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  1. Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial

    PubMed Central

    Yuste Sánchez, María José; Zapico Goñi, Álvaro; Prieto Merino, David; Mayoral del Moral, Orlando; Cerezo Téllez, Ester; Minayo Mogollón, Elena

    2010-01-01

    Objective To determine the effectiveness of early physiotherapy in reducing the risk of secondary lymphoedema after surgery for breast cancer. Design Randomised, single blinded, clinical trial. Setting University hospital in Alcalá de Henares, Madrid, Spain. Participants 120 women who had breast surgery involving dissection of axillary lymph nodes between May 2005 and June 2007. Intervention The early physiotherapy group was treated by a physiotherapist with a physiotherapy programme including manual lymph drainage, massage of scar tissue, and progressive active and action assisted shoulder exercises. This group also received an educational strategy. The control group received the educational strategy only. Main outcome measure Incidence of clinically significant secondary lymphoedema (>2 cm increase in arm circumference measured at two adjacent points compared with the non-affected arm). Results 116 women completed the one year follow-up. Of these, 18 developed secondary lymphoedema (16%): 14 in the control group (25%) and four in the intervention group (7%). The difference was significant (P=0.01); risk ratio 0.28 (95% confidence interval 0.10 to 0.79). A survival analysis showed a significant difference, with secondary lymphoedema being diagnosed four times earlier in the control group than in the intervention group (intervention/control, hazard ratio 0.26, 95% confidence interval 0.09 to 0.79). Conclusion Early physiotherapy could be an effective intervention in the prevention of secondary lymphoedema in women for at least one year after surgery for breast cancer involving dissection of axillary lymph nodes. Trial registration Current controlled trials ISRCTN95870846. PMID:20068255

  2. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients. PMID:1834291

  3. Volunteers or victims: patients' views of randomised cancer clinical trials.

    PubMed Central

    Slevin, M.; Mossman, J.; Bowling, A.; Leonard, R.; Steward, W.; Harper, P.; McIllmurray, M.; Thatcher, N.

    1995-01-01

    Randomised clinical trials are essential for the objective evaluation of different treatment strategies in cancer. However, in the field of oncology, very few of the eligible patients are entered into trials, and most treatments have only been tested on a small percentage of patients. For doctors, a major deterrent to participating in trials is the lack of resources--particularly time, but often also the local facilities. This report suggests that patients themselves are willing to take part in clinical research, and are attracted by being treated by a doctor with a specialist interest in the disease and encouraged by the possibility that their progress will be monitored closely. With the recent NHS changes, it is timely for the Department of Health and other national health departments to consider carefully what can be done to ensure that no new treatments are adopted without effective evaluation. This will require departments of health to identify and implement ways to facilitate accrual of appropriate numbers of patients onto research protocols (whether non-randomised phase I or phase II studies or large, multicentre phase III trials) over short time periods. PMID:7779722

  4. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Munro, A. J.

    1995-01-01

    Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer. PMID:7819055

  5. Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial

    PubMed Central

    Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst

    2012-01-01

    Objective To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. Method The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. Results There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales ‘anxiety’, ‘behaviour’, ‘dejection’, ‘self-blame’, ‘focus on airway symptoms’ and ‘introvert’, with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Conclusions Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants—both the participants in the screen group and the control group. This negative impact was greatest for the control group. PMID:22382119

  6. Single dose vitamin A treatment in acute shigellosis in Bangladesh children: randomised double blind controlled trial.

    PubMed Central

    Hossain, S.; Biswas, R.; Kabir, I.; Sarker, S.; Dibley, M.; Fuchs, G.; Mahalanabis, D.

    1998-01-01

    OBJECTIVE: To evaluate the efficacy of a single large oral dose of vitamin A in treating acute shigellosis in children in Bangladesh. DESIGN: Randomised double blind controlled clinical trial. SETTING: Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 83 children aged 1-7 years with bacteriologically proved shigellosis but no clinical signs of vitamin A deficiency; 42 were randomised to treatment with vitamin A and 41 formed a control group. INTERVENTION: Children were given a single oral dose of 200,000 IU of vitamin A plus 25 IU vitamin E or a control preparation of 25 IU vitamin E. MAIN OUTCOME MEASURES: Clinical cure on study day 5 and bacteriological cure. RESULTS: Baseline characteristics of the subjects in the two treatment groups were similar. Significantly more children in the vitamin A group than in the control group achieved clinical cure (19/42 (45%) v 8/14 (20%); chi 2 = 5.14, 1 df, P = 0.02; risk ratio = 0.68 (95% confidence interval; 0.50 to 0.93)). When cure was determined bacteriologically, the groups had similar rates (16/42 (38%) v 16/41 (39%); chi 2 = 0.02, 1 df, P = 0.89; risk ratio = 0.98 (0.70 to 1.39)). CONCLUSIONS: Vitamin A reduces the severity of acute shigellosis in children living in areas where vitamin A deficiency is a major public health problem. PMID:9492664

  7. Advance care planning in patients with incurable cancer: study protocol for a randomised controlled trial

    PubMed Central

    Clayton, Josephine; Butow, Phyllis N; Silvester, William; Detering, Karen; Hall, Jane; Kiely, Belinda E; Cebon, Jonathon; Clarke, Stephen; Bell, Melanie L; Stockler, Martin; Beale, Phillip; Tattersall, Martin H N

    2016-01-01

    Introduction There is limited evidence documenting the effectiveness of Advance Care Planning (ACP) in cancer care. The present randomised trial is designed to evaluate whether the administration of formal ACP improves compliance with patients' end-of-life (EOL) wishes and patient and family satisfaction with care. Methods and analysis A randomised control trial in eight oncology centres across New South Wales and Victoria, Australia, is designed to assess the efficacy of a formal ACP intervention for patients with cancer. Patients with incurable cancer and an expected survival of 3–12 months, plus a nominated family member or friend will be randomised to receive either standard care or standard care plus a formal ACP intervention. The project sample size is 210 patient–family/friend dyads. The primary outcome measure is family/friend-reported: (1) discussion with the patient about their EOL wishes and (2) perception that the patient's EOL wishes were met. Secondary outcome measures include: documentation of and compliance with patient preferences for medical intervention at the EOL; the family/friend's perception of the quality of the patient's EOL care; the impact of death on surviving family; patient–family and patient–healthcare provider communication about EOL care; patient and family/friend satisfaction with care; quality of life of patient and family/friend subsequent to trial entry, the patient's strength of preferences for quality of life and length of life; the costs of care subsequent to trial entry and place of death. Ethics and dissemination Ethical approval was received from the Sydney Local Health District (RPA Zone) Human Research Ethical Committee, Australia (Protocol number X13-0064). Study results will be submitted for publication in peer-reviewed journals and presented at national and international conferences. Trial registration number Pre-results; ACTRN12613001288718. PMID:27909034

  8. Beating the blues after Cancer: randomised controlled trial of a tele-based psychological intervention for high distress patients and carers

    PubMed Central

    2009-01-01

    Background The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention. Methods/design 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life. Discussion The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers. Trial Registration ACTRN12609000301268. PMID:19531265

  9. Clinical outcomes of Single-Visit oral Prophylaxis: A practice-based randomised controlled trial

    PubMed Central

    2011-01-01

    Background Practice-based general dental practitioners routinely provide "scale and polish" or "oral prophylaxis" to patients attending their practices. Despite its routine provision, there is no evidence to support the clinical effectiveness of single-visit scale and polish, nor the frequency at which it should be provided. A recent systematic review recommended that future trials investigating scale and polish should involve dental practice patients. Methods A practice-based parallel randomised controlled trial with 24-month follow-up was conducted. Healthy adults (Basic Periodontal Examination [BPE] codes <3) were randomly assigned to 3 groups (6-month, 12-month, or 24-month interval between scale and polish). The primary outcome was gingival bleeding with the hypothesis that 6-monthly scale and polish would result in lower prevalence than 12-month or 24-month frequency. Follow-up measurements were recorded by examiners blinded to the allocation. 125, 122 and 122 participants were randomised to the 6-month, 12-month and 24-month groups respectively. Complete data set analyses were conducted for 307 participants: 107, 100, and 100 in the 6-month, 12-month and 24-month groups respectively. Chi-square test and ANOVA were used to compare treatment groups at follow-up. Logistic regression and ANCOVA were used to estimate the relationship between outcome and treatment group, adjusted for baseline values. Multiple imputation analyses were also carried out for participants with incomplete data sets. Results Prevalence of gingival bleeding at follow-up was 78.5% (6-month), 78% (12-month) and 82% (24-month) (p = 0.746). There were no statistically significant differences between groups with respect to follow-up prevalence of plaque and calculus. Statistically significant differences detected in the amount (millimetres) of calculus were too small to be clinically significant. Seventeen (4.6%) participants were withdrawn from the trial to receive additional treatment

  10. Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer

    PubMed Central

    Murray, Sonya R; Murchie, Peter; Campbell, Neil; Walter, Fiona M; Mazza, Danielle; Habgood, Emily; Kutzer, Yvonne; Martin, Andrew; Goodall, Stephen; Barnes, David J

    2015-01-01

    Introduction Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer. Methods/analysis The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms. Ethics and dissemination Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016. Trial

  11. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis

    PubMed Central

    Maggioni, A; Benedetti Panici, P; Dell'Anna, T; Landoni, F; Lissoni, A; Pellegrino, A; Rossi, R S; Chiari, S; Campagnutta, E; Greggi, S; Angioli, R; Manci, N; Calcagno, M; Scambia, G; Fossati, R; Floriani, I; Torri, V; Grassi, R; Mangioni, C

    2006-01-01

    No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46–1.21, P=0.16) and death (HR=0.85, 95%CI=0.49–1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=–3.4–14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=−7.0–9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival. PMID:16940979

  12. Anticipated regret to increase uptake of colorectal cancer screening (ARTICS): A randomised controlled trial

    PubMed Central

    O'Carroll, Ronan E.; Chambers, Julie A.; Brownlee, Linda; Libby, Gillian; Steele, Robert J.C.

    2015-01-01

    Screening is important for early detection of colorectal cancer. Our aim was to determine whether a simple anticipated regret (AR) intervention could increase uptake of colorectal cancer screening. A randomised controlled trial of a simple, questionnaire-based AR intervention, delivered alongside existing pre-notification letters, was conducted. A total of 60,000 adults aged 50–74 years from the Scottish National Screening programme were randomised into the following groups: (1) no questionnaire (control), (2) Health Locus of Control questionnaire (HLOC) or (3) HLOC plus AR questionnaire. The primary outcome was return of the guaiac faecal occult blood test (FOBT). The secondary outcomes included intention to return test kit and perceived disgust (ICK). A total of 59,366 people were analysed as allocated (intention-to-treat (ITT)); no overall differences were seen between the treatment groups on FOBT uptake (control: 57.3%, HLOC: 56.9%, AR: 57.4%). In total, 13,645 (34.2%) individuals returned the questionnaires. Analysis of the secondary questionnaire measures showed that AR indirectly affected FOBT uptake via intention, whilst ICK directly affected FOBT uptake over and above intention. The effect of AR on FOBT uptake was also moderated by intention strength: for less-than-strong intenders only, uptake was 4.2% higher in the AR (84.6%) versus the HLOC group (80.4%) (95% CI for difference (2.0, 6.5)). The findings show that psychological concepts including AR and perceived disgust (ICK) are important factors in determining FOBT uptake. However, the AR intervention had no simple effect in the ITT analysis. It can be concluded that, in those with low intentions, exposure to AR may be required to increase FOBT uptake. The current controlled trials are presented at the website www.controlled-trials.com (number: ISRCTN74986452). PMID:26301484

  13. Conductive Education as a Method of Stroke Rehabilitation: A Single Blinded Randomised Controlled Feasibility Study

    PubMed Central

    Jutley-Neilson, Jagjeet; Russell, Nicholas C. C.; Sackley, Catherine M.

    2016-01-01

    Background. Conductive Education for stroke survivors has shown promise but randomised evidence is unavailable. This study assessed the feasibility of a definitive randomised controlled trial to evaluate efficacy. Methods. Adult stroke survivors were recruited through local community notices. Those completing the baseline assessment were randomised using an online program and group allocation was independent. Intervention group participants received 10 weekly 1.5-hour sessions of Conductive Education at the National Institute of Conductive Education in Birmingham, UK. The control group participants attended two group meetings. The study evaluated the feasibility of recruitment procedures, delivery of the intervention, retention of participants, and appropriateness of outcome measures and data collection methods. Independent assessments included the Barthel Index, the Stroke Impact Scale, the Timed Up and Go test, and the Hospital Anxiety and Depression Scale. Results. Eighty-two patients were enrolled; 77 completed the baseline assessment (46 men, mean age 62.1 yrs.) and were randomised. 70 commenced the intervention (n = 37) or an equivalent waiting period (n = 33). 32/37 completed the 10-week training and 32/33 the waiting period. There were no missing items from completed questionnaires and no adverse events. Discussion. Recruitment, intervention, and assessment methods worked well. Transport issues for intervention and assessment appointments require review. Conclusion. A definitive trial is feasible. This trial is registered with ISRCTN84064492. PMID:27418997

  14. A randomised controlled trial of nurse-managed trial conclusion following early phase cancer trial participation.

    PubMed

    Cox, K; Wilson, E; Arthur, A; Elkan, R; Armstrong, S

    2005-07-11

    The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial.

  15. Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR)

    PubMed Central

    Thorne, Kymberley; Hutchings, Hayley; Islam, Saiful; Holland, Gail; Hatcher, Olivia; Gwynne, Sarah; Jenkins, Ian; Coyne, Peter; Duff, Michael; Feldman, Melanie; Winter, Des C; Gollins, Simon; Quirke, Phil; West, Nick; Brown, Gina; Fitzsimmons, Deborah; Brown, Alan; Beynon, John

    2016-01-01

    Introduction There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity. Methods and analysis This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8–12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up. Objectives Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored. Ethics and dissemination The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review

  16. Meeting the support and information needs of women with advanced breast cancer: a randomised controlled trial

    PubMed Central

    Aranda, S; Schofield, P; Weih, L; Milne, D; Yates, P; Faulkner, R

    2006-01-01

    Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer. This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Australia. One hundred and five women with advanced breast cancer were recruited and randomised to receive the intervention or usual care, then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version (2.0) (EORTC Q-C30) (version 2) and Supportive Care Needs Survey (SCNS) at 1 month and 3 months postrecruitment. No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores. However, when the groups were divided into high needs (score of above 50) and low baseline needs (score of 50 or below) for each SCNS subscale, a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs. In conclusions, this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs. There was no evidence of the intervention influencing the quality of life; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains. Possibly, the intervention was not sufficiently intense to achieve an effect. PMID:16967054

  17. A randomised controlled pilot feasibility study of the physical and psychological effects of an integrated support programme in breast cancer.

    PubMed

    Baker, Barbara S; Harrington, Julia E; Choi, Beak-San; Kropf, Pascale; Muller, Ingrid; Hoffman, Caroline J

    2012-08-01

    A pilot study was conducted to assess recruitment and effectiveness of an integrated support programme in women with breast cancer. Twelve participants were randomised to receive medical care with or without the support programme. Psychosocial questionnaires and immune/hormonal assays were completed at baseline, three and six months. Recruitment was problematic. In the intervention group, mental fatigue was significantly improved (p = 0.016) compared to controls; increased NK cell activity suggested an improvement in immune function. Total stress (p = 0.009), anxiety (p = 0.032) and endocrine-specific (p = 0.032) symptoms were significantly improved in the controls. A large-scale randomisation trial appears warranted, dependent upon effective recruitment.

  18. Efficacy of communication skills training on colorectal cancer screening by GPs: a cluster randomised controlled trial.

    PubMed

    Aubin-Auger, I; Laouénan, C; Le Bel, J; Mercier, A; Baruch, D; Lebeau, J P; Youssefian, A; Le Trung, T; Peremans, L; Van Royen, P

    2016-01-01

    Colorectal cancer (CRC) mass screening has been implemented in France since 2008. Participation rates remain too low. The objective of this study was to test if the implementation of a training course focused on communication skills among general practitioners (GP) would increase the delivery of gaiac faecal occult blood test and CRC screening participation among the target population of each participating GP. A cluster randomised controlled trial was conducted with GP's practice as a cluster unit. GPs from practices in the control group were asked to continue their usual care. GPs of the intervention group received a 4-h educational training, built with previous qualitative data on CRC screening focusing on doctor-patient communication with a follow-up of 7 months for both groups. The primary outcome measure was the patients' participation rate in the target population for each GP. Seventeen GPs (16 practices) in intervention group and 28 GPs (19 practices) in control group participated. The patients' participation rate in the intervention group were 36.7% vs. 24.5% in the control group (P = 0.03). Doctor-patient communication should be developed and appear to be one of the possible targets of improvement patients adherence and participation rate in the target population for CRC mass screening.

  19. The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol

    PubMed Central

    2012-01-01

    Background People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied. Methods/design A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels. Discussion This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible. Trial registration Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235 PMID:23216897

  20. Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial

    PubMed Central

    Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alström, Katarina; Andersson, Gerhard; Ljótsson, Brjánn; Rück, Christian

    2016-01-01

    Objectives To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. Design A 12 week single blind parallel group randomised controlled trial. Setting Academic medical centre. Participants 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. Interventions Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. Main outcome measures The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a ≥30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. Results BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference −7.1 points, 95% confidence interval −9.8 to −4.4), depression (MADRS-S group difference −4.5 points, −7.5 to −1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self

  1. Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised clinical trial

    PubMed Central

    Dell' Anna, T; Signorelli, M; Benedetti-Panici, P; Maggioni, A; Fossati, R; Fruscio, R; Milani, R; Bocciolone, L; Buda, A; Mangioni, C; Scambia, G; Angioli, R; Campagnutta, E; Grassi, R; Landoni, F

    2012-01-01

    Background: The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies. Methods: From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA–IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS). Results: The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87–1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8% HR for death=1.04, 95% CI=0.733–1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively). Conclusion: SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS. PMID:22864456

  2. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

    PubMed Central

    Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

    2016-01-01

    Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

  3. Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study

    PubMed Central

    De Placido, S; Lopez, M; Carlomagno, C; Paoletti, G; Palazzo, S; Manzione, L; Iannace, C; Ianniello, G P; De Vita, F; Ficorella, C; Farris, A; Pistillucci, G; Gemini, M; Cortesi, E; Adamo, V; Gebbia, N; Palmeri, S; Gallo, C; Perrone, F; Persico, G; Bianco, A R

    2005-01-01

    The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2 × 2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73–1.09) for patients receiving FA and 0.99 (95% CI 0.80–1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80–1.30) and 0.94 (95% CI 0.73–1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients. PMID:16222322

  4. Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer

    PubMed Central

    Jarvis, David; Mitchell, Jonathan S; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Meklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Win, Aung K; Hopper, John L; Jenkins, Mark A; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Aaltonen, Lauri A; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Houlston, Richard S

    2016-01-01

    Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC. Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls. Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02–1.49, P=0.033), 1.59 (95% CI: 1.08–2.34, P=0.019) and 1.07 (95% CI: 1.03–1.13, P=0.018), respectively. There was no evidence for association between birth weight and CRC (OR=1.22, 95% CI: 0.89–1.67, P=0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10–1.44, P=7.7 × 10−4) and 1.40 (95% CI: 1.14–1.72, P=1.2 × 10−3), respectively. Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity. PMID:27336604

  5. Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study.

    PubMed

    Brunner, Clair; Davies, Neil M; Martin, Richard M; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Donovan, Jenny; Hamdy, Freddie C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Zuccolo, Luisa

    2017-01-01

    Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed  = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed  = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

  6. Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised, double blind, multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition.

    PubMed Central

    1991-01-01

    OBJECTIVE--To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. DESIGN--Prospective, randomised, double blind, parallel group, multicentre study. SETTING--University of hospital departments of obstetrics and gynaecology in different European countries. SUBJECTS--272 puerperal women not wishing to lactate (136 randomised to each drug). INTERVENTIONS--Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. MAIN OUTCOME MEASURES--Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. RESULTS--Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. CONCLUSION--A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition. PMID:1676318

  7. Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

    PubMed Central

    Brunner, Clair; Davies, Neil M.; Martin, Richard M.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Donovan, Jenny; Hamdy, Freddie C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev

    2016-01-01

    Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression. PMID:27643404

  8. A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol

    PubMed Central

    Langley, Ruth E.; Kynaston, Howard G.; Alhasso, Abdulla A.; Duong, Trinh; Paez, Edgar M.; Jovic, Gordana; Scrase, Christopher D.; Robertson, Andrew; Cafferty, Fay; Welland, Andrew; Carpenter, Robin; Honeyfield, Lesley; Abel, Richard L.; Stone, Michael; Parmar, Mahesh K.B.; Abel, Paul D.

    2016-01-01

    Background Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. Objective To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). Design, setting, and participants Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006–2011; 1:1, thereafter) were recruited into a BMD study (2006–2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. Interventions LHRHa as per local practice, OP (FemSeven 100 μg/24 h patches). Outcome measurements and statistical analysis The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. Results and limitations A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was −0.021 g/cm3 for patients randomised to the LHRHa arm (mean percentage change −1.4%) and +0.069 g/cm3 for the OP arm (+6.0%; p < 0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa −3.0% and OP +7.9% (p < 0.001). Conclusions Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial. Patient summary This study found that prostate cancer patients treated with transdermal oestradiol

  9. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial

    PubMed Central

    Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John MS; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

    2009-01-01

    Summary Background Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. Methods In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2 at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m2 at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m2 at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. Findings All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0·95, 95% CI 0·85–1·08; p=0·44). 75·6% (95% CI 73·7–77·5) of patients in the experimental group and 74·3% (72·3–76·2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0·0001); the most frequent events were neutropenia (937 events vs 797 events

  10. Sipjeondaebo-tang in patients with cancer with anorexia: a protocol for a pilot, randomised, controlled trial

    PubMed Central

    Cheon, Chunhoo; Park, Sunju; Park, Yu Lee; Huang, Ching-Wen; Ko, Youme; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

    2016-01-01

    Introduction Cancer-related anorexia is the loss of appetite or desire to eat in patients with cancer. Although treatments for cancer-related anorexia do exist, patients have sought complementary and alternative medicine including herbal remedies, due to safety concerns. Sipjeondaebo-tang is one among other popular herbal medicines that are beneficial to management of anorexia in Korea. The purpose of this study is to examine the feasibility for a full randomised clinical trial of Sipjeondaebo-tang for cancer-related anorexia. Methods and analysis This study is a randomised, double-blinded and placebo-controlled trial of Sipjeondaebo-tang. For the study, 40 patients with cancer, aged 20–80 years, who reported anorexia, will be recruited. The participants will receive either 3 g of Sipjeondaebo-tang or a placebo, 3 times a day for 4 weeks. The primary end point is a change in the anorexia/cachexia subscale (A/CS) of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary end points include changes in the visual analogue scale (VAS) of appetite, cortisol and ghrelin. The outcomes will be measured on every visit. Each participant will visit once a week during 4 weeks. Ethics and dissemination The present study has been approved by the Institutional Review Board of the Dunsan Korean Medicine Hospital of Daejeon University (reference DJDSKH-15-03-2 (V.2.0)). The results will be disseminated in a peer-reviewed journal and scientific conference. Trial registration number NCT02468141; Pre-results. PMID:27173813

  11. Chiropractic spinal manipulative therapy for migraine: a study protocol of a single-blinded placebo-controlled randomised clinical trial

    PubMed Central

    Chaibi, Aleksander; Šaltytė Benth, Jūratė; Tuchin, Peter J; Russell, Michael Bjørn

    2015-01-01

    Introduction Migraine affects 15% of the population, and has substantial health and socioeconomic costs. Pharmacological management is first-line treatment. However, acute and/or prophylactic medicine might not be tolerated due to side effects or contraindications. Thus, we aim to assess the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraineurs in a single-blinded placebo-controlled randomised clinical trial (RCT). Method and analysis According to the power calculations, 90 participants are needed in the RCT. Participants will be randomised into one of three groups: CSMT, placebo (sham manipulation) and control (usual non-manual management). The RCT consists of three stages: 1 month run-in, 3 months intervention and follow-up analyses at the end of the intervention and 3, 6 and 12 months. The primary end point is migraine frequency, while migraine duration, migraine intensity, headache index (frequency x duration x intensity) and medicine consumption are secondary end points. Primary analysis will assess a change in migraine frequency from baseline to the end of the intervention and follow-up, where the groups CSMT and placebo and CSMT and control will be compared. Owing to two group comparisons, p values below 0.025 will be considered statistically significant. For all secondary end points and analyses, a p value below 0.05 will be used. The results will be presented with the corresponding p values and 95% CIs. Ethics and dissemination The RCT will follow the clinical trial guidelines from the International Headache Society. The Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services have approved the project. Procedure will be conducted according to the declaration of Helsinki. The results will be published at scientific meetings and in peer-reviewed journals. Trial registration number NCT01741714. PMID:26586317

  12. Electrochemical Genetic Profiling of Single Cancer Cells.

    PubMed

    Acero Sánchez, Josep Ll; Joda, Hamdi; Henry, Olivier Y F; Solnestam, Beata W; Kvastad, Linda; Akan, Pelin S; Lundeberg, Joakim; Laddach, Nadja; Ramakrishnan, Dheeraj; Riley, Ian; Schwind, Carmen; Latta, Daniel; O'Sullivan, Ciara K

    2017-03-21

    Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection. Cells were isolated using laser capture and lysed, and the mRNA was extracted and transcribed into DNA. Seven markers were amplified by MLPA, which allows for the simultaneous amplification of multiple targets with a single primer pair, using MLPA probes containing unique barcode sequences. Capture probes complementary to each of these barcode sequences were immobilized on a printed circuit board (PCB) manufactured electrode array and exposed to single-stranded MLPA products and subsequently to a single stranded DNA reporter probe bearing a HRP molecule, followed by substrate addition and fast electrochemical pulse amperometric detection. We present a simple, rapid, flexible, and inexpensive approach for the simultaneous quantification of multiple breast cancer related mRNA markers, with single tumor cell sensitivity.

  13. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.

    PubMed Central

    Field, John K; Duffy, Stephen W; Baldwin, David R; Brain, Kate E; Devaraj, Anand; Eisen, Tim; Green, Beverley A; Holemans, John A; Kavanagh, Terry; Kerr, Keith M; Ledson, Martin; Lifford, Kate J; McRonald, Fiona E; Nair, Arjun; Page, Richard D; Parmar, Mahesh Kb; Rintoul, Robert C; Screaton, Nicholas; Wald, Nicholas J; Weller, David; Whynes, David K; Williamson, Paula R; Yadegarfar, Ghasem; Hansell, David M

    2016-01-01

    BACKGROUND Lung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects. OBJECTIVES To (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening. DESIGN A pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years). SETTING Thoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire. PARTICIPANTS Individuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres. INTERVENTIONS A thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria. MAIN OUTCOME MEASURES Population-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling. RESULTS A total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in

  14. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial

    PubMed Central

    Quist, Morten; Andersen, Christina; Møller, Tom; Herrstedt, Jørn; Kronborg, Dorte; Baadsgaard, Marie T; Vistisen, Kirsten; Midtgaard, Julie; Christiansen, Birgitte; Stage, Maria; Kronborg, Morten T; Rørth, Mikael

    2009-01-01

    Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease. Design Randomised controlled trial. Setting Two university hospitals in Copenhagen, Denmark. Participants 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up. Intervention Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care. Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo2max). Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables. Results Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of −6.6 points (95% confidence interval −12.3 to −0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption

  15. Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: randomised trial

    PubMed Central

    Sundar, Shyam; Agrawal, G; Rai, Madhukar; Makharia, M K; Murray, Henry W

    2001-01-01

    Objective To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar). Design Randomised, open label study. Setting Inpatient unit for leishmaniasis in Bihar, India. Participants 91 adults and children with splenic aspirate positive for infection. Interventions Total dose of 5 mg/kg of liposomal amphotericin B given as a single infusion (n=46) or as once daily infusions of 1 mg/kg for five days (n=45). Main outcome measures Clinical and parasitological cure assessed 14 days after treatment and long term definitive cure (healthy, no relapse) at six months. Results All but one person in each group had an initial apparent cure. During six months of follow up, three patients in the single dose group and two in the five dose group relapsed. Complete response (definitive cure) was therefore achieved in 84 of 91 subjects (92%): 42 of 46 patients in the single dose group (91%, 95% confidence interval 79% to 98%) and 42 of 45 in the five dose group (93%, 82% to 99%). Response rates in the two groups were not significantly different. Conclusion Low dose liposomal amphotericin B (5 mg/kg), given either as a five day course or as a single infusion, seems to be effective for visceral leishmaniasis and warrants further testing. What is already known on this topicPentavalent antimony is now ineffective against visceral leishmaniasis in IndiaLiposomal amphotericin B is effective but high cost prohibits its use in developing countriesWhat this study addsLiposomal amphotericin B (5 mg/kg), given as a single infusion or five daily infusions of 1 mg/kg, cured 92% of patientsIf proved effective in larger trials, low dose regimens could make the drug more affordable PMID:11520836

  16. Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol

    PubMed Central

    Schünemann, Holger J; Ventresca, Matthew; Crowther, Mark; Briel, Matthias; Zhou, Qi; Garcia, David; Lyman, Gary; Noble, Simon; Macbeth, Fergus; Griffiths, Gareth; DiNisio, Marcello; Beyene, Joseph; Mbuagbaw, Lawrance; Neumann, Ignacio; Van Es, Nick; Brouwers, Melissa; Brozek, Jan; Guyatt, Gordon; Levine, Mark; Moll, Stephan; Santesso, Nancy; Streiff, Michael; Baldeh, Tejan; Florez, Ivan; Gurunlu Alma, Ozlem; Solh, Ziad; Ageno, Walter; Marcucci, Maura; Bozas, George; Zulian, Gilbert; Maraveyas, Anthony; Lebeau, Bernard; Buller, Harry; Evans, Jessica; McBane, Robert; Bleker, Suzanne; Pelzer, Uwe; Akl, Elie A

    2016-01-01

    Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline

  17. Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials

    PubMed Central

    Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

    2017-01-01

    Objective To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Setting Tertiary cancer referral hospitals in three state capital cities in Australia. Participants 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. Interventions We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Primary and secondary outcomes Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. Main outcome measure: scores on the Quality of Informed Consent questionnaire (QuIC). Results 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Conclusions Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Trial registration number Results, ACTRN

  18. Extended radical mastectomy versus simple mastectomy followed by radiotherapy in primary breast cancer. A fifty-year follow-up to the Copenhagen Breast Cancer randomised study.

    PubMed

    Johansen, Helge; Kaae, Sigvard; Jensen, Maj-Britt; Mouridsen, Henning T

    2008-01-01

    From November 1951 to December 1957, 666 consecutive patients with untreated primary breast cancer admitted to the Radium Center in Copenhagen were randomised before their operability was evaluated into two groups, simple mastectomy with postoperative radiotherapy or extended radical mastectomy. Following physical examination 241 of the patients were excluded, primarily due to tumours deemed inoperable due to clinical criteria (n =107) and due to poor general condition (n =69). Twenty-five years results of disease-free free survival and fifty years results of survival are presented, showing no difference between the two groups. Patients with clinical stage I did significantly better than patients with stage II-III tumours. Patients with grade I tumours had a better survival than patients with grade II-III. The breast cancer associated mortality was lower in premenopausal patients compared to postmenopausal patients. An excess mortality due to breast cancer was evident up to 20-25 years following the primary diagnosis.

  19. Using a randomised controlled trial (RCT) methodology in CAM research with gynaecological cancer patients: A commentary on the perks and pitfalls.

    PubMed

    Archer, Stephanie; Forshaw, Mark J

    2015-02-01

    This paper provides a commentary on several challenges faced by researchers when conducting randomised controlled trials (RCTs) utilising complementary therapies with cancer patients. Several factors, such as research design and recruitment to the intervention are discussed. Examples are drawn from an RCT conducted by the lead author regarding the use of yoga to improve the quality of life of gynaecological cancer patients undergoing treatment for their cancer. This paper gives methodological insights into some of the difficulties experienced when conducting research with cancer patients, and provides a number of recommendations based on the available evidence and practical application of these methods.

  20. A randomised controlled phase II trial of pre-operative celecoxib treatment reveals anti-tumour transcriptional response in primary breast cancer

    PubMed Central

    2013-01-01

    Introduction Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic breast cancer models, over-expression of COX-2 leads to tumour formation while COX-2 inhibition exerts anti-tumour effects in breast cancer cell lines. To further determine the effect of COX-2 inhibition in primary breast cancer, we aimed to identify transcriptional changes in breast cancer tissues of patients treated with the selective COX-2 inhibitor celecoxib. Methods In a single-centre double-blind phase II study, thirty-seven breast cancer patients were randomised to receive either pre-operative celecoxib (400 mg) twice daily for two to three weeks (n = 22) or a placebo according to the same schedule (n = 15). Gene expression in fresh-frozen pre-surgical biopsies (before treatment) and surgical excision specimens (after treatment) was profiled by using Affymetrix arrays. Differentially expressed genes and altered pathways were bioinformatically identified. Expression of selected genes was validated by quantitative PCR (qPCR). Immunohistochemical protein expression analyses of the proliferation marker Ki-67, the apoptosis marker cleaved caspase-3 and the neo-angiogenesis marker CD34 served to evaluate biological response. Results We identified 972 and 586 significantly up- and down-regulated genes, respectively, in celecoxib-treated specimens. Significant expression changes in six out of eight genes could be validated by qPCR. Pathway analyses revealed over-representation of deregulated genes in the networks of proliferation, cell cycle, extracellular matrix biology, and inflammatory immune response. The Ki-67 mean change relative to baseline was -29.1% (P = 0.019) and -8.2% (P = 0.384) in the treatment and control arm, respectively. Between treatment groups, the change in Ki-67 was statistically significant (P = 0.029). Cleaved caspase-3 and CD34 expression were not significantly different between the celecoxib-treated and placebo-treated groups

  1. Protocol for a pilot randomised controlled trial of an online intervention for post-treatment cancer survivors with persistent fatigue

    PubMed Central

    Corbett, Teresa; Walsh, Jane C; Groarke, AnnMarie; Moss-Morris, Rona; McGuire, Brian E

    2016-01-01

    Introduction Many post-treatment cancer survivors experience persistent fatigue that can disrupt attempts to resume normal everyday activities after treatment. Theoretical models that aim to explain contributory factors that initiate and sustain fatigue symptoms, or that influence the efficacy of interventions for cancer-related fatigue (CrF) require testing. Adjustment to fatigue is likely to be influenced by coping behaviours that are guided by the representations of the symptom. Objectives This paper describes the protocol for a pilot trial of a systematically and theoretically designed online intervention to enable self-management of CrF after cancer treatment. Methods and analysis This 2-armed randomised controlled pilot trial will study the feasibility and potential effectiveness of an online intervention. Participants will be allocated to either the online intervention (REFRESH (Recovery from Cancer-Related Fatigue)), or a leaflet comparator. Participants 80 post-treatment cancer survivors will be recruited for the study. Interventions An 8-week online intervention based on cognitive–behavioural therapy. Primary and secondary outcome measures The primary outcome is a change in fatigue as measured by the Piper Fatigue Scale (revised). Quality of life will be measured using the Quality of Life in Adult Survivors of Cancer Scale. Outcome measures will be collected at baseline, and at completion of intervention. Results The feasibility of trial procedures will be tested, as well as the effect of the intervention on the outcomes. Conclusions This study may lead to the development of a supportive resource to target representations and coping strategies of cancer survivors with CrF post-treatment. Setting Recruitment from general public in Ireland. Ethics and dissemination This trial was approved by the Research Ethics Committee at National University of Ireland Galway in January 2013. Trial results will be communicated in a peer-reviewed journal. Trial

  2. Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials.

    PubMed

    Ghislain, Irina; Zikos, Efstathios; Coens, Corneel; Quinten, Chantal; Balta, Vasiliki; Tryfonidis, Konstantinos; Piccart, Martine; Zardavas, Dimitrios; Nagele, Eva; Bjelic-Radisic, Vesna; Cardoso, Fatima; Sprangers, Mirjam A G; Velikova, Galina; Bottomley, Andrew

    2016-07-01

    Breast cancer is the leading cause of cancer death among women worldwide, and increasingly, randomised controlled trials of this disease are measuring the health-related quality of life of these patients. In this systematic Review, we assess the adequacy of methods used to report health-related quality of life (HRQOL) from 49 eligible randomised controlled trials of advanced breast cancer. We compare our findings with those from the literature to investigate whether the standard of HRQOL reporting in this field has changed. We conclude that the overall reporting of HRQOL has improved, but some crucial aspects remain problematic, such as the absence of HRQOL research hypotheses and the overemphasis on statistical rather than clinical significance. Additionally, new challenges are arising with the emergence of novel treatments and the advent of personalised medicine, and improved HRQOL tools are required to cover the range of side-effects of newer therapies.

  3. Prevention of oxaliplatin-induced peripheral neuropathy by a polyamine-reduced diet—NEUROXAPOL: protocol of a prospective, randomised, controlled, single-blind and monocentric trial

    PubMed Central

    Balayssac, David; Ferrier, Jérémy; Pereira, Bruno; Gillet, Brigitte; Pétorin, Caroline; Vein, Julie; Libert, Frédéric; Eschalier, Alain; Pezet, Denis

    2015-01-01

    Introduction Oxaliplatin remains the most widely used chemotherapeutic agent for treating advanced colorectal cancer but its efficacy is hampered by dose-limiting neurotoxicity manifested by a painful polyneuropathy. Oxaliplatin-induced peripheral neuropathy (OIPN) is characterised by acute and transient cold hyperaesthesia in the hours and days following oxaliplatin infusion (>90% of patients), but also by retarded chronic neuropathy due to the repetition of chemotherapy cycles (30–50% of patients). OIPN impairs the health-related quality of life (HRQOL) of patients and no preventive or curative strategies have as yet proven effective. A polyamine-reduced diet (PRD) has recently demonstrated its efficacy to prevent OIPN in animals without adverse effects. Methods and analysis The NEUROXAPOL trial is a prospective, randomised, controlled, single-blind, monocentric and interventional study. This trial is aimed at evaluating the efficacy and feasibility of a PRD compared to a normal polyamine containing diet to prevent OIPN in patients treated by oxaliplatin-based chemotherapy. Patients (n=40 per group) will be randomly assigned to receive either a PRD or a normal diet before and during the chemotherapy regimen. The main objectives are to improve the cold pain thresholds, neuropathic pain symptoms, comorbidities (anxiety and depression) and HRQOL of patients. The primary end point is the assessment of cold pain thresholds 2 weeks after the third cycle of chemotherapy. The secondary end points are the evaluation of thermal pain thresholds, the grade of neuropathy, neuropathic pain, symptoms of anxiety and depression and HRQOL, until the 12th cycle of chemotherapy. Ethics and dissemination The study was approved by an independent medical ethics committee 1 (CPP Sud Est 1, Saint Etienne, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international

  4. School‐based brief psycho‐educational intervention to raise adolescent cancer awareness and address barriers to medical help‐seeking about cancer: a cluster randomised controlled trial

    PubMed Central

    Stoddart, Iona; Forbat, Liz; Neal, Richard D.; O'Carroll, Ronan E.; Haw, Sally; Rauchhaus, Petra; Kyle, Richard G.

    2015-01-01

    Abstract Objectives Raising cancer awareness and addressing barriers to help‐seeking may improve early diagnosis. The aim was to assess whether a psycho‐educational intervention increased adolescents' cancer awareness and addressed help‐seeking barriers. Methods This was a cluster randomised controlled trial involving 2173 adolescents in 20 schools. The intervention was a 50‐min presentation delivered by a member of Teenage Cancer Trust's (UK charity) education team. Schools were stratified by deprivation and roll size and randomly allocated to intervention/control conditions within these strata. Outcome measures were the number of cancer warning signs and cancer risk factors recognised, help‐seeking barriers endorsed and cancer communication. Communication self‐efficacy and intervention fidelity were also assessed. Results Regression models showed significant differences in the number of cancer warning signs and risk factors recognised between intervention and control groups. In intervention schools, the greatest increases in recognition of cancer warning signs at 6‐month follow‐up were for unexplained weight loss (from 44.2% to 62.0%) and change in the appearance of a mole (from 46.3% to 70.7%), up by 17.8% and 24.4%, respectively. Greatest increases in recognition of cancer risk factors were for getting sunburnt more than once as a child (from 41.0% to 57.6%) and being overweight (from 42.7% to 55.5%), up by 16.6% and 12.8%, respectively. Regression models showed that adolescents in intervention schools were 2.7 times more likely to discuss cancer at 2‐week follow‐up compared with the control group. No differences in endorsement of barriers to help‐seeking were observed. Conclusions School‐based brief psycho‐educational interventions are easy to deliver, require little resource and improve cancer awareness. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd. PMID:26502987

  5. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain

    PubMed Central

    Allan, Laurie; Hays, Helen; Jensen, Niels-Henrik; de Waroux, Bernard Le Polain; Bolt, Michiel; Donald, Royden; Kalso, Eija

    2001-01-01

    Objectives To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. Design Randomised, multicentre, international, open label, crossover trial. Setting 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. Participants 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. Main outcome measures Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. Results Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being “good” or “very good” with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). Conclusion Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main

  6. Single-cell sequencing in cancer research.

    PubMed

    Mato Prado, Mireia; Frampton, Adam E; Stebbing, Justin; Krell, Jonathan

    2016-01-01

    Genome-wide single-cell sequencing investigations have the potential to classify individual cells within a tumor mass. In recent years, various single-cell DNA and RNA quantification techniques have facilitated significant advances in our ability to classify subpopulations of cells within a heterogeneous population. These approaches provide the possibility of unraveling the complex variability in genetic, epigenetic and transcriptional interactions that occur within identical cells in a tumor. This should enhance our knowledge of the underlying biological phenotypes and could have a huge impact in designing more precise anticancer treatments in order to improve outcomes and avoid tumor resistance. In addition, single-cell sequencing analysis has the potential to allow the development of better diagnostic and prognostic biomarkers, and thus aid the delivery of more personalized targeted cancer therapy. Nevertheless, further research is still required to overcome technical, biological and computational problems before clinical application.

  7. Aesthetic comparison between synthetic glue and subcuticular sutures in thyroid and parathyroid surgery: a single-blinded randomised clinical trial.

    PubMed

    Alicandri-Ciufelli, M; Piccinini, A; Grammatica, A; Molteni, G; Spaggiari, A; DI Matteo, S; Tassi, S; Ghidini, A; Izzo, L; Gioacchini, F M; Marchioni, D; DI Saverio, S; Presutti, L

    2014-12-01

    The aim of our study was to compare, in terms of aesthetic results, the use of synthetic glue to intradermal absorbable sutures in postthyroidectomy and parathyroidectomy wound closure in a single blinded, randomised, per protocol equivalence study. From September 2008 to May 2010, patients undergoing thyroid or parathyroid surgery (with an external approach) at the Otolaryngology Department of the University Hospital of Modena were assessed for eligibility. In total, 42 patients who had had synthetic glue application on surgical incisions (A) and 47 patients who had subcuticular sutures on their surgical incisions (B) were enrolled. The mean of the endpoint (based on the Wound Registry Scale) of group A at 10 days was 1.4, while that in group B (based on the Stony Brook Scar Evaluation Scale) was 2.9. Statistically significant (p = 0.002) and clinically significant (difference of the means = 1.5) differences in the aesthetic results were found between groups A and B at 10 days, with better results in group B. On the other hand, at 3 months, the mean of the endpoint in group A was 3.1 while that in group B was 2.8; no statistically significant (p = 0.62) or clinically significant (difference in means = 0.3) differences were found between groups A and B. In conclusion, synthetic glue differs from subcuticular suture in post-thyroidectomy or post-parathyroidectomy incision for early aesthetic results, with better outcomes for subcuticular sutures. At 3 months, there were no differences in aesthetic outcomes between groups. Moreover, sex, incision length, age, cold/hot blade and correspondence of the incision with a wrinkle in the skin did not seem to influence aesthetic outcomes with this type of incision.

  8. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial

    PubMed Central

    FOxTROT Collaborative Group

    2012-01-01

    Summary Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more effective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more effective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and efficacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m2, l-folinic acid 175 mg, fluorouracil 400 mg/m2 bolus, then 2400 mg/m2 by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the first 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratification variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no significant differences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had

  9. Decrease social inequalities return-to-work: development and design of a randomised controlled trial among women with breast cancer

    PubMed Central

    2014-01-01

    Background Despite the improvement in the care management, women cancer patients who are still in employment find themselves for the most part obliged to stop working while they are having treatment. Their return-to-work probability is impacted by numerous psychosocial factors. The objective is to describe the development and the content of an intervention aimed to facilitate the return to work of female breast cancer patients and in particular the women in the most precarious situations through early active individualised psychosocial support (APAPI). Methods The intervention proposed is made up of 4 interviews with a psychologist at the hospital, distributed over the year according to the diagnosis and conducted on the same day as a conventional follow-up consultation, then a consultation with a specialist job retention physician. We expect, in the first instance, that this intervention will reduce the social inequalities of the return-to-work rate at 12 months. The EPICES score will enable the population to be broken down according to the level of social precariousness. The other expected results are the reduction of the social inequalities in the quality of the return to work at 18 and 24 months and the disparities between the individual and collective resources of the patients. This intervention is assessed in the context of a controlled and randomised multi-centre study. The patients eligible are women aged between 18 and 55 years with a unilateral breast cancer with local extension exclusively, having received surgery followed by adjuvant chemotherapy, in employment at the time of the diagnosis and dealt with by one of the 2 investigating centres. Discussion It is essential to assess this type of intervention before envisaging its generalisation. The study set in place will enable us to measure the impact of this intervention aiming to facilitate the return to work of breast cancer patients, in particular for those who suffer from social fragility

  10. General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled trial

    PubMed Central

    Wattchow, D A; Weller, D P; Esterman, A; Pilotto, L S; McGorm, K; Hammett, Z; Platell, C; Silagy, C

    2006-01-01

    This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4–4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5–1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3–1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes, although patterns of investigation vary. PMID:16622437

  11. A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers.

    PubMed

    Ciuleanu, T; Diculescu, M; Hoepffner, N M; Trojan, J; Sailer, V; Zalupski, M; Herrmann, T; Roth, A; Chick, J; Brock, K; Albert, D; Philip, P A

    2007-08-01

    The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5-FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated.

  12. Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

    PubMed Central

    Vollset, Stein Emil; Clarke, Robert; Lewington, Sarah; Ebbing, Marta; Halsey, Jim; Lonn, Eva; Armitage, Jane; Manson, JoAnn E; Hankey, Graeme J; Spence, J David; Galan, Pilar; Bønaa, Kaare H; Jamison, Rex; Gaziano, J Michael; Guarino, Peter; Baron, John A; Logan, Richard FA; Giovannucci, Edward L; den Heijer, Martin; Ueland, Per M; Bennett, Derrick; Collins, Rory; Peto, Richard

    2013-01-01

    Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials. Methods Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period. Findings During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency. PMID:23352552

  13. Dietary supplements and prostate cancer: a systematic review of double-blind, placebo-controlled randomised clinical trials.

    PubMed

    Posadzki, Paul; Lee, Myeong Soo; Onakpoya, Igho; Lee, Hye Won; Ko, Byong Seob; Ernst, Edzard

    2013-06-01

    Dietary supplements are popular among patients with prostate cancer (PC). The objective of this systematic review was to critically examine double-blind, placebo-controlled randomised clinical trials (RCTs) of non-herbal dietary supplements and vitamins (NHDS) for evidence that prostate specific antigen (PSA) levels were reduced in PC patients. Five databases were searched from their inception through December 2012 to identify studies that met our inclusion criteria. Methodological quality was independently assessed by two reviewers using the Cochrane tool. Eight RCTs met the eligibility criteria and were of high methodological quality. The following supplements were tested: isoflavones (genistein, daidzein, and glycitein), minerals (Se) or vitamins (vitamin D) or a combination of antioxidants, bioflavonoids, carotenoids, lycopenes, minerals (Se, Zn, Cu, and Mg), phytoestrogens, phytosterols, vitamins (B2, B6, B9, B12, C, and E), and other substances (CoQ10 and n-acetyl-l cysteine). Five RCTs reported no significant effects compared with placebo. Two RCTs reported that a combination of antioxidants, isoflavones, lycopenes, minerals, plant oestrogens and vitamins significantly decreased PSA levels compared with placebo. One RCT did not report differences in PSA levels between the groups. In conclusion, the hypothesis that dietary supplements are effective treatments for PC patients is not supported by sound clinical evidence. There are promising data for only two specific remedies, which contained a mixture of ingredients, but even for these supplements, additional high quality evidence is necessary before firm recommendations would be justified.

  14. Factors associated with non-participation and dropout among cancer patients in a cluster-randomised controlled trial.

    PubMed

    Roick, J; Danker, H; Kersting, A; Briest, S; Dietrich, A; Dietz, A; Einenkel, J; Papsdorf, K; Lordick, F; Meixensberger, J; Mössner, J; Niederwieser, D; Prietzel, T; Schiefke, F; Stolzenburg, J-U; Wirtz, H; Singer, S

    2017-01-30

    We investigated the impact of demographic and disease related factors on non-participation and dropout in a cluster-randomised behavioural trial in cancer patients with measurements taken between hospitalisation and 6 months thereafter. The percentages of non-participation and dropout were documented at each time point. Factors considered to be potentially related with non-participation and dropout were as follows: age, sex, marital status, education, income, employment status, tumour site and stage of disease. Of 1,338 eligible patients, 24% declined participation at baseline. Non-participation was higher in older patients (Odds Ratio [OR] 2.1, CI: 0.6-0.9) and those with advanced disease (OR 2.0, CI: 0.1-1.3). Dropout by 6 months was 25%. Dropout was more frequent with increased age (OR 2.8, CI: 0.8-1.2), advanced disease (OR 3.0, CI: 1.0-1.2), being married (OR 2.4, CI 0.7-1.1) and less frequent with university education (OR 0.4, CI -1.3 to -0.8) and middle income (OR 0.4, CI -0.9 to -0.7). When planning clinical trials, it is important to be aware of patient groups at high risk of non-participation or dropout, for example older patients or those with advanced disease. Trial designs should consider their special needs to increase their rate of participation.

  15. Study protocol for a randomised controlled trial of brief, habit-based, lifestyle advice for cancer survivors: exploring behavioural outcomes for the Advancing Survivorship Cancer Outcomes Trial (ASCOT)

    PubMed Central

    Beeken, Rebecca J; Croker, Helen; Heinrich, Maggie; Smith, Lee; Williams, Kate; Hackshaw, Allan; Hines, John; Machesney, Michael; Krishnaswamy, Madhavan; Cavanagh, Sharon; Roylance, Rebecca; Hill, Alison; Pritchard-Jones, Kathy; Wardle, Jane; Fisher, Abigail

    2016-01-01

    Introduction Positive health behaviours such as regular physical activity and a healthy diet have significant effects on cancer outcomes. There is a need for simple but effective behaviour change interventions with the potential to be implemented within the cancer care pathway. Habit-based advice encourages repetition of a behaviour in a consistent context so that the behaviour becomes increasingly automatic in response to a specific contextual cue. This approach therefore encourages long-term behaviour change and can be delivered through printed materials. ‘Healthy Habits for Life’ is a brief intervention based on habit theory, and incorporating printed materials plus a personally tailored discussion, that has been designed specifically for patients with a diagnosis of cancer. The aim of this trial was to test the effect of ‘Healthy Habits for Life’ on a composite health behaviour risk index (CHBRI) over 3 months in patients with a diagnosis of breast, colorectal or prostate cancer. Method and analysis A 2-arm, individually randomised controlled trial in patients with breast, colorectal and prostate cancer. Patients will be recruited over 18 months from 7 National Health Service Trusts in London and Essex. Following baseline assessments and allocation to intervention or usual care, patients are followed up at 3 and 6 months. The primary outcome will be change in CHBRI at 3 months. Maintenance of any changes over 6 months, and changes in individual health behaviours (including dietary intake, physical activity, alcohol consumption and smoking status) will also be explored. Ethics and dissemination Ethical approval was obtained through the National Research Ethics Service Committee South Central—Oxford B via the Integrated Research Application System (reference number 14/SC/1369). Results of this study will be disseminated through peer-reviewed publications and scientific presentations. Trial registration number 17421871. PMID:27881518

  16. EVerT2—needling versus non-surgical debridement for the treatment of verrucae: study protocol for a single-centre randomised controlled trial

    PubMed Central

    Hashmi, Farina; Torgerson, David; Fairhurst, Caroline; Cockayne, Sarah; Bell, Kerry; Cullen, Michelle; Harrison-Blount, Michael

    2015-01-01

    Introduction Verrucae are extremely common, and are experienced by most people at some time during their lives. Although most verrucae will spontaneously disappear without treatment, many patients seek treatment, often because they have persisted for many years, are unsightly or painful or prevent them from doing sports or other activities. There are many different treatments available; including the Falknor's needling procedure. To date, there has only been one small trial evaluating the clinical effectiveness of this treatment and no health economic analysis has been undertaken. The Effective Verruca Treatments (EVerT2) trial aims to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of verrucae. Methods and analysis This single-centre randomised controlled trial will recruit 58 participants (aged 18 years and over with a plantar verruca) from Salford Podiatry Clinic patient lists and the surrounding area. If the participant presents with multiple verrucae, an ‘index’ verruca (largest and thickest lesion) will be identified and patients will be randomised 1:1 to the intervention group to receive the needling treatment or the control group to have the callus overlying the verruca debrided. The primary outcome is complete clearance of the index verruca at 12 weeks after randomisation. Secondary outcomes include clearance and recurrence of the treated verruca, clearance of all verrucae, number of verrucae remaining, change in size of the index verruca, pain, and participant satisfaction. A cost-effectiveness analysis of the needling versus callus debridement will be carried out from the perspective of health services over a time horizon of 12 weeks. Ethics and dissemination Ethical approval has been obtained from the University of Salford, Department of Health Sciences Ethical Approval Committee (HSCR15/24) and the University of York, Department of Health Sciences Research Governance Committee (HSRGC/2014/98/B

  17. Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement. A randomised, controlled trial.

    PubMed

    Verhamme, Peter; Gunn, Sophie; Sonesson, Elisabeth; Peerlinck, Kathelijne; Vanassche, Thomas; Vandenbriele, Christophe; Ageno, Walter; Glazer, Steven; Prins, Martin; Buller, Harry; Tangelder, Marco

    2013-06-01

    TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2-4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9-9.6), 5.2% (95%CI 2.8-9.3) and 4.7% (95%CI 2.5-8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3-9.9), 7.2% (95%CI 4.4-11.6) and 1.4% (95%CI 0.5-4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.

  18. Visual cue training to improve walking and turning after stroke: a study protocol for a multi-centre, single blind randomised pilot trial

    PubMed Central

    2013-01-01

    Background Visual information comprises one of the most salient sources of information used to control walking and the dependence on vision to maintain dynamic stability increases following a stroke. We hypothesize, therefore, that rehabilitation efforts incorporating visual cues may be effective in triggering recovery and adaptability of gait following stroke. This feasibility trial aims to estimate probable recruitment rate, effect size, treatment adherence and response to gait training with visual cues in contrast to conventional overground walking practice following stroke. Methods/design A 3-arm, parallel group, multi-centre, single blind, randomised control feasibility trial will compare overground visual cue training (O-VCT), treadmill visual cue training (T-VCT), and usual care (UC). Participants (n = 60) will be randomly assigned to one of three treatments by a central randomisation centre using computer generated tables to allocate treatment groups. The research assessor will remain blind to allocation. Treatment, delivered by physiotherapists, will be twice weekly for 8 weeks at participating outpatient hospital sites for the O-VCT or UC and in a University setting for T-VCT participants. Individuals with gait impairment due to stroke, with restricted community ambulation (gait speed <0.8m/s), residual lower limb paresis and who are able to take part in repetitive walking practice involving visual cues (i.e., no severe visual impairments, able to walk with minimal assistance and no comorbid medical contraindications for walking practice) will be included. The primary outcomes concerning participant enrolment, recruitment, retention, and health and social care resource use data will be recorded over a recruitment period of 18 months. Secondary outcome measures will be undertaken before randomisation (baseline), after the eight-week intervention (outcome), and at three months (follow-up). Outcome measures will include gait speed and step length symmetry

  19. Non-contact low-frequency ultrasound therapy compared with UK standard of care for venous leg ulcers: a single-centre, assessor-blinded, randomised controlled trial.

    PubMed

    White, Judith; Ivins, Nicola; Wilkes, Antony; Carolan-Rees, Grace; Harding, Keith G

    2016-10-01

    'Hard-to-heal' wounds are those which fail to heal with standard therapy in an orderly and timely manner and may warrant the use of advanced treatments such as non-contact low-frequency ultrasound (NLFU) therapy. This evaluator-blinded, single-site, randomised controlled trial, compared NLFU in addition to UK standard of care [SOC: (NLFU + SOC)] three times a week, with SOC alone at least once a week. Patients with chronic venous leg ulcers were eligible to participate. All 36 randomised patients completed treatment (17 NLFU + SOC, 19 SOC), and baseline demographics were comparable between groups. NLFU + SOC patients showed a -47% (SD: 38%) change in wound area; SOC, -39% (38%) change; and difference, -7·4% [95% confidence intervals (CIs) -33·4-18·6; P = 0·565]. The median number of infections per patient was two in both arms of the study and change in quality of life (QoL) scores was not significant (P = 0·490). NLFU + SOC patients reported a substantial mean (SD) reduction in pain score of -14·4 (14·9) points, SOC patients' pain scores reduced by -5·3 (14·8); the difference was -9·1 (P = 0·078). Results demonstrated the importance of high-quality wound care. Outcome measures favoured NLFU + SOC over SOC, but the differences were not statistically significant. A larger sample size and longer follow-up may reveal NLFU-related improvements not identified in this study.

  20. Online group-based cognitive-behavioural therapy for adolescents and young adults after cancer treatment: A multicenter randomised controlled trial of Recapture Life-AYA

    PubMed Central

    2012-01-01

    Background A cancer diagnosis is 2.9 times more likely to occur during the adolescent and young adult years than in younger children. This spike in incidence coincides with a life stage characterised by psychological vulnerability as young people strive to attain numerous, critical developmental milestones. The distress young people experience after cancer treatment seriously jeopardises their ability to move into well-functioning adulthood. Methods/Design This article presents the protocol of the Recapture Life study, a phase II three-arm randomised controlled trial designed to evaluate the feasibility and efficacy of a new intervention in reducing distress and improving quality of life for adolescent and young adult cancer survivors. The novel intervention, “ReCaPTure LiFe” will be compared to a both a wait-list, and a peer-support group control. Ninety young people aged 15–25 years who have completed cancer treatment in the past 1–6 months will be recruited from hospitals around Australia. Those randomised to receive Recapture Life will participate in six, weekly, 90-minute online group sessions led by a psychologist, involving peer-discussion around cognitive-behavioural coping skills (including: behavioural activation, thought challenging, communication and assertiveness skills training, problem-solving and goal-setting). Participants randomised to the peer-support group control will receive non-directive peer support delivered in an identical manner. Participants will complete psychosocial measures at baseline, post-intervention, and 12-months post-intervention. The primary outcome will be quality of life. Secondary outcomes will include depression, anxiety, stress, family functioning, coping, and cancer-related identity. Discussion This article reviews the empirical rationale for using group-based, online cognitive-behavioural therapy in young people after cancer treatment. The potential challenges of delivering skills-based programs in an online

  1. CanWalk: a feasibility study with embedded randomised controlled trial pilot of a walking intervention for people with recurrent or metastatic cancer

    PubMed Central

    Tsianakas, Vicki; Ream, Emma; Van Hemelrijck, Mieke; Purushotham, Arnie; Mucci, Lorelei; Green, James S A; Fewster, Jacquetta; Armes, Jo

    2017-01-01

    Objectives Walking is an adaptable, inexpensive and accessible form of physical activity. However, its impact on quality of life (QoL) and symptom severity in people with advanced cancer is unknown. This study aimed to assess the feasibility and acceptability of a randomised controlled trial (RCT) of a community-based walking intervention to enhance QoL in people with recurrent/metastatic cancer. Design We used a mixed-methods design comprising a 2-centre RCT and nested qualitative interviews. Participants Patients with advanced breast, prostate, gynaecological or haematological cancers randomised 1:1 between intervention and usual care. Intervention The intervention comprised Macmillan's ‘Move More’ information, a short motivational interview with a recommendation to walk for at least 30 min on alternate days and attend a volunteer-led group walk weekly. Outcomes We assessed feasibility and acceptability of the intervention and RCT by evaluating study processes (rates of recruitment, consent, retention, adherence and adverse events), and using end-of-study questionnaires and qualitative interviews. Patient-reported outcome measures (PROMs) assessing QoL, activity, fatigue, mood and self-efficacy were completed at baseline and 6, 12 and 24 weeks. Results We recruited 42 (38%) eligible participants. Recruitment was lower than anticipated (goal n=60), the most commonly reported reason being unable to commit to walking groups (n=19). Randomisation procedures worked well with groups evenly matched for age, sex and activity. By week 24, there was a 45% attrition rate. Most PROMs while acceptable were not sensitive to change and did not capture key benefits. Conclusions The intervention was acceptable, well tolerated and the study design was judged acceptable and feasible. Results are encouraging and demonstrate that exercise was popular and conveyed benefit to participants. Consequently, an effectiveness RCT is warranted, with some modifications to the

  2. Community-randomised controlled trial embedded in the Anishinaabek Cervical Cancer Screening Study: human papillomavirus self-sampling versus Papanicolaou cytology

    PubMed Central

    Zehbe, Ingeborg; Jackson, Robert; Wood, Brianne; Weaver, Bruce; Escott, Nicholas; Severini, Alberto; Krajden, Mel; Bishop, Lisa; Morrisseau, Kyla; Ogilvie, Gina; Burchell, Ann N; Little, Julian

    2016-01-01

    Objectives The incidence of cervical cancer is up to 20-fold higher among First Nations women in Canada than the general population, probably due to lower participation in screening. Offering human papillomavirus (HPV) self-sampling in place of Papanicolaou (Pap) testing may eventually increase screening participation and reduce cervical cancer rates in this population. Design A community-randomised controlled screening trial. Setting First Nations communities in Northwest Ontario, Canada. Participants Women aged between 25 and 69, living in Robinson Superior Treaty First Nations. The community was the unit of randomisation. Interventions Women were asked to complete a questionnaire and have screening by HPV self-sampling (arm A) or Pap testing (arm B). Primary outcome measures The number of women who participated in cervical screening. Randomisation Community clusters were randomised to include approximately equivalent numbers of women in each arm. Results 6 communities were randomised to arm A and 5 to arm B. One community withdrew, leaving 5 communities in each group (834 eligible women). Participation was <25%. Using clustered intention-to-treat (ITT) analysis, initial and cumulative averaged uptakes in arm A were 1.4-fold (20% vs 14.3%, p=0.628) and 1.3-fold (20.6% vs 16%, p=0.694) higher compared to arm B, respectively. Corresponding per protocol (PP) analysis indicates 2.2-fold (22.9% vs 10.6%, p=0.305) and 1.6-fold (22.9% vs 14.1%, p=0.448) higher uptakes in arm A compared to arm B. Screening uptake varied between communities (range 0–62.1%). Among women who completed a questionnaire (18.3% in arm A, 21.7% in arm B), the screening uptake was 1.8-fold (ITT; p=0.1132) or 3-fold (PP; p<0.01) higher in arm A versus arm B. Conclusions Pap and HPV self-sampling were compared in a marginalised, Canadian population. Results indicated a preference for self-sampling. More research on how to reach underscreened Indigenous women is necessary. Trial registration

  3. Positive psychology group intervention for breast cancer patients: a randomised trial.

    PubMed

    Victoria Cerezo, M; Ortiz-Tallo, Margarita; Cardenal, Violeta; De La Torre-Luque, Alejandro

    2014-08-01

    This study assessed the effects of a psychological group intervention based on positive psychology in women with breast cancer. 175 women were randomly assigned either to an experimental group, receiving the 14-session intervention (n = 87), or to a wait list group (n = 88) that did not receive any type of intervention. For treatment, a group intervention was applied, based on improving psychological strengths and enhancing positive psychology-based styles of coping. Strength-related outcomes, self-esteem, well-being, and happiness were assessed before and after the intervention. The experimental group showed higher scores on all of the study variables after the intervention. Participants reported improved self-esteem, emotional intelligence-related abilities, resilience, and optimism, as well as positive affectivity, well-being, and happiness. The results show a beneficial effect of this psychological intervention based on positive psychology on female breast cancer patients' psychological health.

  4. Exploring the feasibility and acceptability of couple-based psychosexual support following prostate cancer surgery: study protocol for a pilot randomised controlled trial

    PubMed Central

    2014-01-01

    Background Men who undergo surgery for prostate cancer frequently experience significant side-effects including urinary and sexual dysfunction. These difficulties can lead to anxiety, depression and reduced quality of life. Many partners also experience psychological distress. An additional impact can be on the couple relationship, with changes to intimacy, and unmet psychosexual supportive needs in relation to sexual recovery and rehabilitation. The aim of this exploratory randomised controlled trial pilot study is to determine the feasibility and acceptability of a novel family-relational-psychosexual intervention to support intimacy and reduce distress among couples following prostate cancer surgery and to estimate the efficacy of this intervention. Methods/Design The intervention will comprise six sessions of psychosexual and relationship support delivered by experienced couple-support practitioners. Specialist training in delivering the intervention will be provided to practitioners and they will be guided by a detailed treatment manual based on systemic principles. Sixty-eight couples will be randomised to receive either the intervention or standard care (comprising usual follow-up hospital appointments). A pre-test, post-test design will be used to test the feasibility of the intervention (baseline, end of intervention and six-month follow-up) and its acceptability to couples and healthcare professionals (qualitative interviews). Both individual and relational outcome measures will assess sexual functioning, anxiety and depression, couple relationship, use of health services and erectile dysfunction medication/technologies. An economic analysis will estimate population costs of the intervention, compared to usual care, using simple modelling to evaluate the affordability of the intervention. Discussion Given the increasing incidence and survival of post-operative men with prostate cancer, it is timely and appropriate to determine the feasibility of a

  5. A randomised comparison of the single use LMA Flexible with the reusable LMA Flexible in paediatric dental day-case patients.

    PubMed

    Flynn, P; Ahmed, F B; Mitchell, V; Patel, A; Clarke, S

    2007-12-01

    In this study we compared the performance of the single use flexible laryngeal mask airway (LMA Flexible) with the original reusable LMA Flexible in paediatric dento-alveolar day-case surgery. The aim of the study was to determine whether these two supraglottic airway devices were clinically equivalent when used for simple dental extractions in children under general anaesthesia. This randomised comparative trial in 100 healthy children used first attempt airway insertion success as its primary outcome measure. Secondary outcomes included the adequacy of ventilation, incidence of airway obstruction and the requirement for device manipulation and the incidence of adverse airway outcomes during recovery from anaesthesia. No difference was found between the devices in first attempt insertion success rate (94% with reusable LMA Flexible and 90% with single use LMA Flexible, p = 0.358), and ease of insertion was also similar (p = 0.5). Both devices performed equally well during surgery, with no significant differences in episodes of intra-operative airway compromise (p = 0.387), and both the single use and reusable LMA Flexible displayed excellent recovery characteristics, with no occurrences of emergence airway obstruction. No blood was discovered within the inner LMA tube shaft in either device, implying that both protected against tracheobronchial soiling. We conclude therefore that the single use LMA Flexible is an acceptable alternative to the reusable LMA Flexible.

  6. Cost-effectiveness analysis of an 18-week exercise programme for patients with breast and colon cancer undergoing adjuvant chemotherapy: the randomised PACT study

    PubMed Central

    May, Anne M; Bosch, Marcel J C; Velthuis, Miranda J; van der Wall, Elsken; Steins Bisschop, Charlotte N; Los, Maartje; Erdkamp, Frans; Bloemendal, Haiko J; de Roos, Marnix A J; Verhaar, Marlies; ten Bokkel Huinink, Daan; Peeters, Petra H M; de Wit, G Ardine

    2017-01-01

    Objective Meta-analyses show that exercise interventions during cancer treatment reduce cancer-related fatigue. However, little is known about the cost-effectiveness of such interventions. Here we aim to assess the cost-effectiveness of the 18-week physical activity during cancer treatment (PACT) intervention for patients with breast and colon cancer. The PACT trial showed beneficial effects for fatigue and physical fitness. Design Cost-effectiveness analyses with a 9-month time horizon (18 weeks of intervention and 18 weeks of follow-up) within the randomised controlled multicentre PACT study. Setting Outpatient clinics of 7 hospitals in the Netherlands (1 academic and 6 general hospitals) Participants 204 patients with breast cancer and 33 with colon cancer undergoing adjuvant treatment including chemotherapy. Intervention Supervised 1-hour aerobic and resistance exercise (twice per week for 18 weeks) or usual care. Main outcome measures Costs, quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio. Results For colon cancer, the cost-effectiveness analysis showed beneficial effects of the exercise intervention with incremental costs savings of €4321 and QALY improvements of 0.03. 100% of bootstrap simulations indicated that the intervention is dominant (ie, cheaper and more effective). For breast cancer, the results did not indicate that the exercise intervention was cost-effective. Incremental costs were €2912, and the incremental effect was 0.01 QALY. At a Dutch threshold value of €20 000 per QALY, the probability that the intervention is cost-effective was 2%. Conclusions Our results suggest that the 18-week exercise programme was cost-effective for colon cancer, but not for breast cancer. Trial registration number ISRCTN43801571. PMID:28264824

  7. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study

    PubMed Central

    Österlund, P; Ruotsalainen, T; Korpela, R; Saxelin, M; Ollus, A; Valta, P; Kouri, M; Elomaa, I; Joensuu, H

    2007-01-01

    5-Fluorouracil (5-FU)-based chemotherapy is frequently associated with diarrhoea. We compared two 5-FU-based regimens and the effect of Lactobacillus and fibre supplementation on treatment tolerability. Patients diagnosed with colorectal cancer (n=150) were randomly allocated to receive monthly 5-FU and leucovorin bolus injections (the Mayo regimen) or a bimonthly 5-FU bolus plus continuous infusion (the simplified de Gramont regimen) for 24 weeks as postoperative adjuvant therapy. On the basis of random allocation, the study participants did or did not receive Lactobacillus rhamnosus GG supplementation (1–2 × 1010 per day) and fibre (11 g guar gum per day) during chemotherapy. Patients who received Lactobacillus had less grade 3 or 4 diarrhoea (22 vs 37%, P=0.027), reported less abdominal discomfort, needed less hospital care and had fewer chemotherapy dose reductions due to bowel toxicity. No Lactobacillus-related toxicity was detected. Guar gum supplementation had no influence on chemotherapy tolerability. The simplified de Gramont regimen was associated with fewer grade 3 or 4 adverse effects than the Mayo regimen (45 vs 89%), and with less diarrhoea. We conclude that Lactobacillus GG supplementation is well tolerated and may reduce the frequency of severe diarrhoea and abdominal discomfort related to 5-FU-based chemotherapy. PMID:17895895

  8. Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study

    PubMed Central

    Touillaud, M; Foucaut, A-M; Berthouze, S E; Reynes, E; Kempf-Lépine, A-S; Carretier, J; Pérol, D; Guillemaut, S; Chabaud, S; Bourne-Branchu, V; Perrier, L; Trédan, O; Fervers, B; Bachmann, P

    2013-01-01

    Introduction After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients’ satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. Methods and analysis The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. Ethics and dissemination The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy

  9. Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

    PubMed Central

    2013-01-01

    Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

  10. A randomised controlled trial to assess the effectiveness of a single session of nurse administered massage for short term relief of chronic non-malignant pain

    PubMed Central

    Seers, Kate; Crichton, Nicola; Martin, June; Coulson, Katrina; Carroll, Dawn

    2008-01-01

    Background Massage is increasingly used to manage chronic pain but its benefit has not been clearly established. The aim of the study is to determine the effectiveness of a single session of nurse-administered massage for the short term relief of chronic non-malignant pain and anxiety. Methods A randomised controlled trial design was used, in which the patients were assigned to a massage or control group. The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain. Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study. An observer blind to the patients' treatment group carried out assessments immediately before (baseline), after treatment and 1, 2, 3 and 4 hours later. Pain was assessed using 100 mm visual analogue scale and the McGill Pain Questionnaire. Pain Relief was assessed using a five point verbal rating scale. Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory. Results 101 patients were randomised and evaluated, 50 in the massage and 51 in the control group. There were no statistically significant differences between the groups at baseline interview. Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment. 95% confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47 mm to 24.70 mm. Patients in the massage but not the control group had a statistically significant reduction in anxiety compared to baseline immediately after and at 1 hour post treatment. Conclusion Massage is effective in the short term for chronic pain of moderate to severe intensity. Trial Registration [ISRCTN98406653] PMID:18601729

  11. Asperger syndrome and anxiety disorders (PAsSA) treatment trial: a study protocol of a pilot, multicentre, single-blind, randomised crossover trial of group cognitive behavioural therapy

    PubMed Central

    Langdon, Peter E; Murphy, Glynis H; Wilson, Edward; Shepstone, Lee; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra

    2013-01-01

    Introduction A number of studies have established that children, adolescents and adults with Asperger syndrome (AS) and high functioning autism (HFA) have significant problems with anxiety. Cognitive behavioural therapy (CBT) is an effective treatment for anxiety in a variety of clinical populations. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems, but currently there are no known clinical trials involving adults with AS or HFA. Studies with children who have AS have reported some success. The current study aims to examine whether modified group CBT for clinically significant anxiety in an AS population is likely to be efficacious. Methods and analysis This study is a randomised, single-blind crossover trial. At least 36 individuals will be recruited and randomised into a treatment arm or a waiting-list control arm. During treatment, individuals will receive 3 sessions of individual CBT, followed by 21 sessions of group CBT. Primary outcome measures focus on anxiety. Secondary outcome measures focus on everyday social and psychiatric functioning, additional measures of anxiety and fear, depression, health-related quality of life and treatment cost. Assessments will be administered at pregroup and postgroup and at follow-up by researchers who are blinded to group allocation. The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS. Furthermore, we aim to determine whether this intervention represents good value for money. Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service (NHS) Research Ethics Committee. All participants provided written informed consent. Findings will be shared with all trial participants, and the general public, as well as the scientific community. Trial Registration ISRCTN 30265294 (DOI: 10.1186/ISRCTN30265294), UKCRN

  12. Increasing Cervical Cancer Screening Coverage: A Randomised, Community-Based Clinical Trial

    PubMed Central

    Acera, Amelia; Manresa, Josep Maria; Rodriguez, Diego; Rodriguez, Ana; Bonet, Josep Maria; Trapero-Bertran, Marta; Hidalgo, Pablo; Sànchez, Norman

    2017-01-01

    Background Opportunistic cervical cancer screening can lead to suboptimal screening coverage. Coverage could be increased after a personalised invitation to the target population. We present a community randomized intervention study with three strategies aiming to increase screening coverage. Methods The CRICERVA study is a community-based clinical trial to improve coverage of population-based screening in the Cerdanyola SAP area in Barcelona.A total of 32,858 women residing in the study area, aged 30 to 70 years were evaluated. A total of 15,965 women were identified as having no registration of a cervical cytology in the last 3.5 years within the Public Health data base system. Eligible women were assigned to one of four community randomized intervention groups (IGs): (1) (IG1 N = 4197) personalised invitation letter, (2) (IG2 N = 3601) personalised invitation letter + informative leaflet, (3) (IG3 N = 6088) personalised invitation letter + informative leaflet + personalised phone call and (4) (Control N = 2079) based on spontaneous demand of cervical cancer screening as officially recommended. To evaluate screening coverage, we used heterogeneity tests to compare impact of the interventions and mixed logistic regression models to assess the age effect. We refer a “rescue” visit as the screening visit resulting from the study invitation. Results Among the 13,886 women in the IGs, 2,862 were evaluated as having an adequate screening history after the initial contact; 4,263 were lost to follow-up and 5,341 were identified as having insufficient screening and thus being eligible for a rescue visit. All intervention strategies significantly increased participation to screening compared to the control group. Coverage after the intervention reached 84.1% while the control group reached 64.8%. The final impact of our study was an increase of 20% in the three IGs and of 9% in the control group (p<0.001). Within the intervention arms, age was an important determinant

  13. Efficacy of 'radioguided occult lesion localisation' (ROLL) versus 'wire-guided localisation' (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial.

    PubMed

    Postma, E L; Verkooijen, H M; van Esser, S; Hobbelink, M G; van der Schelling, G P; Koelemij, R; Witkamp, A J; Contant, C; van Diest, P J; Willems, S M; Borel Rinkes, I H M; van den Bosch, M A A J; Mali, W P; van Hillegersberg, R

    2012-11-01

    For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisation. Women (>18 years.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99 m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with negative margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86 %) patients in the ROLL group versus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) patients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). No significant differences were seen in the duration and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first

  14. Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial

    PubMed Central

    Navani, Neal; Nankivell, Matthew; Lawrence, David R; Lock, Sara; Makker, Himender; Baldwin, David R; Stephens, Richard J; Parmar, Mahesh K; Spiro, Stephen G; Morris, Stephen; Janes, Sam M

    2015-01-01

    Summary Background The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer. Methods In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769. Findings Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14–15) than with CDS (29 days; 23–35) resulting in a hazard ratio of 1·98, (1·39–2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage

  15. Improving swallowing outcomes in patients with head and neck cancer using a theory-based pretreatment swallowing intervention package: protocol for a randomised feasibility study

    PubMed Central

    Smith, Christina H; Barratt, Helen; Taylor, Stuart A

    2017-01-01

    Introduction The incidence of head and neck cancer (HNC) in the UK is rising, with an average of 31 people diagnosed daily. Patients affected by HNC suffer significant short-term and long-term post-treatment morbidity as a result of dysphagia, which affects daily functioning and quality of life (QOL). Pretreatment swallowing exercises may provide additional benefit over standard rehabilitation in managing dysphagia after primary HNC treatments, but uncertainty about their effectiveness persists. This study was preceded by an intervention development phase to produce an optimised swallowing intervention package (SIP). The aim of the current study is to assess the feasibility of this new intervention and research processes within a National Health Service (NHS) setting. Method and analysis A two-arm non-blinded randomised controlled feasibility study will be carried out at one tertiary referral NHS centre providing specialist services in HNC. Patients newly diagnosed with stage III and IV disease undergoing planned surgery and/or chemoradiation treatments will be eligible. The SIP will be delivered pre treatment, and a range of swallowing-related and QOL measures will be collected at baseline, 1, 3 and 6 months post-treatment. Outcomes will test the feasibility of a future randomised controlled trial (RCT), detailing rate of recruitment and patient acceptance to participation and randomisation. Salient information relating to protocol implementation will be collated and study material such as the case report form will be tested. A range of candidate outcome measures will be examined for suitability in a larger RCT. Ethics and dissemination Ethical approval was obtained from an NHS Research Ethics Committee. Findings will be published open access in a peer-reviewed journal, and presented at relevant conferences and research meetings. Trial registration number ISRCTN40215425; Pre-results. PMID:28348190

  16. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

    PubMed Central

    Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

    2016-01-01

    Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

  17. A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol.

    PubMed

    Pascoe, Steven J; Lipson, David A; Locantore, Nicholas; Barnacle, Helen; Brealey, Noushin; Mohindra, Rajat; Dransfield, Mark T; Pavord, Ian; Barnes, Neil

    2016-08-01

    Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017.

  18. Cost-effectiveness and quality of life in surgeon versus general practitioner-organised colon cancer surveillance: a randomised controlled trial

    PubMed Central

    Augestad, Knut Magne; Norum, Jan; Dehof, Stefan; Aspevik, Ranveig; Ringberg, Unni; Nestvold, Torunn; Vonen, Barthold; Skrøvseth, Stein Olav; Lindsetmo, Rolv-Ole

    2013-01-01

    Objective To assess whether colon cancer follow-up can be organised by general practitioners (GPs) without a decline in the patient's quality of life (QoL) and increase in cost or time to cancer diagnoses, compared to hospital follow-up. Design Randomised controlled trial. Setting Northern Norway Health Authority Trust, 4 trusts, 11 hospitals and 88 local communities. Participants Patients surgically treated for colon cancer, hospital surgeons and community GPs. Intervention 24-month follow-up according to national guidelines at the community GP office. To ensure a high follow-up guideline adherence, a decision support tool for patients and GPs were used. Main outcome measures Primary outcomes were QoL, measured by the global health scales of the European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ C-30) and EuroQol-5D (EQ-5D). Secondary outcomes were cost-effectiveness and time to cancer diagnoses. Results 110 patients were randomised to intervention (n=55) or control (n=55), and followed by 78 GPs (942 follow-up months) and 70 surgeons (942 follow-up months), respectively. Compared to baseline, there was a significant improvement in postoperative QoL (p=0.003), but no differences between groups were revealed (mean difference at 1, 3, 6, 9, 12, 15, 18, 21 and 24-month follow-up appointments): Global Health; Δ−2.23, p=0.20; EQ-5D index; Δ−0.10, p=0.48, EQ-5D VAS; Δ−1.1, p=0.44. There were no differences in time to recurrent cancer diagnosis (GP 35 days vs surgeon 45 days, p=0.46); 14 recurrences were detected (GP 6 vs surgeon 8) and 7 metastases surgeries performed (GP 3 vs surgeon 4). The follow-up programme initiated 1186 healthcare contacts (GP 678 vs surgeon 508), 1105 diagnostic tests (GP 592 vs surgeon 513) and 778 hospital travels (GP 250 vs surgeon 528). GP organised follow-up was associated with societal cost savings (£8233 vs £9889, p<0.001). Conclusions GP-organised follow-up was associated with no

  19. Denosumab and Bone Metastasis-Free Survival in Men With Castration-Resistant Prostate Cancer: Results of a Global Phase 3, Randomised, Placebo-Controlled Trial

    PubMed Central

    Smith, Matthew R; Saad, Fred; Coleman, Robert; Shore, Neal; Fizazi, Karim; Tombal, Bertrand; Miller, Kurt; Sieber, Paul; Karsh, Lawrence; Damião, Ronaldo; Tammela, Teuvo L; Egerdie, Blair; Van Poppel, Hendrik; Chin, Joseph; Morote, Juan; Gómez-Veiga, Francisco; Borkowski, Tomasz; Ye, Zhishen; Kupic, Amy; Dansey, Roger; Goessl, Carsten

    2013-01-01

    Background Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition may prevent bone metastases. This phase 3 study evaluated denosumab, a fully human anti-RANKL monoclonal antibody, to prevent bone metastasis or death from any cause in men with non-metastatic castration-resistant prostate cancer (CRPC). Methods Men with non-metastatic CRPC at high risk for bone metastasis (PSA ≥8.0 ng/mL and/or PSA doubling time ≤10.0 months) were enrolled in 319 centers from 30 countries. Patients were randomised 1:1 in blinded fashion using an interactive voice response system to receive monthly subcutaneous denosumab 120 mg or placebo. The primary endpoint was bone metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death. Results 1432 patients were randomised, 716 to receive denosumab and 716 to receive placebo. Denosumab significantly increased bone metastasis-free survival by a median of 4.2 months over placebo (hazard ratio 0.85 [0.73–0.98]; P=0.028). Denosumab also significantly delayed time to first bone metastasis (hazard ratio 0.84 [0.71–0.98]; P=0.032). Overall survival was similar between groups (hazard ratio 1.01 [0.85–1.20]; P=0.91). Rates of adverse events (AEs) and serious AEs were generally similar between groups, except for osteonecrosis of jaw (ONJ) and hypocalcemia. Yearly cumulative incidence of ONJ for denosumab was: 1%, 3%, 4% in years 1, 2, 3, respectively; overall, less than 5% (n=33). Hypocalcemia occurred in under 2% (n=12) of denosumab and under 1% (n=2) of placebo patients. The blinded treatment phase has been completed. Conclusion In men with CRPC, denosumab significantly prolonged bone metastasis-free survival and delayed time to bone metastasis. This is the first large randomised study to demonstrate that targeting the bone microenvironment prevents bone metastasis in

  20. Can recombinant human thrombomodulin increase survival among patients with severe septic-induced disseminated intravascular coagulation: a single-centre, open-label, randomised controlled trial

    PubMed Central

    Hagiwara, Akiyoshi; Tanaka, Noriko; Uemura, Tatsuki; Matsuda, Wataru; Kimura, Akio

    2016-01-01

    Objective To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC). Design Single-centre, open-label, randomised controlled trial. Setting Single tertiary hospital. Participant 92 patients with severe septic-induced DIC. Interventions Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. The envelope method was used for randomisation. The treatment group (rhTM group, n=47) was intravenously treated with rhTM within 24 hours of admission (day 0), and the control group (n=45) did not receive any anticoagulants, except in cases of deep venous thrombosis and pulmonary embolism. Primary and secondary measurements Data were collected on days 0 (admission), 1, 2, 3, 5, 7 and 10. The primary outcome was survival at 28 and 90 days. The secondary end points comprised changes in DIC scores, platelet counts, d-dimer, antithrombin III and C reactive protein levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis. Main results The 28-day survival rates were 84% and 83% in the control and rhTM groups, respectively (p=0.745, log-rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p=0.94, log-rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p=0.001, log-rank test). Relative change from baseline of d-dimer levels was significantly lower in the rhTM group than in the control group, on days 3 and 5. Conclusions rhTM treatment decreased d-dimer levels and facilitated DIC recovery in patients with severe septic-induced DIC. However, the treatment did not improve survival in this cohort. Trial registration number UMIN000008339. PMID:28039291

  1. Modafinil for attentional and psychomotor dysfunction in advanced cancer: a double-blind, randomised, cross-over trial.

    PubMed

    Lundorff, L E; Jønsson, B H; Sjøgren, P

    2009-12-01

    Cognitive impairment seems to be highly prevalent in patients with advanced cancer. Modafinil, a novel vigilance and wake-promoting agent, may be an alternative treatment. We wanted to investigate this treatment on attentional and psychomotor dysfunction in cancer patients. 28 cancer patients with a tiredness score of 50 mm or more on a scale of 0 to 10 (0=no tiredness, 10=worst possible tiredness) and Karnofsky Performance Status 40-70 were included. All medications were kept stable during the trial despite short acting opioids for breakthrough pain. On day 1 the patients were randomly assigned to receive 200 mg Modafinil orally or placebo and on day 4 they crossed-over to the alternative treatment. Finger Tapping Test (FTT), Trail Making Test (TMT) and Edmonton Symptom Assessment System (ESAS) were evaluated before tablet intake and again 4, 5 hours after. FTT for the dominant hand as well as TMT were statistically significantly improved on modafinil (p-values=0.006 and 0.042, respectively). On ESAS, depression and drowsiness also improved statistically significantly (p-values=<0.001 and 0.038, respectively). Modafinil in a single dose regimen was significantly superior to placebo regarding two cognitive tests of psychomotor speed and attention. Furthermore subjective scores of depression and drowsiness were significantly improved by modafinil.

  2. Docetaxel versus docetaxel alternating with gemcitabine as treatments of advanced breast cancer: final analysis of a randomised trial

    PubMed Central

    Joensuu, H.; Sailas, L.; Alanko, T.; Sunela, K.; Huuhtanen, R.; Utriainen, M.; Kokko, R.; Bono, P.; Wigren, T.; Pyrhönen, S.; Turpeenniemi-Hujanen, T.; Asola, R.; Leinonen, M.; Hahka-Kemppinen, M.; Kellokumpu-Lehtinen, P.

    2010-01-01

    Background: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. Patients and methods: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. Results: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63–1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). Conclusion: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles. PMID:19819914

  3. A parallel-group, randomised controlled trial of a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners: design and rationale

    PubMed Central

    Lambert, Sylvie D; Girgis, Afaf; McElduff, Patrick; Turner, Jane; Levesque, Janelle V; Kayser, Karen; Mihalopoulos, Cathrine; Shih, Sophy T F; Barker, Daniel

    2013-01-01

    Introduction Coping skills training interventions have been found to be efficacious in helping both patients and their partners manage the physical and emotional challenges they face following a cancer diagnosis. However, many of these interventions are costly and not sustainable. To overcome these issues, a self-directed format is increasingly used. The efficacy of self-directed interventions for patients has been supported; however, no study has reported on the outcomes for their partners. This study will test the efficacy of Coping-Together—a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners. Methods and analysis The proposed three-group, parallel, randomised controlled trial will recruit patients diagnosed in the past 4 months with breast, prostate, colorectal cancer or melanoma through their treating clinician. Patients and their partners will be randomised to (1) a minimal ethical care (MEC) condition—selected Cancer Council New South Wales booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together generic—MEC materials, the six Coping-Together booklets and DVD, the Cancer Council Queensland relaxation audio CD and login to the Coping-Together website or (3) Coping-Together tailored—MEC materials, the Coping-Together DVD, the login to the website and only those Coping-Together booklet sections that pertain to their direct concerns. Anxiety (primary outcome), distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy and dyadic and individual coping will be assessed before receiving the study material (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat and per protocol analysis will be conducted. Ethics and dissemination This study has been approved by the relevant local area health and University ethics committees. Study findings will be disseminated not only through peer-reviewed publications and

  4. A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer. Cuneo Lung Cancer Study Group (CuLCaSG)

    PubMed

    Buccheri, G; Ferrigno, D

    1994-01-01

    Combination chemotherapy with anti-proliferative agents is the usual treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anti-cancer activity of conventional cytotoxic drugs, with no increase of specific toxicity. Following a pilot study of feasibility, we now report the results of a randomised trial evaluating MACC chemotherapy, as originally described, versus the same regimen+LND. 151 patients with advanced NSCLC were assigned at random to the two treatment arms. LND 150 mg was given orally three times daily. Treatment was continued until progression of disease, unacceptable toxicity or refusal by the patient (median number of cycles of MACC, three for both arms; median duration of LND administration, 8 weeks in the arm concerned). Actual dose intensities (DI) of MACC and LND were, respectively, 100 and 83% of those intended (median values). There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient, but no correlation between the duration of treatment with LND and its DI. DIs of LND and MACC were not correlated with each other. In all, 15 objective responses (one complete and four partial responses in the MACC group, 10 partial responses in patients on MACC+LND) were observed. Median progression-free survivals were 20 weeks (confidence interval, CI 14-22) for the group on LND and 17 weeks (CI 12-17) for the control group (non-significant difference). Median overall survivals were, respectively, 30 weeks (CI 23-40) and 27 weeks (CI 22-34), P = non-significant. Toxicity was as expected by the use of MACC, and similar in both arms, except for more severe anaemia and gastric toxicity in the group on MACC+LND. Other uncommon side-effects, seen only in this latter group, were mild to moderate and reversible and included myalgia, asthenia, testicle

  5. Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer.

    PubMed

    Moehler, M; Eimermacher, A; Siebler, J; Höhler, T; Wein, A; Menges, M; Flieger, D; Junginger, T; Geer, T; Gracien, E; Galle, P R; Heike, M

    2005-06-20

    An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

  6. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer.

    PubMed Central

    Powles, T. J.; Jones, A. L.; Judson, I. R.; Hardy, J. R.; Ashley, S. E.

    1991-01-01

    This paper describes a randomised clinical trial in patients with advanced breast cancer, comparing the regimen 3M, mitomycin C 7-8 mg m-2 (day 1), mitozantrone 7-8 mg m-2 (day 1 and 21), methotrexate 35 mg m-2 (day 1 and 21) given on a 42 day cycle with a standard anthracycline containing regimen, VAC, vincristine 1.4 mg m-2 (day 1), anthracycline (adriamycin or epirubicin) 30 mg m-2 (day 1), cyclophosphamide 400 mg m-2 (day 1) given on a 21 day cycle. Of a total of 217 patients, 107 were randomised to 3M and 110 to VAC and a mean of 5.5 courses was given per patient. The overall response rate (complete and partial) was 53% (95% Confidence Limits (CL): 43-62%) for 3M and 49% (CL; 39-58%) for VAC. The response according to sites of metastases was the same for both treatment groups. Symptomatic toxicity including alopecia, neuropathy, vomiting (P less than 0.001) and nausea (P less than 0.01) were significantly less for 3M. Myelosuppression including leucopenia (P less than 0.001) and thrombocytopenia (P less than 0.001) was significantly greater with 3M at day 21, although there was no difference in nadir counts in patients at special risk of myelosuppression and there was no evidence of an increase in infective or bleeding complications. There was no significant difference in the duration of response to 3M (10 months, CL 6-15) and VAC (11 months, CL 7-12), nor in survival (3M, 8 months, CL 6-12; VAC, 10 months, CL 8-12). These results indicate that 3M is as effective as, but has significantly less symptomatic toxicity than, an anthracycline containing regimen for the treatment of advanced breast cancer. PMID:1892775

  7. Future medical applications of single-cell sequencing in cancer

    PubMed Central

    2011-01-01

    Advances in whole genome amplification and next-generation sequencing methods have enabled genomic analyses of single cells, and these techniques are now beginning to be used to detect genomic lesions in individual cancer cells. Previous approaches have been unable to resolve genomic differences in complex mixtures of cells, such as heterogeneous tumors, despite the importance of characterizing such tumors for cancer treatment. Sequencing of single cells is likely to improve several aspects of medicine, including the early detection of rare tumor cells, monitoring of circulating tumor cells (CTCs), measuring intratumor heterogeneity, and guiding chemotherapy. In this review we discuss the challenges and technical aspects of single-cell sequencing, with a strong focus on genomic copy number, and discuss how this information can be used to diagnose and treat cancer patients. PMID:21631906

  8. Future medical applications of single-cell sequencing in cancer.

    PubMed

    Navin, Nicholas; Hicks, James

    2011-05-31

    Advances in whole genome amplification and next-generation sequencing methods have enabled genomic analyses of single cells, and these techniques are now beginning to be used to detect genomic lesions in individual cancer cells. Previous approaches have been unable to resolve genomic differences in complex mixtures of cells, such as heterogeneous tumors, despite the importance of characterizing such tumors for cancer treatment. Sequencing of single cells is likely to improve several aspects of medicine, including the early detection of rare tumor cells, monitoring of circulating tumor cells (CTCs), measuring intratumor heterogeneity, and guiding chemotherapy. In this review we discuss the challenges and technical aspects of single-cell sequencing, with a strong focus on genomic copy number, and discuss how this information can be used to diagnose and treat cancer patients.

  9. Efficacy and safety of lapatinib and trastuzumab for HER2-positive breast cancer: a systematic review and meta-analysis of randomised controlled trials

    PubMed Central

    Xu, Zhi-qiao; Zhang, Yan; Li, Ning; Liu, Pei-jie; Gao, Ling; Gao, Xin; Tie, Xiao-jing

    2017-01-01

    Objectives The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer. Methods Randomised controlled trials (RCTs), published in PubMed, Embase and Web of Science, were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with breast cancer who were treated with lapatinib and trastuzumab. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS) and toxicities. Results were expressed as the risk ratio (RR) or HR with 95% CIs. Pooled estimates were calculated by using a fixed-effects model or a randomised-effects model. Results A total of 7 RCTs involving 2084 patients met the inclusion criteria and were included in this meta-analysis. The combination of lapatinib and trastuzumab significantly improved pCR (RR=1.43, 95% CI 1.23 to 1.67; p<0.001), EFS (HR=0.75, 95% CI 0.60 to 0.93; p=0.009) and OS (HR=0.72, 95% CI 0.56 to 0.93; p=0.011) in the treatment of HER2-positive breast cancer compared with trastuzumab or lapatinib alone. The combination treatment also increased the pCR irrespective of hormone receptor status and tumour size. More frequent grade 3 or 4 adverse events, including diarrhoea, rash or erythema, neutropenia and hepatic adverse events, were found in the combination group than in the trastuzumab or lapatinib group. Conclusions On the basis of the current evidence, our results reveal that the addition of lapatinib to trastuzumab can significantly improve pCR, EFS and OS with a tolerated toxicity in patients with HER2-positive breast

  10. Can an alert in primary care electronic medical records increase participation in a population-based screening programme for colorectal cancer? COLO-ALERT, a randomised clinical trial

    PubMed Central

    2014-01-01

    Background Colorectal cancer is an important public health problem in Spain. Over the last decade, several regions have carried out screening programmes, but population participation rates remain below recommended European goals. Reminders on electronic medical records have been identified as a low-cost and high-reach strategy to increase participation. Further knowledge is needed about their effect in a population-based screening programme. The main aim of this study is to evaluate the effectiveness of an electronic reminder to promote the participation in a population-based colorectal cancer screening programme. Secondary aims are to learn population’s reasons for refusing to take part in the screening programme and to find out the health professionals’ opinion about the official programme implementation and on the new computerised tool. Methods/Design This is a parallel randomised trial with a cross-sectional second stage. Participants: all the invited subjects to participate in the public colorectal cancer screening programme that includes men and women aged between 50–69, allocated to the eleven primary care centres of the study and all their health professionals. The randomisation unit will be the primary care physician. The intervention will consist of activating an electronic reminder, in the patient’s electronic medical record, in order to promote colorectal cancer screening, during a synchronous medical appointment, throughout the year that the intervention takes place. A comparison of the screening rates will then take place, using the faecal occult blood test of the patients from the control and the intervention groups. We will also take a questionnaire to know the opinions of the health professionals. The main outcome is the screening status at the end of the study. Data will be analysed with an intention-to-treat approach. Discussion We expect that the introduction of specific reminders in electronic medical records, as a tool to facilitate

  11. Effects of needs-based patient education on self-efficacy and health outcomes in people with rheumatoid arthritis: a multicentre, single blind, randomised controlled trial

    PubMed Central

    Ndosi, M; Johnson, D; Young, T; Hardware, B; Hill, J; Hale, C; Maxwell, J; Roussou, E; Adebajo, A

    2016-01-01

    Objectives The Educational Needs Assessment Tool (ENAT) is a self-completed questionnaire, which allows patients with arthritis to prioritise their educational needs. The aim of this study was to evaluate the effects of needs-based patient education on self-efficacy, health outcomes and patient knowledge in people with rheumatoid arthritis (RA). Methods Patients with RA were enrolled into this multicentre, single-blind, parallel-group, pragmatic randomised controlled trial. Patients were randomised to either the intervention group (IG) where patients completed ENAT, responses of which were used by the clinical nurse specialist to guide patient education; or control group (CG) in which they received patient education without the use of ENAT. Patients were seen at weeks 0, 16 and 32. The primary outcome was self-efficacy (Arthritis Self Efficacy Scale (ASES)-Pain and ASES-Other symptoms). Secondary outcomes were health status (short form of Arthritis Impact Measurement Scale 2, AIMS2-SF) and patient knowledge questionnaire-RA. We investigated between-group differences using analysis of covariance, adjusting for baseline variables. Results A total of 132 patients were recruited (IG=70 and CG=62). Their mean (SD) age was 54 (12.3) years, 56 (13.3)  years and disease duration 5.2 (4.9) years, 6.7 (8.9) years for IG and CG, respectively. There were significant between-group differences, in favour of IG at week 32 in the primary outcomes, ASES-Pain, mean difference (95% CI) −4.36 (1.17 to 7.55), t=−2.72, p=0.008 and ASES-Other symptoms, mean difference (95% CI) −5.84 (2.07 to 9.62), t=−3.07, p=0.003. In secondary outcomes, the between-group differences favoured IG in AIMS2-SF Symptoms and AIMS2-SF Affect. There were no between-group differences in other secondary outcomes. Conclusions The results suggest that needs-based education helps improve patients’ self-efficacy and some aspects of health status. Trial registration number ISRCTN51523281. PMID:26162769

  12. Efficacy of two injection-site localisation techniques for botulinum toxin injections: a single-blind, crossover, randomised trial protocol among adults with hemiplegia due to stroke

    PubMed Central

    Morel, Claire; Hauret, Isabelle; Andant, Nicolas; Bonnin, Armand; Pereira, Bruno; Coudeyre, Emmanuel

    2016-01-01

    Introduction Botulinum toxin injections are an effective treatment for limb spasticity following stroke. Different tracking techniques are used for this purpose: palpation, electrostimulation, electromyography and ultrasound. Yet very few studies have compared these different techniques, and none has successfully proved the superior efficacy of ultrasound-guided injections compared to another tracking method. The primary objective of our study was therefore to compare the efficacy of botulinum toxin injections depending on the tracking technique used: ultrasound versus electrostimulation. Methods and analysis This is a clinical, single-centre, prospective, interventional, single-blind, crossover, randomised trial. In total, 30 patients aged between 18 and 80 years presenting with triceps surae spasticity (evaluated >1 on the modified Ashworth scale) associated with hemiplegia sequelae due to stroke will be included. The patients will be selected among those who attend for consultation the Physical Medicine and Rehabilitation Department of the Clermont-Ferrand University Hospital. One group will receive the abobotulinumtoxinA (BoNT-A) injection guided by electrostimulation then ultrasound, and the second group's botulinum toxin injections will be guided by ultrasound then electrostimulation. For each patient, the duration of study participation is 5 months. The primary end point is variation in passive ankle dorsiflexion range of motion at slow and high speeds (Tardieu scale) with the knee straight. Ethics and dissemination This study received ethics approval form the CPP of Rhônes-Alpes region. Results will be published in a peer-reviewed journal. Trial registration number NCT01935544; pre-results. PMID:27852706

  13. Photodynamic Therapy Followed by Mohs Micrographic Surgery Compared to Mohs Micrographic Surgery Alone for the Treatment of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised Controlled Trial

    PubMed Central

    Al-Niaimi, Firas; Sheth, Nisith; Kurwa, Habib A; Mallipeddi, Raj

    2015-01-01

    Introduction: Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the “gold standard” treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate. Other treatment modalities used include photodynamic therapy (PDT). Background: We aimed to study the efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size when compared with MMS alone. Materials and Methods: Our study was a single-centre, single-blinded, randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. Results: In the PDT arm, five out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. Conclusion: Our pilot study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this combination therapy. PMID:26157307

  14. Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study

    PubMed Central

    Bajetta, E; Di Bartolomeo, M; Buzzoni, R; Mariani, L; Zilembo, N; Ferrario, E; Lo Vullo, S; Aitini, E; Isa, L; Barone, C; Jacobelli, S; Recaldin, E; Pinotti, G; Iop, A

    2007-01-01

    This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, irinotecan 240 mg m−2 day 1; q21) or TEGAFOX (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, oxaliplatin 120 mg m−2 day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3–4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1–55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6–51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12–23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies. PMID:17245343

  15. Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

    PubMed Central

    Metcalfe, Chris; Avery, Kerry; Berrisford, Richard; Barham, Paul; Noble, Sian M; Fernandez, Aida Moure; Hanna, George; Goldin, Robert; Elliott, Jackie; Wheatley, Timothy; Sanders, Grant; Hollowood, Andrew; Falk, Stephen; Titcomb, Dan; Streets, Christopher; Donovan, Jenny L; Blazeby, Jane M

