Antioxidant, Radical Scavenging and Antimicrobial Activities of Red Onion (Allium cepa L) Skin and Edible Part Extracts

The antioxidant, radical scavenging and antimicrobial activities of extracts from skin and edible part of red onion have been investigated. Crude extracts of red onion were obtained separately with acetone, ethanol and mixtures of solvents with water. The amounts of isolated phenolic compounds and quercetin from onion skin were approximately 3 to 5 times higher as from the onion edible part. Antioxidant and radical scavenging activities of onion skin extracts were generally high, results were comparable to that of BHT. Extracts from onion edible part showed somewhat lower activity. Furthermore, high activity of skin extracts against bacteria Escherichia coli, Pseudomonas fluorescens and Bacillus cereus and fungi Aspergillus niger, Trichoderma viride and Penicillium cyclopium was observed. Antimicrobial activity of edible part extracts against tested microorganisms is generally lower, while for Escherichia coli no growth inhibition was observed

Predictors of Radiotherapy Induced Bone Injury (RIBI) after stereotactic lung radiotherapy

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy.</p> <p>Methods</p> <p>Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created.</p> <p>Results</p> <p>46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 – 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 – 40 m). The mean maximum point dose in non-fractured ribs (n = 1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n = 41) 48.5 Gy ± 24.3 Gy (p < 0.0001). On univariate analysis, age, dose to 0.5 cc of the ribs (D_0.5), and the volume of the rib receiving at least 25 Gy (V₂₅), were significantly associated with RIBI. As D_0.5 and V₂₅ were cross-correlated (Spearman correlation coefficient: 0.57, p < 0.001), we selected D_0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 – 1.21, p = 0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 – 11.68, p = 0.003), and rib D_0.5 (odds ratio: 1.0009, 95% CI: 1.0007 – 1.001, p < 0.0001) were significantly associated with rib fracture.</p> <p>Using D_0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D_0.5 of 60 Gy.</p> <p>Conclusions</p> <p>Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D_0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.</p

Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust.

Objective: To further evaluate the higher-order measurement structure of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) questionnaire, with the aim of generating a summary score. Study design and setting: Using pretreatment QLQ-C30 data (N=3,282), we conducted confirmatory factor analyses to test seven previously evaluated higher-order models. We compared the summary score(s) derived from the best performing higher-order model with the original QLQ-C30 scale scores, using tumor stage, performance status and change over time (N=244) as grouping variables. Results: Whereas all models showed acceptable fit, we continued in the interest of parsimony with known-groups validity and responsiveness analyses using a summary score derived from the single higher-order factor model. The validity and responsiveness of this QLQ-C30 Summary Score was equal to, and in many cases superior to the original, underlying QLQ-C30 scale scores. Conclusion: Our results provide empirical support for a measurement model for the QLQ-C30 yielding a single summary score. The availability of this Summary Score can avoid problems with potential Type I errors that arise due to multiple testing when making comparisons based on the 15 outcomes generated by this questionnaire, and may reduce sample size requirements for HRQL studies using the QLQ-C30 questionnaire when an overall summary score is a relevant primary outcome

Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI.</p> <p>Case presentation</p> <p>Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib.</p> <p>Conclusion</p> <p>NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.</p

Enhancing treatment decision-making: pilot study of a treatment decision aid in stage IV non-small cell lung cancer

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37–77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language. Most had received chemotherapy, with 65% currently on treatment. Patients were not anxious at baseline and had clear understanding of the goals and toxicity of chemotherapy in advanced NSCLC. After reviewing the DA, patients' anxiety decreased slightly (P=0.04) and knowledge scores improved by 25% (P<0.001). Most improvements in understanding were of prognosis with and without chemotherapy, although patients still believed advanced NSCLC to be curable. Patients rated the DA highly with respect to information clarity, usefulness and were positive about its use in practice, although 40% found the prognostic information slightly upsetting. The DA for advanced NSCLC is feasible, acceptable to patients and improves understanding of advanced NSCLC without increasing patient anxiety

High levels of untreated distress and fatigue in cancer patients

The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkins lymphoma

A B S T R A C T Purpose We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin&apos;s lymphoma. Patients and Methods Patients with nonbulky clinical stage I to IIA Hodgkin&apos;s lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. Results We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P ϭ .006; 93% v 87%); no differences in event-free survival (P ϭ .06; 88% v 86%) or overall survival (P ϭ .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P ϭ .004; 95% v 88%); no difference in overall survival was detected (P ϭ .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin&apos;s lymphoma or acute treatment-related toxicity. Conclusion In patients with limited-stage Hodgkin&apos;s lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin&apos;s lymphoma or acute treatment-related toxicity

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. We used everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to EGFR inhibitors, both in vitro and in vivo. We demonstrated that everolimus is active against EGFR-resistant cancer cell lines and partially restores the ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the expression of EGFR-related signalling effectors and VEGF production, inhibiting proliferation and capillary tube formation of endothelial cells, both alone and in combination with gefitinib. Finally, combination of everolimus and gefitinib inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts, activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with everolimus overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment