Cancer biomarker discovery using selected ion flow tube mass spectrometry

Lung cancer is one of the most common types of neoplasm and is a leading cause of death in Canada. Accurate early diagnosis is key to the effective treatment of the disease, however the current means to do so, such as Computed Tomography diagnostic imaging, are costly, invasive, and not practical for routine use. The detection of volatile cancer biomarkers in breath represents an attractive non-invasive means to diagnose the disease. It is unclear, however, which, if any, breath chemicals have diagnostic utility. In this thesis I used Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), a trace gas analytic method to (a) identify potential volatile cancer biomarkers in blood, and (b) investigate whether these markers are present in breath. Potential biomarkers were identified by comparing products ions formed in the reaction between hydronium (H3O+) and nitronium (NO+) precursor ions and trace gases present in the headspace of plasma obtained from patients with breast cancer, colorectal or lung cancer, and healthy controls. Using this approach product ions of interest were identified which derive from a wide range of chemical classes including aldehydes, acids, alcohols and sulphides, including some which have been identified previously by other investigators. Many of these ions could be quantified in the breath of healthy controls and therefore be suitable for quantification by breath analysis. The production rate of most of these ions was, however, poorly correlated between those formed in the reactions between nasal breath and those formed in reactions with blood headspace, even when using in samples collected and analysed simultaneously from the same participants. The lack of correlation suggests that the breath trace gases from which these product ions are formed are not dependent on the blood concentration of the same gas, but likely derive mainly from the airways. As such while my data suggest that cancer biomarkers may be found in the bloodstream, breath analysis is not a suitable means to non-invasively detect these cancer markers, in particular cancers of tissues other than those found in the airway. On the other hand, my data suggests that the detection of airway disease, including that of lung cancer, may be suitable candidates for the diagnosis and/or screening using breath analysis

Assessment of Nurses’ Adherence to The Centers for Disease Control and Prevention (CDC) Guidelines Regarding Central Line Care for Children with Cancer

Using Central Line Catheters (CLCs) is actually an essential element of modern healthcare throughout the world. Central Line Associated Bloodstream Infections (CLABSI) accounts for 11% of all health care association infection which increases the cost of health care and prolongs hospitalization. Nurses play an intrinsic role in preventing CLABSIs through following the CDC guidelines recommendations. This study aimed to assess Oncology nurses' adherence to CDC guidelines regarding CLC care for children with cancer at Pediatric Oncology Units, King Fahad Specialist Hospital in Dammam (KFSH-D). A descriptive research design was utilized and 25 pediatric oncology nurses who were providing Central Line Catheter care for children with cancer have participated in this study. Every nurse was observed for three different times while providing CLC care. Results: The participant nurses from pediatric oncology inpatient constituted 64% while outpatient nurses were 36% of the sample. The total adherence median percent score (IQR) for inpatients nurses was 79% (14%), while outpatients nurses adherence median percent score (IQR)was 76% (12%). No significant statistical different found between the two groups. Conclusion; although the strict adherence to CDC guidelines regarding CLC care is highly recommended the study illustrated that the adherence of the nurses was not efficient. Recommendations: Training sessions to improve nurses' skills regarding CLC care. Periodical competencies check off to assess the level of nurses' adherence to CDC guidelines are recommended. Further researches to assess CLC care practice are required with larger sample size. Keywords: Central line catheter care, children with cance

Linear Optical, Quadratic and Cubic Nonlinear Optical, Electrochemical, and Theoretical Studies of "Rigid-Rod" Bis-Alkynyl Ruthenium Complexes

The syntheses of oligo(p‐phenylene ethynylene)s (OPEs) end‐functionalized by a nitro acceptor group and with a ligated ruthenium unit at varying locations in the OPE chain, namely, trans‐[Ru{(C≡C‐1,4‐C6H4)nNO2}(C≡CR)(dppe)2] (dppe=1,2‐bis(diphenylphosphino)ethane; n=1, R=1,4‐C6H4C≡C‐1,4‐C6H4C≡CPh, 1,4‐C6H4NEt2; n=2, R=Ph, 1,4‐C6H4C≡CPh, 1,4‐C6H4C≡C‐1,4‐C6H4C≡CPh, 1,4‐C6H4NO2, 1,4‐C6H4NEt2; n=3, R=Ph, 1,4‐C6H4C≡CPh), are reported. Their electrochemical properties were assessed by cyclic voltammetry, their linear optical properties and quadratic and cubic nonlinear optical properties were assayed by UV/Vis/NIR spectroscopy, hyper‐Rayleigh scattering studies employing nanosecond pulses at 1064 nm, and broad spectral range Z‐scan studies employing femtosecond pulses, respectively, and their linear optical properties and vibrational spectroscopic behavior in the formally RuIII state was examined by UV/Vis/NIR and IR spectroelectrochemistry, respectively. The potentials of the metal‐localized oxidation processes are sensitive to alkynyl‐ligand modification, but this effect is attenuated on π‐bridge lengthening. Computational studies employing time‐dependent density functional theory were undertaken on model complexes, with a 2D scan revealing a soft potential‐energy surface for intra‐alkynyl‐ligand aryl‐ring rotation; this is consistent with the experimentally observed blueshift in optical absorption maxima. Quadratic optical nonlinearities are significant and cubic NLO coefficients for these small complexes are small. The optimum length of the alkynyl ligands and the ideal metal location in the OPE to maximize the key coefficients have been defined.We thank the Australian Research Council, the Fund for Scientific Research–Flanders (FWO-Vlaanderen; FWO G.0312.08), and the Katholieke Universiteit Leuven (GOA/2006/03) for financial support, and Yuwen Wu (ANU) for providing a crystal of 14 suitable for the X-ray diffraction study

DNA-binding and anticancer activity of binuclear gold(I) alkynyl complexes with a phenanthrenyl bridging ligand

3,6-Diethynyl-9,10-diethoxyphenanthrene (4) was synthesized from phenanthrene and employed in the synthesis of the binuclear gold(I) alkynyl complexes (R3P)Au(C≡C-3-[C14H6-9,10-diethoxy]-6-C≡C)Au(PR3) (R = Ph (5a), Cy (5b)). The diyne 4 and complexes 5a and 5b were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV-Vis spectroscopy studies of the metal complexes and precursor diyne show strong π → π* transitions in the near UV region that red shift by ca. 50 nm upon coordination at the gold centers. The emission spectrum of 4 shows an intense fluorescence band centered at 420 nm which red shifts, slightly upon coordination of 4 to gold. Binding studies of 4, 5a, and 5b against calf thymus DNA were carried out, revealing that 4, 5a, and 5b have ≥40% stronger binding affinities than the commonly used intercalating agent ethidium bromide. The molecular docking scores of 4, 5a, and 5b with B-DNA suggest a similar trend in behavior to that observed in the DNA-binding study. Unlike the ligand 4, promising anticancer properties for 5a and 5b were observed against several cell lines; the DNA binding capability of the precursor alkyne was maintained, and its anticancer efficacy enhanced by the gold centers. Such phenanthrenyl complexes could be promising candidates in certain biological applications because the two components (phenanthrenyl bridge and metal centers) can be altered independently to improve the targeting of the complex, as well as the biological and physicochemical properties.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-44-130-40). The authors, therefore, acknowledge with thanks DSR technical and financial support

A Subcutaneous Juvenile Xanthogranuloma in a 4-Year-Old Girl Who Presented with a Lower Eyelid Mass

Juvenile xanthogranuloma (JXG) is a relatively uncommon, benign, histiocytic proliferative cutaneous disorder that typically affects children, with the head and neck being the most common sites. The present case report describes an isolated subcutaneous JXG in a 4-year-old girl who presented with a circumscribed oval mass located in the lower eyelid of the right eye. This lesion was histologically diagnosed as JXG after a surgical resection of the mass

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands

Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru-Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-60-130-38)

Full-term extrauterine abdominal pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Extrauterine abdominal pregnancy is extremely rare and is frequently missed during antenatal care. This is a report of a full-term extrauterine abdominal pregnancy in a primigravida who likely had a ruptured ectopic pregnancy with secondary implantation and subsequently delivered a healthy baby.</p> <p>Case presentation</p> <p>A 23-year-old, Middle Eastern, primigravida presented at 14 weeks gestation with intermittent suprapubic pain and dysuria. An abdominal ultrasound examination showed a single viable fetus with free fluid in her abdomen. A follow-up examination at term showed a breech presentation and the possibility of a bicornute uterus with the fetus present in the left horn of her uterus. Our patient underwent Cesarean delivery under general anesthesia and was found to have a small intact uterus with the fetus lying in her abdomen and surrounded by an amniotic fluid-filled sac. The baby was extracted uneventfully, but the placenta was implanted in the left broad ligament and its removal resulted in massive intraoperative bleeding that necessitated blood and blood products transfusion and the administration of Factor VII to control the bleeding. Both the mother and newborn were discharged home in good condition.</p> <p>Conclusions</p> <p>An extrauterine abdominal pregnancy secondary to a ruptured ectopic pregnancy with secondary implantation could be missed during antenatal care and continue to term with good maternal and fetal outcome. An advanced extrauterine pregnancy should not result in the automatic termination of the pregnancy.</p

