Photon beam relative dose validation of the DPM Monte Carlo code in lung‐equivalent media

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134925/1/mp5671.pd

The CORONIS Trial. International study of caesarean section surgical techniques: A randomised fractional, factorial trial

Background: Caesarean section is one of the most commonly performed operations on women throughout the world. Rates have increased in recent years – about 20–25% in many developed countries. Rates in other parts of the world vary widely. A variety of surgical techniques for all elements of the caesarean section operation are in use. Many have not yet been rigorously evaluated in randomised controlled trials, and it is not known whether any are associated with better outcomes for women and babies. Because huge numbers of women undergo caesarean section, even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women, and significant cost savings. Design: CORONIS is a multicentre, fractional, factorial randomised controlled trial and will be conducted in centres in Argentina, Ghana, India, Kenya, Pakistan and Sudan. Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision. Five comparisons will be carried out in one trial, using a 2 × 2 × 2 × 2 × 2 fractional factorial design. This design has rarely been used, but is appropriate for the evaluation of several procedures which will be used together in clinical practice. The interventions are: • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum (pelvic and parietal) • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity (one or more of the following: antibiotic use for maternal febrile morbidity during postnatal hospital stay, antibiotic use for endometritis, wound infection or peritonitis) or further operative procedures; or blood transfusion. The sample size required is 15,000 women in total; at least 7,586 women in each comparison. Discussion: Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries, because the rates of postoperative morbidity in these countries tend to be higher. More women could therefore benefit from improvements in techniques. Trial registration: The CORONIS Trial is registered in the Current Controlled Trials registry. ISCRTN31089967

Phenolic Profile, Nutritional Composition, Functional Properties and Antioxidant Activity of Newly Grown Parthenocarpic and Normal Seeded Tomato

The aim of the study was to compare the physico-chemical parameters, sugar, vitamin C, and phenolic profiles in five genotypes of local indeterminate tunnel tomato hybrid (LITTH) (LITTH-778, LITTH-784, LITTH-786, LITTH-788 and LITTH-790) of natural parthenocarpic tomato (NPT) and normal seeded tomato (NST). Samples were collected from the experimental fields of Ayub Agricultural Research Institute, Faisalabad, Pakistan. Physical parameters (fruit shape, fruit weight, fruit length, fruit width, number of seeds per fruit, shelf life), chemical composition (moisture, ash, crude fat, crude fibre, total carbohydrate, crude protein, vitamin C), ofNPT and NST were analyzed by reported methods. The methanolic extracts of tomato pulp were prepared by shaking and extracts were assayed for antioxidant activity. Sugars contents and phenolic profile of NPT and NST were estimatedusing HPLC method.Weight and size of NPT were less and smaller than the NST. Moreover, NPT were seedless with longer shelf-life and had more phenolic and flavonoid contents than the NST.HPLC analysis revealed that chlorogenic acid, gallic acid, p-coumeric acid were major phenolics in methanol (polar solvent) extracts of NST whereas, caffeic acid, gallic acid, p-coumeric acid in NPT extract.NPT contained higher concentration of sugar contents, but lower concentration of vitamin C than NST. In 2,2-diphenyl-1-picrylhydrazyl(DPPH) free-radical-scavenging assay, NPT fruits extracts showed high scavenging activity with the 50% inhibitory concentration (IC50)value of 22.56 µg/mL than NSTfruit extracts having IC50 29.49 µg/mL. This study provided useful information for farmers and nutritionists

Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y

A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 μg/mL and 1-12 μg/mL with limits of detection of 0.1 μg/mL and 0.3 μg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets

Involvement of bcl-2 and p21waf1 proteins in response of human breast cancer cell clones to Tomudex

Mechanisms of resistance to Tomudex include increased thymidylate synthase activity, as well as reduced intracellular drug uptake and polyglutamation. However, little is known about other mechanisms of resistance, such as a possible protection against Tomudex-induced apoptosis mediated by bcl-2. We transfected the MDA-MB-435 human breast cancer cell line, which is characterized by a mutated p53 gene, with cDNA of the bcl-2 gene and generated two clones (MDA-bcl4 and MDA-bcl7) characterized by bcl-2 expression twofold and fourfold that observed in the control cell clone (MDAneo). A concomitant overexpression of p21wafl was also detected in the MDA-bcl7 clone. The MDA-bcl4 clone was three times more resistant to a 24-h Tomudex exposure than the MDAneo clone, whereas the MDA-bcl7 clone was as sensitive to Tomudex as the control cell clone. A lower sensitivity of the MDA-bcl4 clone than MDAneo and MDA-bcl7 clones to 5-fluorouracil and gemcitabine was also observed. No significant difference was noted in the susceptibility of clones to fludarabine and methothrexate. Basal levels of thymidylate synthase activity were superimposable in the three clones. Tomudex induced a marked accumulation of cells in the S phase in all the clones. However, an apoptotic hypodiploid DNA peak and the characteristic nuclear morphology of apoptosis were observed only in the MDA-bcl7 clone after exposure to Tomudex. No difference in the treatment-induced modulation of proteins involved in cell cycle progression (cyclin A, cdk2, pRB, E2F-1) and apoptosis (bcl-2, bax) was observed in the three clones. The only exception was that the expression of p21wafl in the MDA-bcl4 clone was inducible at a Tomudex concentration much higher than that required to induce the protein in the other clones. Overall, the results indicate that bcl-2 and p21wafl proteins concur in determining the cellular profile of sensitivity/resistance to Tomudex. © 1999 Cancer Research Campaig

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

<p>Abstract</p> <p>Background</p> <p>The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression.</p> <p>Methods</p> <p>First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays.</p> <p>Results</p> <p>NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group.</p> <p>Conclusion</p> <p>(1) A single dose of 25 mg/kg body weight NNK by intratracheal instillation is sufficient to induce preneoplastic lesions in Wistar rat lungs. (2) COX-2 takes part in NNK-induced tumorigenesis but is not involved in proliferation. (3) Aspirin and PEITC have protective effects in the early stages of tumor progression initiated by NNK.</p

EGFR Kinase Promotes Acquisition of Stem Cell-Like Properties: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma Stem Cells

Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of “stemness” in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC