ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis.

The excision repair cross completing group 1 gene product (ERCC1) and the regulatory subunit of ribonucleotide reductase (RRM1) have been reported as being prognostic of outcome and predictive of therapeutic efficacy in patients with non-small cell lung cancer. Routinely processed surgical specimens from 784 patients from the International Adjuvant Lung Trial were arrayed as tissue microarrays. In situ protein levels were scored with an automated, quantitative analysis system, dichotomized into high and low marker categories, and analyzed for associations with patients' characteristics, survival, and benefit from adjuvant chemotherapy.

Complex cell cycle abnormalities caused by human T-lymphotropic virus type 1 Tax.

Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL), a malignancy of CD4(+) T cells whose etiology is thought to be associated with the viral trans-activator Tax. We have shown recently that Tax can drastically upregulate the expression of p27(Kip1) and p21(CIP1/WAF1) through protein stabilization and mRNA trans-activation and stabilization, respectively. The Tax-induced surge in p21(CIP1/WAF1) and p27(Kip1) begins in S phase and results in cellular senescence.

Optimism bias leads to inconclusive results-an empirical study.

Objective: Optimism bias refers to unwarranted belief in the efficacy of new therapies. We assessed the impact of optimism bias on a proportion of trials that did not answer their research question successfully and explored whether poor accrual or optimism bias is responsible for inconclusive results.

Study Design: Systematic review.

Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma.

Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e.

Prognostic factor analyses of myeloma survival with intergroup trial S9321 (INT 0141): examining whether different variables govern different time segments of survival.

Multiple myeloma (MM) survival plots usually display steeper initial and shallower subsequent slopes reflecting differences in disease biology and likely prognostic factors (PF). S9321 trial was selected to determine PF operative at baseline and subsequent 3, 4, 5, and 7-year landmarks (LM-0, LM-3, LM-4, LM-5, and LM-7). With a median follow-up of 8.

Genetic and phenotypic diversity in Burkholderia: contributions by prophage and phage-like elements.

Background: Burkholderia species exhibit enormous phenotypic diversity, ranging from the nonpathogenic, soil- and water-inhabiting Burkholderia thailandensis to the virulent, host-adapted mammalian pathogen B. mallei. Genomic diversity is evident within Burkholderia species as well.

A femtomole-sensitivity mass assay for inositol hexakisphosphate.

Inositol hexakisphosphate (InsP(6)) is an important component of cells, and its mass levels are usually assayed by either (a) equilibrium labelling of cell cultures with radiolabelled inositol or (b) by a variety of mass assays of differing sensitivities and ambiguities. Here, we describe a mass assay for InsP(6) that is based on phosphorylating InsP(6) with [(32)P]-ATP to 5-(PP)InsP(5) using a recombinant Giardia InsP(6) kinase and quantification of the radiolabelled 5-[(32)P](PP)InsP(5) product by anion exchange HPLC with an internal [(3)H]-(PP)InsP(5) standard. Interference with the enzyme reaction by other factors in the tissue extract is corrected for by assay of identical aliquots of tissue spiked with known amounts of InsP(6).

Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.

Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes.

Next generation 1.5 microm terahertz antennas: mesa-structuring of InGaAs/InAlAs photoconductive layers.

Mesa-structuring of InGaAs/InAlAs photoconductive layers is performed employing a chemical assisted ion beam etching (CAIBE) process. Terahertz photoconductive antennas for 1.5 microm operation are fabricated and evaluated in a time domain spectrometer.

Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-small-cell lung cancer.

Purpose: Src family kinase (SFK) proteins are frequently activated in cancer and can coordinate tumor cell growth, survival, invasion, and angiogenesis. Given the importance of SFK signaling in cancer, known cooperation between SFK and epidermal growth factor receptor (EGFR) signaling, and efficacy of EGFR inhibitors, we performed a phase I trial combining dasatinib, an SFK and multikinase inhibitor, with erlotinib, an EGFR inhibitor, in patients with advanced non-small-cell lung cancer.

Patients And Methods: Patients received erlotinib for 1 week before addition of dasatinib; pharmacokinetics were performed after weeks 1 and 2.

Features of potentially predictive biomarkers of chemotherapeutic efficacy in small cell lung cancer.

