioid adenocarcinoma in 106 patients who underwent surgery including retroperitoneal lymphadenectomy. Adjuvant chemotherapy was administered to 46 patients (42 received a platinum-based regimen) and pelvic irradiation to 12. The 5-year survival rate of 23 patients with lymph node metastasis was worse than that of patients without lymph node metastasis (60% vs 96%, P<0.0001). Recurrence was observed in 14 patients (10 patients with chemotherapy, two with irradiation, and two without adjuvant therapy); the first site of recurrence was in distant sites in 12 patients; recurrence in the pelvic sidewall or exclusively in lymph nodes was not observed. The 5-year survival rate of 18 patients with lymph node metastasis treated with chemotherapy, was 61% including all 14 with macroscopically positive nodes and all nine with paraaortic metastasis. Of seven patients with bulky positives nodes, three patients with bulky paraaortic nodes died of the disease, three of the four patients with bulky pelvic but without bulky paraaortic nodes had no recurrence. In summary, lymphadenectomy may afford a survival benefit via the debulking of macroscopically positive nodes, and the predominance of distant recurrences suggests that chemotherapy is a suitable choice as an adjuvant therapy in endometrial carcinoma after lymphadenectomy.

Pulmonary metastasis from endometrial carcinoma.

The objective of this article is to investigate the clinical features of pulmonary metastasis (PM) from endometrial adenocarcinoma, in particular, the predictors of prolonged survival after PM detection. Fifteen patients who developed PM and underwent chest computed tomography (CT) scans for evaluation of PM were studied: 12 patients with pulmonary recurrence and 3 patients with PM on presentation. All patients with bilateral nodules or lymphangitic spread had metastases in other sites prior to or concomitant with PM, most of which were detected in para-aortic lymph nodes and/or the vaginal wall, while only one of five patients with a limited number (n < or = 5) of unilateral nodules had these metastases. The median survival time for the 10 patients with bilateral PMs was significantly shorter than that of the 5 patients with a limited number of unilateral nodules who were treated with surgery (7 versus 50 months, P = 0.005). Patients who developed pulmonary recurrence 2 years after the initial therapy had a significantly longer survival than those who developed it within 2 years (31 versus 10 months, P = 0.01). In conclusion, the distribution of PM determined by CT scans and the time interval between the initial therapy and the detection of pulmonary recurrence are the predictors of survival after PM detection.

[The significance of invasion and vessel permeation in squamous cell carcinoma of the uterine cervix with invasion to a depth of 3 mm or less].

Nine-five patients with squamous cell carcinoma of the cervix invading to a depth of 3 mm or less (microinvasive carcinoma) were retrospectively viewed in regard to the depth of stromal invasion, the width of horizontal spread, confluent invasion, vessel permeation and lymph node metastasis. The type of treatment and outcome were also evaluated. Confluent invasion was found in 6 patient (6%), and vessel permeation in 9 patients (9%). Lymph node dissections were performed on 85 patients, but no lymph node metastasis was found, irrespective of the presence of confluent invasion or vessel permeation. Fifty-five patients with no vessel permeation were treated by conization or total or modified racial hysterectomy, and none had a recurrence of the disease. Our results suggest that the presence of confluent invasion or vessel permeation does not influence the incidence of lymph node metastasis, but data in the literature indicate that confluent invasion and vessel permeation are risk factors for lymph node metastasis and invasive recurrence of the disease. We conclude that patients with invasion of depth 3m or less, with no confluent invasion and no vessel permeation, can be treated by conservative operation.