The potential anticancer activities of platinum(II) complexes with tridentate N'N'N' pincer ligands

519-530Treatment of cis/trans-[PtCl2(N&equiv;CR)2] 1 (R = CH3 (1a), C2H5 (1b), C6H5 (1c), CH2C6H4(p-CH3) (1d)) with 1,3-diiminoisoindoline 2 gives access to the corresponding symmetrical (1,3,5,7,9-pentaazanona-1,3,6,8-tetraenato) platinum(II) complexes [PtCl{NH=C(R)N=C(C6H4)NC=NC(R)=NH}] 3a-d, in good yields (65&ndash;77%). The compounds 3a-d have been characterized by IR, 1H, 13C and DEPT-135 NMR spectroscopies, ESI-MS and elemental analyses. GIAO/DFT studies have been performed to confirm the molecular structure of the platinum(II)-pincer 3d by comparing the experimental and theoretical 1H and 13C NMR chemical shifts, and it has shown good correlations between experimental and calculated chemical shifts for proton and carbon with correlation coefficients of 0.9947 and 0.9968, respectively. Molecular electrostatic potential is used to investigate the nucleophilic or electrophilic regions in the molecule 3d. The antimicrobial activities of compounds 3a-d are determined against different bacterial pathogens and yeasts. No toxicity is recorded against Artemia saline as a test organism for 3a-c, while moderate toxicity is found for 3d at 0.62 &micro;M. Comparable antitumor activities are found for 3a-d against human colon HCT116 and human breast (MCF-7) cancer cell lines. The complexes 3a-d have shown good binding affinities to ct-DNA in the range of 6.00&acute;105 to 8.33&acute;105 and the conducted molecular docking studies suggest an intercalation mode of binding with DNA by the isoindole fragment of the ligands. Overall, this class of tridentate ligands have shown good potential in designing platinum(II) complexes with promising biological and anticancer activities. Moreover, the presence of the side chains on the ligands provides great design flexibility by introducing some chemical and/or physical characteristics

The potential anticancer activities of platinum(II) complexes with tridentate N'N'N' pincer ligands

Treatment of cis/trans-[PtCl2(N≡CR)2] 1 (R = CH3 (1a), C2H5 (1b), C6H5 (1c), CH2C6H4(p-CH3) (1d)) with 1,3-diiminoisoindoline 2 gives access to the corresponding symmetrical (1,3,5,7,9-pentaazanona-1,3,6,8-tetraenato) platinum(II) complexes [PtCl{NH=C(R)N=C(C6H4)NC=NC(R)=NH}] 3a-d, in good yields (65–77%). The compounds 3a-d have been characterized by IR, 1H, 13C and DEPT-135 NMR spectroscopies, ESI-MS and elemental analyses. GIAO/DFT studies have been performed to confirm the molecular structure of the platinum(II)-pincer 3d by comparing the experimental and theoretical 1H and 13C NMR chemical shifts, and it has shown good correlations between experimental and calculated chemical shifts for proton and carbon with correlation coefficients of 0.9947 and 0.9968, respectively. Molecular electrostatic potential is used to investigate the nucleophilic or electrophilic regions in the molecule 3d. The antimicrobial activities of compounds 3a-d are determined against different bacterial pathogens and yeasts. No toxicity is recorded against Artemia saline as a test organism for 3a-c, while moderate toxicity is found for 3d at 0.62 µM. Comparable antitumor activities are found for 3a-d against human colon HCT116 and human breast (MCF-7) cancer cell lines. The complexes 3a-d have shown good binding affinities to ct-DNA in the range of 6.00´105 to 8.33´105 and the conducted molecular docking studies suggest an intercalation mode of binding with DNA by the isoindole fragment of the ligands. Overall, this class of tridentate ligands have shown good potential in designing platinum(II) complexes with promising biological and anticancer activities. Moreover, the presence of the side chains on the ligands provides great design flexibility by introducing some chemical and/or physical characteristics