Introduction: One-size-fits-all chemotherapy does not improve survival in patients with small cell lung cancer (SCLC). Excision repair cross-complementing group 1 (ERCC1), ribonucleotide reductase 1 (RRM1), thymidylate synthase (TS), and topoisomerase 2alpha (Topo2alpha) expression levels are predictive of chemotherapeutic efficacy in some malignancies. Our aim was to determine the expression levels of these proteins to assess their potential clinical utility in SCLC.

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling.

The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P(3)] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P(3). These enzymes terminate the signal to release Ca(2+) from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P(4)].

The false discovery rate: a key concept in large-scale genetic studies.

Background: In experimental research, a statistical test is often used for making decisions on a null hypothesis such as that the means of gene expression in the normal and tumor groups are equal. Typically, a test statistic and its corresponding P value are calculated to measure the extent of the difference between the two groups. The null hypothesis is rejected and a discovery is declared when the P value is less than a prespecified significance level.

[The "do-not-resuscitate order" in paediatric palliative home care: why should the emergency team be involved ?].

Major challenge in paediatric palliative home care is to anticipate management of future events. In our opinion, one of major approach is to avoid medical futility especially resuscitation attempts in terminally-ill children especially if home care will be organized. We therefore prospectively discussed with proxi what should be attempted (e.

[A positioning pillow to improve lumbar puncture in paediatric haematology-oncology patients: a randomized controlled trial.].

ObjectivesLumbar punctures (LPs) are common in children with cancer. Although pain management during the LP has been well standardised, dealing with stress and anxiety is not well addressed yet. Our objective was to evaluate the potential improvement of the LPs success rate using a positioning pillow, to ensure maximum lumbar flexion, and allow paravertebral muscles to relax, in children who are awake, with either conscious sedation or no sedation.

In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-based chemotherapy.

Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small-cell lung cancer and pancreatic cancer. We investigated the protein levels of RRM1 and two other DNA repair enzymes, ERCC1 and BRCA1, in 55 metastatic breast cancer (MBC) patients undergoing gemcitabine-based chemotherapy. With automated in situ protein quantification (AQUA v1.

Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer.

Purpose: We evaluated the efficacy of gemcitabine versus gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC) and a performance status (PS) of 2 and assessed if tumoral RRM1 and ERCC1 protein levels are predictive of response to therapy.

Patients And Methods: A randomized phase III trial was conducted in community-based oncology practices. Tumor specimens were collected a priori and shipped to a single laboratory for blinded determination of in situ RRM1 and ERCC1 protein expression levels by an automated quantitative immunofluorescent-based technology.

Neuronal IP3 3-kinase is an F-actin-bundling protein: role in dendritic targeting and regulation of spine morphology.

The actin microstructure in dendritic spines is involved in synaptic plasticity. Inositol trisphosphate 3-kinase A (ITPKA) terminates Ins(1,4,5)P(3) signals emanating from spines and also binds filamentous actin (F-actin) through its amino terminal region (amino acids 1-66, N66). Here we investigated how ITPKA, independent of its kinase activity, regulates dendritic spine F-actin microstructure.

Analysis of group randomized trials with multiple binary endpoints and small number of groups.

The group randomized trial (GRT) is a common study design to assess the effect of an intervention program aimed at health promotion or disease prevention. In GRTs, groups rather than individuals are randomized into intervention or control arms. Then, responses are measured on individuals within those groups.

[Hodgkin's disease: treatment specificities in childhood].

Paediatric Hodgkin disease presents some particularities when compared to Hodgkin in adults. In this article, we focus on the paediatric particularities, especially in term of current treatment strategy. The aim is to decrease the important rate of late effects while keeping the excellent survival.

Continuous wave terahertz systems exploiting 1.5 microm telecom technologies.

A fiber-assembled CW THz System operating at 1.5 microm is presented. High speed telecom photodiodes integrated with planar THz antennas serve as THz emitters with power up to 10 microW.

Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD.

Patients on systemic glucocorticoids for GVHD after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole or fluconazole vs itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD who were administered voriconazole (n=97), fluconazole (n=36) or itraconazole (n=36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole vs 2/97 (2%) on voriconazole (P=0.

Mirk/Dyrk1B, a novel therapeutic target, mediates cell survival in non-small cell lung cancer cells.

Minibrain-related kinase (Mirk) is a member of the dual specificity tyrosine-phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases and is identical to Dyrk1B. Mirk/Dyrk1B is a serine/threonine kinase that has been found to be upregulated in solid tumors and mediates cell survival in colon cancer, pancreatic ductal adenocarcinoma and rhabdomyosarcomas. There is little known about Mirk in lung cancer.