3D CMOS/molecular hybrid circuits.

CMOS/nanowire/nanodevice (CMOL) hybrid circuit promises great opportunities for future hybrid nano-scale integrated circuit implementation. In order to improve the fabrication and performance of CMOL circuits, a novel three dimension (3D) architecture is introduced in this work. 3D CMOL eliminates this special pin requirement, enabling feasible fabrication.

Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy.

Background: Amplification or deletion of the topoisomerase II alpha (TOP2A) gene in breast cancers has been postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than amplification of the human epidermal growth factor receptor type 2 (HER2) gene.

Methods: We studied 438 tumors from 710 premenopausal women with node-positive breast cancer who received cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy in the randomized National Cancer Institute of Canada Clinical Trials Group Mammary 5 (MA.5) trial.

Alternate endpoints for screening phase II studies.

Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development and those for which further evaluation should be halted. Although definitive phase III trials use progression-free or overall survival to confirm clinical benefit, earlier endpoints are preferable for phase II trials. Traditionally, tumor shrinkage of a predetermined degree (response) has been used as a surrogate of eventual survival benefit based on the observation that high response rates (RR), and particularly complete responses, in the phase II setting resulted in survival benefit in subsequent phase III trials.

Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial.

Purpose: National Cancer Institute of Canada Clinical Trials Group CO.17 demonstrated the antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab improves overall and progression-free survival in patients with advanced, chemotherapy-refractory colorectal cancer (CRC), particularly in patients with wild-type KRAS tumors. This article reports the health-related quality-of-life (HRQL) outcomes from CO.

Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.

Lys-48-linked polyubiquitination regulates a variety of cellular processes by targeting ubiquitinated proteins to the proteasome for degradation. Although polyubiquitination had been presumed to occur by transferring ubiquitin molecules, one at a time, from an E2 active site to a substrate, we recently showed that the endoplasmic reticulum-associated RING finger ubiquitin ligase gp78 can mediate the preassembly of Lys-48-linked polyubiquitin chains on the catalytic cysteine of its cognate E2 Ube2g2 and subsequent transfer to a substrate. Active site-linked polyubiquitin chains are detected in cells on Ube2g2 and its yeast homolog Ubc7p, but how these chains are assembled is unclear.

Outcomes of a remote, decentralized health center-based HIV/AIDS antiretroviral program in Zambia, 2003 to 2007.

A cross-sectional study of patients living with HIV/ AIDS treated during 2003 to 2007 in decentralized, rural health centers in Zambia was performed to measure virological outcomes after 12 months of antiretroviral therapy and identify factors associated with virological failure. Data from 228 patients who started antiretroviral therapy >12 months prior were analyzed. In all, 93% received stavudine + lamivudine + nevirapine regimens, and median antiretroviral therapy duration was 23.

High extracellular potassium ion concentration attenuates the blockade action of ketanserin on Kv1.3 channels expressed in xenopus oocytes.

Background: Ketanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances.

A randomized, double-blind, controlled trial of perioperative administration of gabapentin, meloxicam and their combination for spontaneous and movement-evoked pain after ambulatory laparoscopic cholecystectomy.

Background: Hysterectomy and spinal surgery inpatient trials suggest favorable interactions between cyclooxgenase-2 inhibitors and gabapentin/pregabalin on postoperative days 1-2. We present the first trial of meloxicam-gabapentin combination after outpatient laparoscopic cholecystectomy.

Methods: This was a randomized, double-blind trial comparing daily oral administration of 1) meloxicam 15 mg, 2) gabapentin 1200-1600 mg, and 3) a combination of the two starting 1 h before until 2 days after surgery.

The Colon Health and Life-Long Exercise Change trial: a randomized trial of the National Cancer Institute of Canada Clinical Trials Group.

Background: Observational studies indicate that physical activity (PA) is strongly associated with improved disease outcomes in colon cancer survivors, but a randomized controlled trial is needed to determine whether the association is causal and whether new policies to promote exercise are justified.

Purpose: The co.21 Colon Health and Life-Long Exercise Change (challenge) trial undertaken by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) is designed to determine the effects of a structured pa intervention on outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant therapy within the previous 2-6 months.

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

Background: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival.

[Analysis and analyzing mechanisms of HERG channel kinetics].

We have investigated the methods and mechanisms for analysis of the channel kinetics parameters of voltage-gated potassium channels, HERG (Human ether-à-go-go related gene) channels, in the process of electrophysiological recording. The current of HERG K+ channels expressed in Xenopus oocytes was studied using a two-electrode voltage clamp technique, and the channel kinetics parameters were analyzed through compiling different pulse protocol and recording the current. Results showed: (1) The HERG K+ channels, under conditions of being activated with depolarized pulse, expressed an inward-rectified property attributing to rapid inactivation.

Quercetin activates human Kv1.5 channels by a residue I502 in the S6 segment.

1. The aims of the present study were to investigate the pharmacological effects of quercetin on wild-type (WT) and mutant (I502A) human (h) Kv1.5 channel currents (I(kur)) and to identify whether mutation in the S6 segment is critical to activation of I(kur) by quercetin.

K-ras mutations and benefit from cetuximab in advanced colorectal cancer.

Background: Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value.

Methods: We analyzed tumor samples, obtained from 394 of 572 patients (68.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

Purpose: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT.

Methods And Materials: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center.

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.

Purpose: Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.

Noise reduction by diffusional dissipation in a minimal quorum sensing motif.

Cellular interactions are subject to random fluctuations (noise) in quantities of interacting molecules. Noise presents a major challenge for the robust function of natural and engineered cellular networks. Past studies have analyzed how noise is regulated at the intracellular level.

Blockade of the human ether-a-go-go-related gene potassium channel by ketanserin.

In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels expressed in Xenopus oocytes and the effects of changing the channel molecular determinants characteristics on the blockade with and without ketanserin intervention using standard two-microelectrode voltage-clamp techniques. Point mutations were introduced into HERG gene (Y652A and Y652R) and subcloned into the pSP64 plasmid expression vector. Complementary RNAs for injection into oocytes were prepared with SP6 Cap-Scribe after linearization of the expression construct with EcoR I.

Phase II stopping rules that employ response rates and early progression.

Purpose: Phase II oncology trials traditionally have used response rate (RR) as the primary end point, but newer targeted agents require the consideration of alternative end points. High rates of early progressive disease (EPD) suggest inadequate drug activity and may be useful in the early stopping of trials. This study used a simulation to define a set of rules to assess a combined end point of RR and EPD.

[The persistent expression of HERG channel in Xenopus oocyte and alteration of current].

Aim: To explore a method of the stable and persistent expression of HERG(human ether-a-go-go-related gene) channels in Xenopus oocytes, and investigate the alteration of rest membrane potential of oocytes and electrophysiological properties of expressed channel in different culture duration.

Methods: HERG mRNA for injection was prepared with in intro transcription using vector plasmid pSP64 containing HERG cDNA fragment. Expressed HERG current was recorded using standard two-microelectrode voltage-clamp technique.

Electropharmacological properties of telmisartan in blocking hKv1.5 and HERG potassium channels expressed on Xenopus laevis oocytes.

Aim: The objectives of this study were to investigate the inhibitory action of telmisartan, a selective angiotensin II type 1 receptor antagonist, on hKv1.5 and human ether-a-go-go-related gene (HERG) channels expressed on Xenopus laevis oocytes.

Methods: hKv1.

NCIC Clinical Trials Group experience of employing patient-reported outcomes in clinical trials: an illustrative study in a palliative setting.

In this article we briefly review the experience of the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) with respect to the assessment of patient reported outcomes in clinical trials, and illustrate issues important to assessing symptom palliation in clinical trials of cancer therapy. We highlight a standard approach taken by the NCIC CTG, and illustrate how this approach may be applied to the complex problem of symptom control analysis in patients with locally advanced NSCLC. We further illustrate how variations in this analysis yield different apparent rates of palliation.

Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group.

Purpose: AZD2171 is a potent inhibitor of vascular endothelial growth factor receptors that showed broad antitumor activity in preclinical models. Doses of up to 45 mg/d of AZD2171 are tolerable when administered alone. This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non-small-cell lung cancer.

Use of pelvic lymphoscintigraphy to demonstrate lymphoid fluid leakage in an ovarian cancer patient with chylous ascites.

Despite radiotherapy and chemotherapy, chylous ascites occur frequently in patients with ovarian cancer. We report a case of ovarian cancer with massive chylous ascites and describe the use of lymphoscintigraphy to demonstrate pelvic lymph nodes and lymphoid fluid leakage to the pelvic floor.