Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for HS Mediated Persulfidation.

The gasotransmitter hydrogen sulfide (HS) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by Zn, O, and HS, with intermediates involving oxygen- and sulfur-based radicals detected by mass spectrometry and optical spectroscopies.

The Impact of a National Cyberattack Affecting Clinical Trials: The Cancer Trials Ireland Experience.

Purpose: Cyberattacks are increasing in health care and cause immediate disruption to patient care, have a lasting impact, and compromise scientific integrity of affected clinical trials. On the May 14, 2021, the Irish health service was the victim of a nationwide ransomware attack. Patient care was disrupted across 4,000 locations, including 18 cancer clinical trials units associated with Cancer Trials Ireland (CTI).

Magnetic fields of 30 to 100 kG in the cores of red giant stars.

A red giant star is an evolved low- or intermediate-mass star that has exhausted its central hydrogen content, leaving a helium core and a hydrogen-burning shell. Oscillations of stars can be observed as periodic dimmings and brightenings in the optical light curves. In red giant stars, non-radial acoustic waves couple to gravity waves and give rise to mixed modes, which behave as pressure modes in the envelope and gravity modes in the core.

Geometrical variations of two manganese(II) complexes with closely related quinoline-based tripodal ligands.

Structural analyses of the compounds di-μ-acetato-κ :'-bis-{[2-meth-oxy-,-bis-(quinolin-2-ylmeth-yl)ethanamine-κ ,','',]manganese(II)} bis-(tetra-phen-yl-borate) di-chloro-methane 1.45-solvate, [Mn(CO)(CHNO)](CHB)·1.45CHCl or [Mn(DQMEA)(μ-OAc)Mn(DQMEA)](BPh)·1.

Effects of HER Family-targeting Tyrosine Kinase Inhibitors on Antibody-dependent Cell-mediated Cytotoxicity in HER2-expressing Breast Cancer.

Purpose: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one mechanism of action of the monoclonal antibody (mAb) therapies trastuzumab and pertuzumab. Tyrosine kinase inhibitors (TKIs), like lapatinib, may have added therapeutic value in combination with mAbs through enhanced ADCC activity. Using clinical data, we examined the impact of lapatinib on HER2/EGFR expression levels and natural killer (NK) cell gene signatures.

Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project.

Background: The optimal timing of (neo)adjuvant trastuzumab initiation with respect to chemotherapy and surgery remains undefined.

Methods: Retrospective analysis of a large institutional database of HER2-positive patients who received anti-HER2 therapy. We included all Stage I to III patients treated with trastuzumab with a minimum follow up of 3 years.

Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database.

Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients.

Background: Serum profiling using mass spectrometry-based proteomic techniques has great potential to detect biomarkers that might improve the management for advanced breast cancer patients. The albuminome has previously been investigated as a tool in biomarker discovery, however other high abundant blood proteins are also likely to sequester potentially interesting molecules.

Methods: Affinity resin purified and isolated Transferrin and associated bound proteins from normal control and breast cancer patient serum samples were analysed by label-free mass spectrometry during the discovery phase.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer.

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application.

Seismic constraints on rotation of Sun-like star and mass of exoplanet.

Rotation is thought to drive cyclic magnetic activity in the Sun and Sun-like stars. Stellar dynamos, however, are poorly understood owing to the scarcity of observations of rotation and magnetic fields in stars. Here, inferences are drawn on the internal rotation of a distant Sun-like star by studying its global modes of oscillation.

Evaluation of IGF1R and phosphorylated IGF1R as targets in HER2-positive breast cancer cell lines and tumours.

Insulin-like growth factor-1 receptor (IGF1R) signalling is implicated in resistance to trastuzumab. However, the benefit of co-targeting HER2 and IGF1R has not been extensively studied, and the relationship between activated IGF1R and clinical response to trastuzumab has not been reported. This study aimed to evaluate the combination of trastuzumab with IGF1R tyrosine kinase inhibitors (TKIs) in a panel of HER2-positive breast cancer cell lines, and to examine the relationship between IGF1R expression and activation and response to trastuzumab in HER2-positive breast cancer patients.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer.

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits.

Ensemble asteroseismology of solar-type stars with the NASA Kepler mission.

In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.

CoRoT reveals a magnetic activity cycle in a Sun-like star.

The 11-year activity cycle of the Sun is a consequence of a dynamo process occurring beneath its surface. We analyzed photometric data obtained by the CoRoT space mission, showing solarlike oscillations in the star HD49933, for signatures of stellar magnetic activity. Asteroseismic measurements of global changes in the oscillation frequencies and mode amplitudes reveal a modulation of at least 120 days, with the minimum frequency shift corresponding to maximum amplitude as in the Sun.

Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis.

Background: Malignant melanoma, generally described as incurable, is notoriously refractory to chemotherapy. The mechanisms contributing to this have not yet been defined and the contributions of drug efflux pumps, implicated in chemo-resistance of many other cancer types, have not been extensively investigated in melanoma.

Methods: In this study, expression of multi-drug resistant (MDR1/P-gp and MRP-1) proteins was examined, by immunohistochemistry, in archival specimens from 134 melanoma patients.

Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

Background: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease.

Methods: In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients.

CoRoT measures solar-like oscillations and granulation in stars hotter than the Sun.

Oscillations of the Sun have been used to understand its interior structure. The extension of similar studies to more distant stars has raised many difficulties despite the strong efforts of the international community over the past decades. The CoRoT (Convection Rotation and Planetary Transits) satellite, launched in December 2006, has now measured oscillations and the stellar granulation signature in three main sequence stars that are noticeably hotter than the sun.

2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteins.

Most lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples.

MDR1/P-glycoprotein and MRP-1 drug efflux pumps in pancreatic carcinoma.

Background: Pancreatic cancer is one of the most challenging solid organ malignancies. This is due to its aggressiveness, frequent late presentation as advanced disease and chemoresistance. A better understanding of the molecular basis of its drug resistance is needed.

MDR1/P-glycoprotein and MRP-1 mRNA and protein expression in non-small cell lung cancer.

Background: Multiple drug resistance (MDR), both inherent and acquired, is a serious problem in non-small cell lung carcinomas (NSCLC). The purpose of this study was to investigate the prevalence of expression of genes encoding drug efflux pumps, MDR1 and MRP-1, at both the mRNA and protein levels, in this type of cancer.

Materials And Methods: Tumour specimens (38 cases) were analysed using immunohistochemistry and, where possible (30 cases), also using reverse-transcriptase polymerase chain reaction.

Tracking solar gravity modes: the dynamics of the solar core.

Solar gravity modes have been actively sought because they directly probe the solar core (below 0.2 solar radius), but they have not been conclusively detected in the Sun because of their small surface amplitudes. Using data from the Global Oscillation at Low Frequency instrument, we detected a periodic structure in agreement with the period separation predicted by the theory for gravity dipole modes.

A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer.

Purpose: Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g.

Surprising sun: a new step towards a complete picture?

Important revisions of the solar model ingredients have appeared recently. We first show that the updated CNO composition suppresses the anomalous position of the Sun in the known galactic enrichment. The following law, He/H = 0.