    2016-01-01

    BACKGROUND Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. OBJECTIVES The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. DESIGN Pilot parallel three-arm randomised controlled trial nested within feasibility work. SETTING Two UK NHS departments of upper gastrointestinal surgery. PARTICIPANTS Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. INTERVENTIONS Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. MAIN OUTCOME MEASURE The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. RESULTS During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the

  16. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

    PubMed Central

    Sebag-Montefiore, David; Stephens, Richard J; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Quirke, Phil; Couture, Jean; de Metz, Catherine; Myint, Arthur Sun; Bessell, Eric; Griffiths, Gareth; Thompson, Lindsay C; Parmar, Mahesh

    2009-01-01

    Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. Methods We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. Findings At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI

  17. The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive–behavioural therapy

    PubMed Central

    Murphy, Glynis H.; Shepstone, Lee; Wilson, Edward C.F.; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

    2016-01-01

    Background There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. Aims To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Method Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. Results The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Conclusions Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703772

  18. Exploring effects of presurgical weight loss among women with stage 0–II breast cancer: protocol for a randomised controlled feasibility trial

    PubMed Central

    Tsuruta, Yuko; Rogers, Laura Q; Krontiras, Helen; Grizzle, William E; Frugé, Andrew D; Oster, Robert A; Umphrey, Heidi R; Jones, Lee W; Azrad, Maria; Demark-Wahnefried, Wendy

    2016-01-01

    Introduction Obesity is a known risk factor for postmenopausal breast cancer and is associated with poorer prognosis for premenopausal and postmenopausal patients; however, the aetiological mechanisms are unknown. Preclinical studies support weight loss via caloric restriction and increased physical activity as a possible cancer control strategy, though few clinical studies have been conducted. We undertook a feasibility trial among women recently diagnosed with stage 0–II breast cancer hypothesising that presurgical weight loss would be feasible, safe and result in favourable changes in tumour markers and circulating biomarkers. Methods and analysis A two-arm randomised controlled trial among 40 overweight or obese women, newly diagnosed with stage 0–II breast cancer and scheduled for surgery was planned. The attention control arm received upper body progressive resistance training and diet counselling to correct deficiencies in nutrient intake; the experimental arm received the same plus counselling on caloric restriction and aerobic exercise to achieve a weight loss of 0.68–0.919 kg/week. In addition to achieving feasibility benchmarks (accruing and retaining at least 80% of participants, and observing no serious adverse effects attributable to the intervention), we will explore the potential impact of an acute state of negative energy balance on tumour proliferation rates (Ki-67), as well as other tumour markers, serum biomarkers, gene expression, microbiome profiles and other clinical outcomes (eg, quality of life). Outcomes for the 2 study arms are compared using mixed models repeated-measures analyses. Ethics and dissemination Ethics approval was received from the University of Alabama at Birmingham Institutional Review Board (Protocol number F130325009). Study findings will be disseminated through peer-reviewed publications. Given that this is one of the first studies to investigate the impact of negative energy balance directly on tumour biology in

  19. Is referral of postsurgical colorectal cancer survivors to cardiac rehabilitation feasible and acceptable? A pragmatic pilot randomised controlled trial with embedded qualitative study

    PubMed Central

    Hubbard, Gill; Adams, Richard; Campbell, Anna; Kidd, Lisa; Leslie, Stephen J; Munro, Julie; Watson, Angus

    2016-01-01

    Objectives (1) Assess whether cardiac rehabilitation (CR) is a feasible and acceptable model of rehabilitation for postsurgical colorectal cancer (CRC) survivors, (2) evaluate trial procedures. This article reports the results of the first objective. Design and setting A pragmatic pilot randomised controlled trial with embedded qualitative study was conducted in 3 UK hospitals with CR facilities. Descriptive statistics were used to summarise trial parameters indicative of intervention feasibility and acceptability. Interviews and focus groups were conducted and data analysed thematically. Participants People with CRC were considered for inclusion in the trial if they were ≥18 years old, diagnosed with primary CRC and in the recovery period postsurgery (they could still be receiving adjuvant therapy). 31% (n=41) of all eligible CRC survivors consented to participate in the trial. 22 of these CRC survivors, and 8 people with cardiovascular disease (CVD), 5 CRC nurses and 6 CR clinicians participated in the qualitative study. Intervention Referral of postsurgical CRC survivors to weekly CR exercise classes and information sessions. Classes included CRC survivors and people with CVD. CR nurses and physiotherapists were given training about cancer and exercise. Results Barriers to CR were protracted recoveries from surgery, ongoing treatments and poor mobility. No adverse events were reported during the trial, suggesting that CR is safe. 62% of participants completed the intervention as per protocol and had high levels of attendance. 20 health professionals attended the cancer and exercise training course, rating it as excellent. Participants perceived that CR increased CRC survivors’ confidence and motivation to exercise, and offered peer support. CR professionals were concerned about CR capacity to accommodate cancer survivors and their ability to provide psychosocial support to this group of patients. Conclusions CR is feasible and acceptable for postsurgical

  20. Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial

    PubMed Central

    Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S.; Campbell, Iain C.; Schmidt, Ulrike

    2017-01-01

    Background Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. Objective This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Methods Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. Results AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. Conclusions These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN. PMID:28121991

  1. Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial

    PubMed Central

    2010-01-01

    Background Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355 000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made. Methods To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems. Results The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention × age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems. Conclusions This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and

  2. Matter Over Mind: A Randomised-Controlled Trial of Single-Session Biofeedback Training on Performance Anxiety and Heart Rate Variability in Musicians

    PubMed Central

    Wells, Ruth; Outhred, Tim; Heathers, James A. J.; Quintana, Daniel S.; Kemp, Andrew H.

    2012-01-01

    Background Musical performance is a skilled activity performed under intense pressure, thus is often a profound source of anxiety. In other contexts, anxiety and its concomitant symptoms of sympathetic nervous system arousal have been successfully ameliorated with HRV biofeedback (HRV BF), a technique involving slow breathing which augments autonomic and emotional regulatory capacity. Objective: This randomised-controlled study explored the impact of a single 30-minute session of HRV BF on anxiety in response to a highly stressful music performance. Methods A total of 46 trained musicians participated in this study and were randomly allocated to a slow breathing with or without biofeedback or no-treatment control group. A 3 Group×2 Time mixed experimental design was employed to compare the effect of group before and after intervention on performance anxiety (STAI-S) and frequency domain measures of HRV. Results Slow breathing groups (n = 30) showed significantly greater improvements in high frequency (HF) and LF/HF ratio measures of HRV relative to control (n = 15) during 5 minute recordings of performance anticipation following the intervention (effect size: η2 = 0.122 and η2 = 0.116, respectively). The addition of biofeedback to a slow breathing protocol did not produce differential results. While intervention groups did not exhibit an overall reduction in self-reported anxiety, participants with high baseline anxiety who received the intervention (n = 15) displayed greater reductions in self-reported state anxiety relative to those in the control condition (n = 7) (r = 0.379). Conclusions These findings indicate that a single session of slow breathing, regardless of biofeedback, is sufficient for controlling physiological arousal in anticipation of psychosocial stress associated with music performance and that slow breathing is particularly helpful for musicians with high levels of anxiety. Future research is needed to further

  3. Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

    PubMed Central

    Mochiki, E; Ogata, K; Ohno, T; Toyomasu, Y; Haga, N; Fukai, Y; Aihara, R; Ando, H; Uchida, N; Asao, T; Kuwano, H

    2012-01-01

    Background: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. Methods: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1–14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1–21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. Conclusion: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. PMID:22617130

  4. A single-molecule view of gene regulation in cancer

    NASA Astrophysics Data System (ADS)

    Larson, Daniel

    2013-03-01

    Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. Steroid receptors coordinate a diverse range of responses in higher eukaryotes and are involved in a wide range of human diseases, including cancer. Steroid receptor response elements are present throughout the human genome and modulate chromatin remodeling and transcription in both a local and long-range fashion. As such, steroid receptor-mediated transcription is a paradigm of genetic control in the metazoan nucleus. Moreover, the ligand-dependent nature of these transcription factors makes them appealing targets for therapeutic intervention, necessitating a quantitative understanding of how receptors control output from target genes. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single gene and follow dynamic synthesis of RNA from the activated locus. The response delay is a measure of time required for chromatin remodeling at a single gene.

  5. Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): SYNCHRONOUS - a randomised controlled multicentre trial (ISRCTN30964555)

    PubMed Central

    2012-01-01

    Background Currently, it remains unclear, if patients with colon cancer and synchronous unresectable metastases who present without severe symptoms should undergo resection of the primary tumour prior to systemic chemotherapy. Resection of the primary tumour may be associated with significant morbidity and delays the beginning of chemotherapy. However, it may prevent local symptoms and may, moreover, prolong survival as has been demonstrated in patients with metastatic renal cell carcinoma. It is the aim of the present randomised controlled trial to evaluate the efficacy of primary tumour resection prior to systemic chemotherapy to prolong survival in patients with newly diagnosed colon cancer who are not amenable to curative therapy. Methods/design The SYNCHRONOUS trial is a multicentre, randomised, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases are eligible for inclusion. Exclusion criteria are primary tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumour as well as systemic chemotherapy is provided according to the standards of the participating institution. The primary endpoint is overall survival that is assessed with a minimum follow-up of 36 months. Furthermore, it is the objective of the trial to assess the safety of both treatment strategies as well as quality of life. Discussion The SYNCHRONOUS trial is a multicentre, randomised, controlled trial to assess the efficacy and safety of primary tumour resection before beginning of systemic chemotherapy in patients with metastatic colon cancer not amenable to curative therapy. Trial registration ISRCTN30964555 PMID:22480173

  6. Lavandula angustifolia Mill. Oil and Its Active Constituent Linalyl Acetate Alleviate Pain and Urinary Residual Sense after Colorectal Cancer Surgery: A Randomised Controlled Trial

    PubMed Central

    Yu, So Hyun

    2017-01-01

    Pain and urinary symptoms following colorectal cancer (CRC) surgery are frequent and carry a poor recovery. This study tested the effects of inhalation of Lavandula angustifolia Mill. (lavender) oil or linalyl acetate on pain relief and lower urinary tract symptoms (LUTS) following the removal of indwelling urinary catheters from patients after CRC surgery. This randomised control study recruited 66 subjects with indwelling urinary catheters after undergoing CRC surgery who later underwent catheter removal. Patients inhaled 1% lavender, 1% linalyl acetate, or vehicle (control group) for 20 minutes. Systolic and diastolic blood pressure (BP), heart rate, LUTS, and visual analog scales of pain magnitude and quality of life (QoL) regarding urinary symptoms were measured before and after inhalation. Systolic BP, diastolic BP, heart rate, LUTS, and QoL satisfaction with urinary symptoms were similar in the three groups. Significant differences in pain magnitude and urinary residual sense of indwelling catheters were observed among the three groups, with inhalation of linalyl acetate being significantly more effective than inhalation of lavender or vehicle. Inhalation of linalyl acetate is an effective nursing intervention to relieve pain and urinary residual sense of indwelling urinary catheters following their removal from patients who underwent CRC surgery. PMID:28154606

  7. Quantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer.

    PubMed

    Bernhard, J; Zahrieh, D; Coates, A S; Gelber, R D; Castiglione-Gertsch, M; Murray, E; Forbes, J F; Perey, L; Collins, J; Snyder, R; Rudenstam, C-M; Crivellari, D; Veronesi, A; Thürlimann, B; Fey, M F; Price, K N; Goldhirsch, A; Hürny, C

    2004-11-29

    We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.

  8. Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases.

    PubMed

    Watson, Henry; Cockbain, Andrew J; Spencer, Jade; Race, Amanda; Volpato, Milene; Loadman, Paul M; Toogood, Giles J; Hull, Mark A

    2016-12-01

    We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of 'contamination' in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16-0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients.

  9. LIHNCS - Lugol’s iodine in head and neck cancer surgery: a multicentre, randomised controlled trial assessing the effectiveness of Lugol’s iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in situ at mucosal resection margins of oral and oropharyngeal squamous cell carcinoma: study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Oral cavity and oropharynx cancer are increasing in incidence worldwide but survival outcomes have not significantly improved over the last three decades. The presence of dysplasia or carcinoma in situ at surgical margins following resection of squamous carcinoma of the mucosal surfaces of the head and neck has been shown to be associated with a higher incidence of local recurrence and reduced survival. While invasive carcinoma in mucosal surfaces can usually be distinguished from adjacent normal mucous membrane, pre-malignant disease is much less readily distinguished at operation. We describe a protocol for a randomised, controlled trial in which we will assess the effectiveness of Lugol’s iodine staining in allowing visualisation and excision of cancer margin dysplasia at time of primary surgery. Methods/Design We will recruit 300 patients diagnosed with oral cavity or oropharynx squamous cell carcinoma. All participants will be planned for primary surgery with curative intent. After completion of baseline assessment participants will be randomised into either a standard surgical treatment arm or surgical treatment including Lugol’s iodine staining. Discussion This paper describes the rationale and design of a unique trial in head and neck surgical oncology. If margin dysplasia visualisation with Lugol’s iodine allows complete excision of high-risk, pre-cancer mucosa at time of primary surgery, this may lead to a reduction in local recurrence and improved survival. Trial registration Current Controlled Trials ISRCTN03712770. PMID:24063578

  10. Rapid effect of single-dose rosiglitazone treatment on endothelial function in healthy men with normal glucose tolerance: data from a randomised, placebo-controlled, double-blind study.

    PubMed

    Walcher, Thomas; Walcher, Daniel; Hetzel, Jürgen; Mielke, Catrin; Rau, Matthias; Rittig, Kilian; Balletshofer, Bernd; Schwedhelm, Edzard; Hombach, Vinzenz; Böger, Rainer H; Koenig, Wolfgang; Marx, Nikolaus

    2010-07-01

    Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h from 4.3% (3.3; 4.9) to 7.6% (5.6; 9.2) (p<0.0001 vs. baseline) resulting in a highly significant effect compared with placebo (p<0.0001 for difference between groups). After 24 h FMD was still significantly higher in the rosiglitazone group compared with baseline (p=0.001), but the effect was no longer statistically significant versus placebo (p=0.171). Our study shows a very rapid effect of single dose rosiglitazone treatment on endothelial function in non-diabetic healthy men, underscoring the hypothesis that TZDs may exhibit direct effect in the vasculature independent of their metabolic action.

  11. A randomised crossover trial comparing a single-use polyvinyl chloride laryngeal mask airway with a single-use silicone laryngeal mask airway.

    PubMed

    Bell, S F; Morris, N G; Rao, A; Wilkes, A R; Goodwin, N

    2012-12-01

    We compared insertion rates of single-use polyvinyl chloride laryngeal mask airways (LMAs) vs single-use silicone LMAs in 72 anaesthetised patients. Both airways were produced by Flexicare Medical. Laryngeal mask airway insertion was successful on the first attempt in 68/72 (94%) polyvinyl chloride LMAs vs 64/72 (89%) silicone LMAs (p = 0.39). Overall insertion rates were 72/72 (100%) for the polyvinyl chloride LMAs and 71/72 (99%) for the silicone LMAs (p = 1.0). Mean (SD) insertion times were similar for polyvinyl chloride and silicone LMAs: 24.3 (5.1)s vs 24.8 (7.8)s (p = 0.64). Laryngeal mask airway position, as assessed using a fibrescope, was not different (p = 0.077). The median (IQR [range]) leak pressure was 16 (12-20 [6-30]) cmH(2) O for the polyvinyl LMA and 18 (13-22 [6-30]) cmH(2) O or the silicone LMA (p = 0.037). In conclusion, we did not find any important differences between polyvinyl chloride and silicone laryngeal mask airways.

  12. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M; Protheroe, Andrew; Sheehan, Denise; Srihari, Narayanan; Parmar, Mahesh KB

    2012-01-01

    Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A). Methods Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544. Findings 2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly

  13. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

    PubMed

    Palmieri, C; Cleator, S; Kilburn, L S; Kim, S B; Ahn, S-H; Beresford, M; Gong, G; Mansi, J; Mallon, E; Reed, S; Mousa, K; Fallowfield, L; Cheang, M; Morden, J; Page, K; Guttery, D S; Rghebi, B; Primrose, L; Shaw, J A; Thompson, A M; Bliss, J M; Coombes, R C

    2014-12-01

    Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

  14. Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials

    PubMed Central

    Wardle, Jane; von Wagner, Christian; Kralj-Hans, Ines; Halloran, Stephen P; Smith, Samuel G; McGregor, Lesley M; Vart, Gemma; Howe, Rosemary; Snowball, Julia; Handley, Graham; Logan, Richard F; Rainbow, Sandra; Smith, Steve; Thomas, Mary C; Counsell, Nicholas; Morris, Steve; Duffy, Stephen W; Hackshaw, Allan; Moss, Sue; Atkin, Wendy; Raine, Rosalind

    2016-01-01

    Summary Background Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. Methods All people eligible for screening (men and women aged 60–74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July–August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. Findings As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163 525) and 2 (n=150 417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04–1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04–1·20, p=0·003) than in the least deprived (1·00, 0·94–1·06, p=0·98). Overall uptake was also increased (1·07, 1·03–1·11, p=0·001). Interpretation Of four evidence

  15. Effect of aerobic exercise and relaxation training on fatigue and physical performance of cancer patients after surgery. A randomised controlled trial.

    PubMed

    Dimeo, Fernando C; Thomas, Frank; Raabe-Menssen, Cornelia; Pröpper, Felix; Mathias, Michael

    2004-11-01

    Fatigue is a frequent problem after surgical treatment of solid tumours. Aerobic exercise and psychosocial interventions have been shown to reduce the severity of this symptom in cancer patients. Therefore, we compared the effect of the two therapies on fatigue in a randomised controlled study. Seventy-two patients who underwent surgery for lung (n=27) or gastrointestinal tumours (n=42) were assigned to an aerobic exercise group (stationary biking 30 min five times weekly) or a progressive relaxation training group (45 min three times per week). Both interventions were carried out for 3 weeks. At the beginning and the end of the study, we evaluated physical, cognitive and emotional status and somatic complaints with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC-QLQ-30) questionnaire, and maximal physical performance with an ergometric stress test. Physical performance of the training group improved significantly during the programme (9.4+/-20 watts, p=0.01) but remained unchanged in the relaxation group (1.5+/-14.8 watts, p=0.37). Fatigue and global health scores improved in both groups during the intervention (fatigue: training group 21%, relaxation group 19%; global health of both groups 19%, p for all < or =0.01); however, there was no significant difference between changes in the scores of both groups (p=0.67). We conclude that a structured aerobic training programme improves the physical performance of patients recovering from surgery for solid tumours. However, exercise is not better than progressive relaxation training for the treatment of fatigue in this setting.

  16. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).

    PubMed Central

    Vaidya, Jayant S; Wenz, Frederik; Bulsara, Max; Tobias, Jeffrey S; Joseph, David J; Saunders, Christobel; Brew-Graves, Chris; Potyka, Ingrid; Morris, Stephen; Vaidya, Hrisheekesh J; Williams, Norman R; Baum, Michael

    2016-01-01

    BACKGROUND Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies. OBJECTIVE To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks. DESIGN The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world. SETTING Thirty-three centres in 11 countries. PARTICIPANTS Women who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size. INTERVENTIONS TARGIT within a risk-adapted approach and whole-breast EBRT. MAIN OUTCOME MEASURES The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer

  17. Single-Cell-Precision Microplasma-Induced Cancer Cell Apoptosis

    PubMed Central

    Lu, Xinpei; He, Guangyuan; Ostrikov, Kostya

    2014-01-01

    The issue of single-cell control has recently attracted enormous interest. However, in spite of the presently achievable intracellular-level physiological probing through bio-photonics, nano-probe-based, and some other techniques, the issue of inducing selective, single-cell-precision apoptosis, without affecting neighbouring cells remains essentially open. Here we resolve this issue and report on the effective single-cell-precision cancer cell treatment using the reactive chemistry of the localized corona-type plasma discharge around a needle-like electrode with the spot size ∼1 µm. When the electrode is positioned with the micrometer precision against a selected cell, a focused and highly-localized micro-plasma discharge induces apoptosis in the selected individual HepG2 and HeLa cancer cells only, without affecting any surrounding cells, even in small cell clusters. This is confirmed by the real-time monitoring of the morphological and structural changes at the cellular and cell nucleus levels after the plasma exposure. PMID:24971517

  18. Single incision glove port laparoscopic colorectal cancer resection

    PubMed Central

    Joshi, HMN; Gosselink, MP; Adusumilli, S; Hompes, R; Cunningham, C; Lindsey, I

    2015-01-01

    Introduction The advantages of single port surgery remain controversial. This study was designed to evaluate the safety and feasibility of single incision glove port colon resections using a diathermy hook, reusable ports and standard laparoscopic straight instrumentation. Methods Between June 2012 and February 2014, 70 consecutive patients (30 women) underwent a colonic resection using a wound retractor and glove port. Forty patients underwent a right hemicolectomy through the umbilicus and thirty underwent attempted single port resection via an incision in the right rectus sheath (14 high anterior resection, 13 low anterior resection, 3 abdominoperineal resection). Results Sixty-two procedures (89%) were completed without conversion to open or multiport techniques. Four procedures had to be converted and additional ports were needed in four other patients. The postoperative mortality rate was 0%. Complications occurred in six patients (9%). Two cases were R1 while the remainder were R0 with a median nodal harvest of 20 (range: 9–48). The median length of hospital stay was 5 days (range: 3–25 days) (right hemicolectomy: 5 days (range: 3–12 days), left sided resection: 6 days (range: 4–25 days). At a median follow-up of 14 months, no port site hernias were observed. Conclusions Single incision glove port surgery is an appropriate technique for different colorectal cancer resections and has the advantage of being less expensive than surgery with commercial single incision ports. PMID:26263805

  19. Single molecule targeted sequencing for cancer gene mutation detection

    PubMed Central

    Gao, Yan; Deng, Liwei; Yan, Qin; Gao, Yongqian; Wu, Zengding; Cai, Jinsen; Ji, Daorui; Li, Gailing; Wu, Ping; Jin, Huan; Zhao, Luyang; Liu, Song; Ge, Liangjin; Deem, Michael W.; He, Jiankui

    2016-01-01

    With the rapid decline in cost of sequencing, it is now affordable to examine multiple genes in a single disease-targeted clinical test using next generation sequencing. Current targeted sequencing methods require a separate step of targeted capture enrichment during sample preparation before sequencing. Although there are fast sample preparation methods available in market, the library preparation process is still relatively complicated for physicians to use routinely. Here, we introduced an amplification-free Single Molecule Targeted Sequencing (SMTS) technology, which combined targeted capture and sequencing in one step. We demonstrated that this technology can detect low-frequency mutations using artificially synthesized DNA sample. SMTS has several potential advantages, including simple sample preparation thus no biases and errors are introduced by PCR reaction. SMTS has the potential to be an easy and quick sequencing technology for clinical diagnosis such as cancer gene mutation detection, infectious disease detection, inherited condition screening and noninvasive prenatal diagnosis. PMID:27193446

  20. Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial

    PubMed Central

    Saposnik, Gustavo; Cohen, Leonardo G; Mamdani, Muhammad; Pooyania, Sepideth; Ploughman, Michelle; Cheung, Donna; Shaw, Jennifer; Hall, Judith; Nord, Peter; Dukelow, Sean; Nilanont, Yongchai; De los Rios, Felipe; Olmos, Lisandro; Levin, Mindy; Teasell, Robert; Cohen, Ashley; Thorpe, Kevin; Laupacis, Andreas; Bayley, Mark

    2016-01-01

    Summary Background Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. Methods In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18–85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. Findings The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group

  1. Single-cell mutational profiling and clonal phylogeny in cancer

    PubMed Central

    Potter, Nicola E.; Ermini, Luca; Papaemmanuil, Elli; Cazzaniga, Giovanni; Vijayaraghavan, Gowri; Titley, Ian; Ford, Anthony; Campbell, Peter; Kearney, Lyndal; Greaves, Mel

    2013-01-01

    The development of cancer is a dynamic evolutionary process in which intraclonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intraclonal genetic architectures have major implications for biopsy-based prognosis and for targeted therapy. High-depth, next-generation sequencing (NGS) efficiently captures the mutational load of individual tumors or biopsies. But, being a snapshot portrait of total DNA, it disguises the fundamental features of subclonal variegation of genetic lesions and of clonal phylogeny. Single-cell genetic profiling provides a potential resolution to this problem, but methods developed to date all have limitations. We present a novel solution to this challenge using leukemic cells with known mutational spectra as a tractable model. DNA from flow-sorted single cells is screened using multiplex targeted Q-PCR within a microfluidic platform allowing unbiased single-cell selection, high-throughput, and comprehensive analysis for all main varieties of genetic abnormalities: chimeric gene fusions, copy number alterations, and single-nucleotide variants. We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies. PMID:24056532

  2. Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy

    PubMed Central

    Courneya, K S; McKenzie, D C; Mackey, J R; Gelmon, K; Friedenreich, C M; Yasui, Y; Reid, R D; Vallerand, J R; Adams, S C; Proulx, C; Dolan, L B; Wooding, E; Segal, R J

    2014-01-01

    Background: The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. Methods: Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25–30 min of aerobic exercise, a higher dose of 50–60 min of aerobic exercise, or a higher dose of 50–60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. Results: Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. Conclusions: Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions. PMID:25144625

  3. Randomised Phase II Trial (NCT00637975) Evaluating Activity and Toxicity of Two Different Escalating Strategies for Pregabalin and Oxycodone Combination Therapy for Neuropathic Pain in Cancer Patients

    PubMed Central

    Garassino, Marina Chiara; Piva, Sheila; La Verde, Nicla; Spagnoletti, Ilaria; Iorno, Vittorio; Carbone, Claudia; Febbraro, Antonio; Bianchi, Anna; Bramati, Annalisa; Moretti, Anna; Ganzinelli, Monica; Marabese, Mirko; Gentili, Marta; Torri, Valter; Farina, Gabriella

    2013-01-01

    Purpose Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy. Methods Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration ClinicalTrials.gov NCT00637975 PMID:23577077

  4. First-line non-cytotoxic therapy in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of 10 randomised clinical trials.

    PubMed

    Poorthuis, Michiel H F; Vernooij, Robin W M; van Moorselaar, R Jeroen A; de Reijke, Theo M

    2017-01-06

    The aim of this study is to systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, EMBASE, and the Cochrane libraries up to 1 March 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated. We assessed the risk of bias with the Cochrane Collaboration's tool and graded the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach. We included 25 articles, reporting on 10 unique RCTs describing seven different comparisons. In one RCT, a prolonged OS and PFS (high quality) were found with abiraterone and prednisone compared to placebo plus prednisone. In one RCT, a prolonged OS and PFS (high quality) were found with enzalutamide compared to placebo. In two RCTs, a prolonged OS (high and moderate quality) was found with (223) radium compared to placebo, but its effect on PFS is unknown. In three RCTs, a prolonged OS (moderate quality) was found with sipuleucel-T compared to placebo, but no prolonged PFS (low quality). In one RCT a prolonged PFS (high quality) was found with orteronel compared to placebo, but no prolonged OS (moderate quality). In one RCT, a prolonged OS (moderate quality) was found with bicalutamide compared to placebo, but its effect on PFS is unknown. In one RCT, a prolonged PFS (high quality) was found with enzalutamide compared to bicalutamide, but its effect on OS is unknown. The best evidence was found for abiraterone and enzalutamide for effective prolongation of OS and PFS to treat chemotherapy-naive patients with mCRPC. However, taking both QoL and AEs into consideration, other treatment modalities could be considered for individual patients.

  5. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  6. Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

    PubMed Central

    Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

    2015-01-01

    Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

  7. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0234 TITLE: Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...single cell RNA sequencing on airway epithelial cells obtained from smokers with and without lung cancer to identify cell-type dependent gene expression

  8. Comparative effectiveness of chemopreventive interventions for colorectal cancer: protocol for a systematic review and network meta-analysis of randomised controlled trials

    PubMed Central

    Veettil, Sajesh K.; Saokaew, Surasak; Lim, Kean Ghee; Ching, Siew Mooi; Phisalprapa, Pochamana

    2016-01-01

    Background Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with substantial socioeconomic burden. Despite considerable research, including numerous randomised controlled trials (RCTs) and systematic reviews assessed the effect of various chemopreventive interventions for CRC, there remains uncertainty regarding the comparative effectiveness of these agents. No network meta-analytic study has been published to evaluate the efficacies of these agents for CRC. Therefore, the aim of this study is to summarise the direct and indirect evidence for these interventions to prevent CRC in average-high risk individuals, and to rank these agents for practical consideration. Methods We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. Results This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA-compliant guideline. The results of this systematic review and

  9. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial

    PubMed Central

    Dobs, Adrian S; Boccia, Ralph V; Croot, Christopher C; Gabrail, Nashat Y; Dalton, James T; Hancock, Michael L; Johnston, Mary A; Steiner, Mitchell S

    2016-01-01

    Summary Background Cancer-induced muscle wasting begins early in the course of a patient's malignant disease, resulting in declining physical function and other detrimental clinical consequences. This randomised, double-blind, placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm, a selective androgen receptor modulator, in patients with cancer. Methods We enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days at US and Argentinian oncology clinics. The sponsor, study personnel, and participants were masked to assignment. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry. Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol-specified window of within 10 days before baseline or first study drug, and within 10 days of day 113 or end of study (evaluable efficacy population). Adverse events and other safety measurements were assessed in the intention-to-treat (safety) population. This trial is registered with ClinicalTrials.gov, number NCT00467844. Findings Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1·5 kg, range −2·1 to 12·6, p=0·0012; enodosarm 3 mg 1·0 kg, −4·8 to 11·5, p=0·046). Change in

  10. Intraoperative Radiotherapy for Parotid Cancer: A Single-Institution Experience

    SciTech Connect

    Zeidan, Youssef H.; Shiue, Kevin; Weed, Daniel; Johnstone, Peter A.; Terry, Colin; Freeman, Stephen; Krowiak, Edward; Borrowdale, Robert; Huntley, Tod; Yeh, Alex

    2012-04-01

    Purpose: Our practice policy has been to provide intraoperative radiotherapy (IORT) at resection to patients with head-and-neck malignancies considered to be at high risk of recurrence. The purpose of the present study was to review our experience with the use of IORT for primary or recurrent cancer of the parotid gland. Methods and Materials: Between 1982 and 2007, 96 patients were treated with gross total resection and IORT for primary or recurrent cancer of the parotid gland. The median age was 62.9 years (range, 14.3-88.1). Of the 96 patients, 33 had previously undergone external beam radiotherapy as a component of definitive therapy. Also, 34 patients had positive margins after surgery, and 40 had perineural invasion. IORT was administered as a single fraction of 15 or 20 Gy with 4-6-MeV electrons. The median follow-up period was 5.6 years. Results: Only 1 patient experienced local recurrence, 19 developed regional recurrence, and 12 distant recurrence. The recurrence-free survival rate at 1, 3, and 5 years was 82.0%, 68.5%, and 65.2%, respectively. The 1-, 3-, and 5-year overall survival rate after surgery and IORT was 88.4%, 66.1%, and 56.2%, respectively. No perioperative fatalities occurred. Complications developed in 26 patients and included vascular complications in 7, trismus in 6, fistulas in 4, radiation osteonecrosis in 4, flap necrosis in 2, wound dehiscence in 2, and neuropathy in 1. Of these 26 patients, 12 had recurrent disease, and 8 had undergone external beam radiotherapy before IORT. Conclusions: IORT results in effective local disease control at acceptable levels of toxicity and should be considered for patients with primary or recurrent cancer of the parotid gland.

  11. An art therapy intervention for cancer patients in the ambulant aftercare - results from a non-randomised controlled study.

    PubMed

    Geue, K; Richter, R; Buttstädt, M; Brähler, E; Singer, S

    2013-05-01

    Art therapy in psycho-oncology is gaining increasing importance, but systematic evaluations of its effects are rare. The aim of this study is to investigate the effects of an art therapy intervention for cancer patients in ambulant aftercare on psychological distress and coping. The intervention consisted of 22 sessions. At three points of measurement (t1: before intervention, t2: following intervention, t3: 6 months after t2), participants responded to questionnaires (Freiburg Questionnaire on Coping with Illness, Perceived Adjustment to Chronic Illness Scale, Hospital Anxiety and Depression Scale). A group of haemato-oncological patients served as the comparison group (CG). Pre-post comparisons and analyses of variance were applied for statistical analysis. Relevant confounders were controlled. Fifty-four patients (intervention group, IG) with various cancer diagnoses completed the intervention. One hundred and twenty-nine data sets were available for the CG. Analyses of variance included group membership (IG vs. CG) and the following factors: gender, other psychosocial help and major life events. None of these variables was a predictor for changes in depression, anxiety and coping. Therefore, we could not prove intervention effects over time. Our results contradict those of preliminary studies and raise important questions. Further work on evaluating art therapy is necessary to explore which intervention concepts in which setting at which treatment stage show significant effects. Therefore, controlling for relevant confounders is needed.

  12. Randomised phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

    PubMed

    Kwakman, J J M; Simkens, L H J; van Rooijen, J M; van de Wouw, A J; Ten Tije, A J; Creemers, G J M; Hendriks, M P; Los, M; van Alphen, R J; Polée, M B; Muller, E W; van der Velden, A M T; van Voorthuizen, T; Koopman, M; Mol, L; van Werkhoven, E; Punt, C J A

    2017-04-05

    Hand-foot syndrome (HFS) is a common side effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients.

  13. A randomised, multicentre clinical trial of specialised palliative care plus standard treatment versus standard treatment alone for cancer patients with palliative care needs: the Danish palliative care trial (DanPaCT) protocol

    PubMed Central

    2013-01-01

    Background Advanced cancer patients experience considerable symptoms, problems, and needs. Early referral of these patients to specialised palliative care (SPC) could improve their symptoms and problems. The Danish Palliative Care Trial (DanPaCT) investigates whether patients with metastatic cancer, who report palliative needs in a screening, will benefit from being referred to ‘early SPC’. Methods/Design DanPaCT is a clinical, multicentre, parallel-group superiority trial with balanced randomisation (1:1). The planned sample size is 300 patients. Patients are randomised to specialised palliative care (SPC) plus standard treatment versus standard treatment. Consecutive patients from oncology departments are screened for palliative needs with a questionnaire if they: a) have metastatic cancer; b) are 18 years or above; and c) have no prior contact with SPC. Patients with palliative needs (i.e. symptoms/problems exceeding a certain threshold) according to the questionnaire are eligible. The primary outcome is the change in the patients’ primary need (the most severe symptom/problem measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Secondary outcomes are other symptoms/problems (EORTC QLQ-C30), satisfaction with health care (FAMCARE P-16), anxiety and depression (the Hospital Anxiety and Depression scale), survival, and health care costs. Discussion Only few trials have investigated the effects of SPC. To our knowledge DanPaCT is the first trial to investigate screening based ‘early SPC’ for patients with a broad spectrum of cancer diagnosis. Trial registration Current controlled Trials NCT01348048 PMID:24152880

  14. The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only

    PubMed Central

    Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

    2015-01-01

    Background Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Methods Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score <9 (original definition), or GCS<13 and an Abbreviated Injury Scale score for the head region ≥3 (modified definition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. Results 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), p<0.01, Number needed to treat =6. 338 patients met the modified definition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. Conclusions This trial suggests a potential mortality reduction in patients with blunt trauma with GCS<9 receiving additional physician care (original definition only). Confirmatory studies which also address non-compliance issues are needed. Trial registration number NCT00112398. PMID:25795741

  15. Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation

    PubMed Central

    Bensdorp, A J; Tjon-Kon-Fat, R I; Bossuyt, P M M; Koks, C A M; Oosterhuis, G J E; Hoek, A; Hompes, P G A; Broekmans, F J M; Verhoeve, H R; de Bruin, J P; van Golde, R; Repping, S; Cohlen, B J; Lambers, M D A; van Bommel, P F; Slappendel, E; Perquin, D; Smeenk, J M; Pelinck, M J; Gianotten, J; Hoozemans, D A; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W J

    2015-01-01

    Objectives To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting 17 centres in the Netherlands. Participants Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval

  16. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    PubMed Central

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  17. Acute effects of traditional Thai massage on cortisol levels, arterial blood pressure and stress perception in academic stress condition: A single blind randomised controlled trial.

    PubMed

    Bennett, Surussawadi; Bennett, Michael John; Chatchawan, Uraiwon; Jenjaiwit, Patcharaporn; Pantumethakul, Rungthip; Kunhasura, Soontorn; Eungpinichpong, Wichai

    2016-04-01

    Traditional Thai massage (TTM) has been applied widely to promote relaxation. However, there is little evidence to support its efficacy on academic stress. A randomised controlled trial was performed to examine the acute effects of TTM on cortisol level, blood pressure, heart rate and stress perception in academic stress. This prospective trial included 36 physiotherapy students with a self perceived stress score of between 3 and 5. They were randomly allocated into the TTM (18 people) group or the control group (18 people). Saliva cortisol level, blood pressure, heart rate and stress perception rating were measured before and after the intervention. Both groups showed a significant reduction in cortisol level and heart rate when compared with baseline (p < 0.001). There were no significant differences in cortisol level between the two groups. The results suggest the need for further study into other possible physiological effects on stress of TTM.

  18. Overall survival benefit with pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer in CLEOPATRA, a randomised Phase 3 study

    PubMed Central

    Swain, Sandra M.; Kim, Sung-Bae; Cortés, Javier; Ro, Jungsil; Semiglazov, Vladimir; Campone, Mario; Ciruelos, Eva; Ferrero, Jean-Marc; Schneeweiss, Andreas; Knott, Adam; Clark, Emma; Ross, Graham; Benyunes, Mark C.; Baselga, José

    2013-01-01

    Summary Background Primary results from the randomised, double-blind phase 3 study CLEOPATRA demonstrated significantly improved median progression-free survival (PFS) with pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer (MBC). Overall survival (OS) data at the primary analysis showed a strong trend in favour of the pertuzumab arm but did not reach statistical significance. Here we report confirmatory OS results after one additional year of follow-up. Methods Patients were randomly assigned to study treatment. OS and investigator-assessed PFS were analysed using the Kaplan-Meier approach and log-rank tests stratified by geographic region and prior treatment status. This trial is registered with ClinicalTrials.gov, NCT00567190. Findings In the intent-to-treat population (808 patients), 267 deaths had occurred at data cut-off (placebo arm: 154 of 406 [37·9%], pertuzumab arm: 113 of 402 [28·1%]). Treatment with pertuzumab plus trastuzumab plus docetaxel resulted in a 34% reduction in the risk of death during the course of the study (HR=0·66; 95% CI 0·52–0·84; p=0·0008). Median OS was 37·6 months in the placebo arm and was not yet reached in the pertuzumab arm. A descriptive follow-up analysis of investigator-assessed PFS showed a median PFS of 12·4 and 18·7 months in the placebo versus pertuzumab arm (HR=0·69; 95% CI 0·58–0·81). No new safety concerns were identified with one additional year of follow-up. Adverse events were similar to those reported at the primary analysis with respect to incidence, severity, and specificity. Interpretation This OS analysis demonstrated statistically significant and clinically meaningful survival benefit with pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive MBC. Updated analyses of investigator-assessed PFS and safety were consistent with the

  19. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    PubMed

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  20. Feasibility study of a randomised controlled trial to compare (deferred) androgen deprivation therapy and cryotherapy in men with localised radiation-recurrent prostate cancer

    PubMed Central

    Salji, M; Jones, R; Paul, J; Birrell, F; Dixon-Hughes, J; Hutchison, C; Johansen, T E B; Greene, D; Parr, N; Leung, H Y

    2014-01-01

    Background: Salvage therapeutic options for biochemical failure after primary radiation-based therapy include radical prostatectomy, cryoablation, high-intensity focused ultrasound (HIFU), brachytherapy (for post-EBRT patients) and androgen deprivation therapy (ADT). ADT and salvage prostate cryoablation (SPC) are two commonly considered treatment options for RRPC. However, there is an urgent need for high-quality clinical studies to support evidence-based decisions on treatment choice. Our study aims to determine the feasibility of randomising men with RRPC for treatment with ADT and SPC. Methods: The randomised controlled trial (CROP) was developed, which incorporated protocols to assess parameters relating to cryotherapy procedures and provide training workshops for optimising patient recruitment. Analysis of data from the recruitment phase and patient questionnaires was performed. Results: Over a period of 18 months, 39 patients were screened for eligibility. Overall 28 patients were offered entry into the trial, but only 7 agreed to randomisation. The majority reason for declining entry into the trial was an unwillingness to be randomised into the study. ‘Having the chance of getting cryotherapy' was the major reason for accepting the trial. Despite difficulty in retrieving cryotherapy temperature parameters from prior cases, 9 of 11 cryotherapy centres progressed through the Cryotherapists Qualification Process (CQP) and were approved for recruiting into the CROP study. Conclusions: Conveying equipoise between the two study arms for a salvage therapy was challenging. The use of delayed androgen therapy may have been seen as an inferior option. Future cohort studies into available salvage options (including prostate cryotherapy) for RRPC may be more acceptable to patients than randomisation within an RCT. PMID:24946001

  1. Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder—the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes): a randomised controlled single-blind trial

    PubMed Central

    Faurholt-Jepsen, Maria; Vinberg, Maj; Christensen, Ellen Margrethe; Frost, Mads; Bardram, Jakob; Kessing, Lars Vedel

    2013-01-01

    Introduction Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms. It has never been tested in a randomised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder. We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder. Methods We developed the MONARCA application for Android-based Smartphones, allowing patients suffering from bipolar disorder to do daily self-monitoring—including an interactive feedback loop between patients and clinicians through a web-based interface. The effect of the application was tested in a parallel-group, single-blind randomised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18–60 years who were given the use of a Smartphone with the MONARCA application (intervention group) or to the use of a cell phone without the application (placebo group) during a 6-month study period. The study was carried out from September 2011. The outcomes were changes in affective symptoms (primary), social functioning, perceived stress, self-rated depressive and manic symptoms, quality of life, adherence to medication, stress and cognitive functioning (secondary and tertiary). Analysis Recruitment is ongoing. Ethics Ethical permission has been obtained. Dissemination Positive, neutral and negative findings of the study will be published. Registration details The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark (H-2-2011-056) and The Danish Data Protection Agency (2013-41-1710). The trial is registered at ClinicalTrials.gov as NCT01446406. PMID:23883891

  2. Differences in long-term fixation between mobile-bearing and fixed-bearing knee prostheses at ten to 12 years' follow-up: a single-blinded randomised controlled radiostereometric trial.

    PubMed

    Pijls, B G; Valstar, E R; Kaptein, B L; Nelissen, R G H H

    2012-10-01

    This single-blinded randomised controlled trial investigated whether one design of mobile-bearing (MB) total knee replacement (TKR) has any advantage over a fixed-bearing (FB) design on long-term fixation as measured by radiostereometry. The amount of wear underneath the mobile bearing was also evaluated. A series of 42 knees was randomised to MB or FB tibial components with appropriate polyethylene inserts and followed for between ten and 12 years, or until the death of the patient. The polyethylene in the MB group was superior in that it was gamma-irradiated in inert gas and was calcium-stearate free; the polyethylene in the FB group was gamma-irradiated in air and contained calcium stearate. In theory this should be advantageous to the wear rate of the MB group. At final follow-up the overall mean migration was 0.75 mm (SD 0.76) in the MB group and 0.66 mm (SD 0.4) in the FB group, with the FB group demonstrating more posterior tilt and the MB group more internal rotation. In the FB group there was one revision for aseptic loosening, but none in the MB group. There were no significant differences in clinical or radiological scores. For the MB group, the mean linear wear rate on the under-surface was 0.026 mm/year (SD 0.014). This was significantly smaller than the wear rate of 0.11 mm/year (SD 0.06) in the MB between femur and polyethylene (p < 0.001). Nevertheless, even in a best-case setting the mobile bearings of this TKR design had no apparent advantage in terms of fixation over the FB knee prosthesis at ten to 12 years. The wear underneath the mobile bearing was small and is unlikely to be clinically relevant.

  3. A cluster-randomised, parallel group, controlled intervention study of genetic prostate cancer risk assessment and use of PSA tests in general practice—the ProCaRis study: study protocol

    PubMed Central

    Kirkegaard, Pia; Vedsted, Peter; Edwards, Adrian; Fenger-Grøn, Morten; Bro, Flemming

    2013-01-01

    Introduction Unsystematic screening for prostate cancer (PCa) is common, causing a high number of false-positive results. Valid instruments for assessment of individual risk of PCa have been called for. A DNA-based genetic test has been tested retrospectively. The clinical use of this test needs further investigation. The primary objective is to evaluate the impact on the use of prostate-specific antigen (PSA) tests of introducing genetic PCa risk assessment in general practice. The secondary objectives are to evaluate PCa-related patient experiences, and to explore sociocultural aspects of genetic risk assessment in patients at high PCa risk. Methods and analysis The study is a cluster-randomised, controlled intervention study with practice as the unit of randomisation. We expect 140 practices to accept participation and include a total of 1244 patients in 4 months. Patients requesting a PSA test in the intervention group practices will be offered a genetic PCa risk assessment. Patients requesting a PSA test in the control group practices will be handled according to current guidelines. Data will be collected from registers, patient questionnaires and interviews. Quantitative data will be analysed according to intention-to-treat principles. Baseline characteristics will be compared between groups. Longitudinal analyses will include time in risk, and multivariable analysis will be conducted to evaluate the influence of general practitioner and patient-specific variables on future PSA testing. Interview data will be transcribed verbatim and analysed from a social-constructivist perspective. Ethics and dissemination Consent will be obtained from patients who can withdraw from the study at any time. The study provides data to the ongoing conceptual and ethical discussions about genetic risk assessment and classification of low-risk and high-risk individuals. The intervention model might be applicable to other screening areas regarding risk of cancer with identified

  4. Acupuncture and PC6 stimulation for the prevention of postoperative nausea and vomiting in patients undergoing elective laparoscopic resection of colorectal cancer: a study protocol for a three-arm randomised pilot trial

    PubMed Central

    Kim, Kun Hyung; Kim, Dae Hun; Bae, Ji Min; Son, Gyung Mo; Kim, Kyung Hee; Hong, Seung Pyo; Yang, Gi Young; Kim, Hee Young

    2017-01-01

    Introduction This study aims to assess the feasibility of acupuncture and a Pericardium 6 (PC6) wristband as an add-on intervention of antiemetic medication for the prevention of postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic colorectal cancer resection. Methods and analysis A total of 60 participants who are scheduled to undergo elective laparoscopic resection of colorectal cancer will be recruited. An enhanced recovery after surgery protocol using standardised antiemetic medication will be provided for all participants. Participants will be equally randomised into acupuncture plus PC6 wristband (Acupuncture), PC6 wristband alone (Wristband), or no acupuncture or wristband (Control) groups using computer-generated random numbers concealed in opaque, sealed, sequentially numbered envelopes. For the acupuncture combined with PC6 wristband group, the embedded auricular acupuncture technique for preoperative anxiolysis and up to three sessions of acupuncture treatments with manual and electrical stimulation within 48 hours after surgery will be provided by qualified Korean medicine doctors. The PC6 wristband will be applied in the Acupuncture and Wristband groups, beginning 1 hour before surgery and lasting 48 hours postoperatively. The primary outcome will be the number of participants who experience moderate or severe nausea, defined as nausea at least 4 out of 10 on a severity numeric rating scale or vomiting at 24 hours after surgery. Secondary outcomes, including symptom severity, participant global assessments and satisfaction, quality of life, physiological recovery, use of medication and length of hospital stay, will be assessed. Adverse events and postoperative complications will be measured for 1 month after surgery. Ethics and dissemination All participants will provide written informed consent. The study has been approved by the institutional review board (IRB). This pilot trial will inform a full

  5. Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects.

    PubMed

    Zhang, Xiaoyan; Marjani, Sadie L; Hu, Zhaoyang; Weissman, Sherman M; Pan, Xinghua; Wu, Shixiu

    2016-03-15

    Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing.

  6. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    SciTech Connect

    Surinder Batra, Ph D

    2006-02-27

    its tumor: normal tissue ratio for improved therapeutic index, we engineered a variety antibody constructs. These constructs were evaluated using novel approaches like special radionuclides, pretargeting and optimization. Due to the smaller size, the engineered antibody molecules should penetrate better throughout a tumor mass, with less dose heterogeneity, than is the case with intact IgG. Multivalent scFvs with an appropriate radionuclide, therefore, hold promising prospects for cancer therapy and clinical imaging in MAb-based radiopharmaceuticals. In addition, the human anti-mouse antibodies (HAMA) responses in patients against antibody-based therapy are usually directed against the immunoglobulin constant regions; however, anti-idiotypic responses can also be detected. The HAMA responses reduce the efficacy of treatment by removing the circulating antibody molecules, fragments, and possibly scFvs by altering the pharmacokinetic properties of the antibody. HAMA responses against divalent IgG, divalent Ig fragments, and possibly multimeric scFvs could cause immune complex formation with hypersensitivity or allergic reactions that could be harmful to patients. The use of small molecules, such as scFvs (monomeric as well as multimeric), with their shorter biological half-lives and the lack of the constant regions and humanized variable (binding regions) performed in our studies should reduce the development of HAMA. The generation of humanized and fully human scFvs should further reduce the development of HAMA. Specific accomplishments on the project are the production of large amounts of recombinant antibodies as they are required in large amounts for cancer diagnosis and therapy. A variety of single-chain Fv (scFv) constructs were engineered for the desired pharmacokinetic properties. Tetrameric and dimeric scFvs showed a two-fold advantage: (1) there was a considerable gain in avidity as compared to smaller fragments, and (2) the biological half-life was more

  7. Single Walled Carbon Nanohorns as Photothermal Cancer Agents

    SciTech Connect

    Whitney, John; Sarkar, Saugata; Zhang, Jianfei; Do, Thao; Manson, Mary kyle; Campbell, Tom; Puretzky, Alexander A; Rouleau, Christopher M; More, Karren Leslie; Geohegan, David B; Rylander, Christopher; Dorn, Harry C; Rylander, Nichole M

    2011-01-01

    Nanoparticles have significant potential as selective photo-absorbing agents for laser based cancer treatment. This study investigates the use of single walled carbon nanohorns (SWNHs) as thermal enhancers when excited by near infrared (NIR) light for tumor cell destruction. Absorption spectra of SWNHs in deionized water at concentrations of 0, 0.01, 0.025, 0.05, 0.085, and 0.1 mg/ml were measured using a spectrophotometer for the wavelength range of 200-1,400 nm. Mass attenuation coefficients were calculated using spectrophotometer transmittance data. Cell culture media containing 0, 0.01, 0.085, and 0.333 mg/ml SWNHs was laser irradiated at 1,064 nm wavelength with an irradiance of 40 W/cm{sup 2} for 0-5 minutes. Temperature elevations of these solutions during laser irradiation were measured with a thermocouple 8 mm away from the incident laser beam. Cell viability of murine kidney cancer cells (RENCA) was measured 24 hours following laser treatment with the previously mentioned laser parameters alone or with SWNHs. Cell viability as a function of radial position was determined qualitatively using trypan blue staining and bright field microscopy for samples exposed to heating durations of 2 and 6 minutes alone or with 0.085 mg/ml SWNHs. A Beckman Coulter Vi-Cell instrument quantified cell viability of samples treated with varying SWNH concentration (0, 0.01, 0.085, and 0.333 mg/ml) and heating durations of 0-6 minutes. Spectrophotometer measurements indicated inclusion of SWNHs increased light absorption and attenuation across all wavelengths. Utilizing SWNHs with laser irradiation increased temperature elevation compared to laser heating alone. Greater absorption and higher temperature elevations were observed with increasing SWNH concentration. No inherent toxicity was observed with SWNH inclusion. A more rapid and substantial viability decline was observed over time in samples exposed to SWNHs with laser treatment compared with samples experiencing laser

  8. Effects of different early rehabilitation techniques on haemodynamic and metabolic parameters in sedated patients: protocol for a randomised, single-bind, cross-over trial

    PubMed Central

    Medrinal, Clément; Combret, Yann; Prieur, Guillaume; Robledo Quesada, Aurora; Bonnevie, Tristan; Gravier, Francis Edouard; Frenoy, Éric; Contal, Olivier; Lamia, Bouchra

    2017-01-01

    Introduction Early rehabilitation has become widespread practice for patients in intensive care; however, the prevalence of intensive care unit-acquired weakness remains high and the majority of physiotherapy is carried out in bed. Several inbed rehabilitation methods exist, but we hypothesise that techniques that provoke muscle contractions are more effective than passive techniques. Methods A randomised, controlled cross-over study will be carried out to evaluate and compare the effectiveness of early rehabilitation techniques on cardiac output (CO) in sedated patients in intensive care. 20 intubated and sedated patients will undergo 4 10 min rehabilitation sessions. 2 sessions will involve ‘passive’ techniques based on mobilisations and inbed cycle ergometry and 2 involving electrostimulation of the quadriceps muscle and Functional Electrical Stimulation-cycling (FES-cycling). The primary outcome is CO measured by Doppler ultrasound. The secondary outcomes are right ventricular function, pulmonary systolic arterial pressure, muscle oxygenation and minute ventilation during exercise. Results and conclusion Approval has been granted by our Institutional Review Board (Comité de Protection des Personnes Nord-Ouest 3). The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. Trial registration number NCT02920684. PMID:28255448

  9. Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival

    PubMed Central

    Wyss, Annah B.; Weissler, Mark C.; Avery, Christy L.; Herring, Amy H.; Bensen, Jeannette T.; Barnholtz-Sloan, Jill S.; Funkhouser, William K.

    2014-01-01

    Purpose Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment. Methods Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study. Results None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites. Conclusions Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment. PMID:24487794

  10. The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials

    PubMed Central

    2013-01-01

    Introduction mTOR and its downstream effectors the 4E-binding protein 1 (4EBP1) and the p70 ribosomal S6 kinases (S6K1 and S6K2) are frequently upregulated in breast cancer, and assumed to be driving forces in tumourigenesis, in close connection with oestrogen receptor (ER) networks. Here, we investigated these factors as clinical markers in five different cohorts of breast cancer patients. Methods The prognostic significance of 4EBP1, S6K1 and S6K2 mRNA expression was assessed with real-time PCR in 93 tumours from the treatment randomised Stockholm trials, encompassing postmenopausal patients enrolled between 1976 and 1990. Three publicly available breast cancer cohorts were used to confirm the results. Furthermore, the predictive values of 4EBP1 and p4EBP1_S65 protein expression for both prognosis and endocrine treatment benefit were assessed by immunohistochemical analysis of 912 node-negative breast cancers from the Stockholm trials. Results S6K2 and 4EBP1 mRNA expression levels showed significant correlation and were associated with a poor outcome in all cohorts investigated. 4EBP1 protein was confirmed as an independent prognostic factor, especially in progesterone receptor (PgR)-expressing cancers. 4EBP1 protein expression was also associated with a poor response to endocrine treatment in the ER/PgR positive group. Cross-talk to genomic as well as non-genomic ER/PgR signalling may be involved and the results further support a combination of ER and mTOR signalling targeted therapies. Conclusion This study suggests S6K2 and 4EBP1 as important factors for breast tumourigenesis, interplaying with hormone receptor signalling. We propose S6K2 and 4EBP1 as new potential clinical markers for prognosis and endocrine therapy response in breast cancer. PMID:24131622

  11. Single Cell Characterization of Prostate Cancer Circulating Tumor Cells

    DTIC Science & Technology

    2011-08-01

    single cell sequencing protocol for CTCs (Figure 3). So far, using their protocol we have done whole transcriptome amplification and mRNA seq on 6 single...perform additional single cell sequencing profiles. In our application we also hypothesized that there would be heterogeneity in gene expression

  12. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components

    PubMed Central

    Dougados, M.; Combe, B.; Cantagrel, A.; Goupille, P.; Olive, P.; Schattenkirchner, M.; Meusser, S; Paimela, L; Rau, R.; Zeidler, H.; Leirisalo-Repo, M.; Peldan, K.

    1999-01-01

    OBJECTIVES—To investigate the potential clinical benefit of a combination therapy.
METHODS—205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (⩽1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
RESULTS—The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
CONCLUSION—This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

 Keywords: rheumatoid arthritis; combination therapy; sulphasalazine; methotrexate PMID:10364900

  13. Acid-base effects of a bicarbonate-balanced priming fluid during cardiopulmonary bypass: comparison with Plasma-Lyte 148. A randomised single-blinded study.

    PubMed

    Morgan, T J; Power, G; Venkatesh, B; Jones, M A

    2008-11-01

    Fluid-induced metabolic acidosis can be harmful and can complicate cardiopulmonary bypass. In an attempt to prevent this disturbance, we designed a bicarbonate-based crystalloid circuit prime balanced on physico-chemical principles with a strong ion difference of 24 mEq/l and compared its acid-base effects with those of Plasma-Lyte 148, a multiple electrolyte replacement solution containing acetate plus gluconate totalling 50 mEq/l. Twenty patients with normal acid-base status undergoing elective cardiac surgery were randomised 1:1 to a 2 litre prime of either bicarbonate-balanced fluid or Plasma-Lyte 148. With the trial fluid, metabolic acid-base status was normal following bypass initiation (standard base excess 0.1 (1.3) mEq/l, mean, SD), whereas Plasma-Lyte 148 produced a slight metabolic acidosis (standard base excess -2.2 (2.1) mEq/l). Estimated group difference after baseline adjustment was 3.6 mEq/l (95% confidence interval 2.1 to 5.1 mEq/l, P=0.0001). By late bypass, mean standard base excess in both groups was normal (0.8 (2.2) mEq/l vs. -0.8 (1.3) mEq/l, P=0.5). Strong ion gap values were unaltered with the trial fluid, but with Plasma-Lyte 148 increased significantly on bypass initiation (15.2 (2.5) mEq/l vs. 2.5 (1.5) mEq/l, P < 0.0001), remaining elevated in late bypass (8.4 (3.4) mEq/l vs. 5.8 (2.4) mEq/l, P < 0.05). We conclude that a bicarbonate-based crystalloid with a strong ion difference of 24 mEq/l is balanced for cardiopulmonary bypass in patients with normal acid-base status, whereas Plasma-Lyte 148 triggers a surge of unmeasured anions, persisting throughout bypass. These are likely to be gluconate and/or acetate. Whether surges of exogenous anions during bypass can be harmful requires further study.

  14. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial

    PubMed Central

    Guddeti, Raviteja R; Prasad, Abhiram; Matsuzawa, Yasushi; Aoki, Tatsuo; Rihal, Charanjit; Holmes, David; Best, Patricia; Lennon, Ryan J; Lerman, Lilach O; Lerman, Amir

    2016-01-01

    Objectives Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow. Methods In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified. Results Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (−17 (−26, −10) vs 26 (−15, 134); p=0.02 and −17 (−38, 14) vs 107 (2, 446); p=0.007, respectively). Conclusions Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI. Trial registration number

  15. Comparison of oxygen uptake during cycle ergometry with and without functional electrical stimulation in patients with COPD: protocol for a randomised, single-blind, placebo-controlled, cross-over trial

    PubMed Central

    Medrinal, Clément; Prieur, Guillaume; Debeaumont, David; Robledo Quesada, Aurora; Combret, Yann; Quieffin, Jean; Contal, Olivier; Lamia, Bouchra

    2016-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) has systemic repercussions that can lead to peripheral muscle dysfunction. Muscle atrophy reduces aerobic capacity, greatly limiting activities of daily living and quality of life. Pulmonary rehabilitation is the gold standard treatment for these patients, however, patients may not be able to reach sufficient training intensities for benefits to occur. Technologies such as functional electrical stimulation (FES) are currently being adapted and tested to enhance exercise training. We hypothesise that FES coupled with cycling (FES-cycling) will improve maximal uptake of oxygen (VO2) and aerobic capacity more than endurance training with placebo stimulation. Methods A randomised, single-blind, placebo-controlled crossover trial will be carried out to evaluate the effects of FES-cycling on VO2 during endurance exercise on a cycle ergometer in patients with COPD. 25 patients with COPD will carry out two 30 min sessions at a constant load; one session with active and one with placebo FES. The primary outcome is oxygen uptake recorded with a metabolic measurement system. Secondary outcomes include ventilation equivalent for oxygen, ventilation equivalent for carbon dioxide, cardiac output, lactate values, perceived dyspnoea and perceived muscle fatigue. Results and conclusions Approval has been granted by our Institutional Review Board (Comité de Protection des Personnes Nord-Ouest 3). The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. Trial registration number NCT02594722. PMID:27110364

  16. A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

    PubMed

    Grénman, Seija; Wiklund, Tom; Jalkanen, Jyrki; Kuoppala, Tapio; Mäenpää, Johanna; Kuronen, Arja; Leminen, Arto; Puistola, Ulla; Vuolo-Merilä, Päivi; Salmi, Tuula; Vuento, Maarit; Yliskoski, Merja; Itälä, Maija; Helenius, Hans; Joensuu, Heikki; Lehtovirta, Pentti

    2006-09-01

    Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

  17. Influence of habitual dietary fibre intake on the responsiveness of the gut microbiota to a prebiotic: protocol for a randomised, double-blind, placebo-controlled, cross-over, single-centre study

    PubMed Central

    Healey, Genelle; Brough, Louise; Butts, Chrissie; Murphy, Rinki; Whelan, Kevin; Coad, Jane

    2016-01-01

    Introduction The commensal gut microbiota have been shown to have an impact on human health as aberrant gut microbiota have been linked to disease. Dietary constituents are influential in shaping the gut microbiota. Diet-specific therapeutic strategies may therefore play a role in optimising human health via beneficial manipulation of the gut microbiota. Research has suggested that an individual's baseline gut microbiota composition may influence how the gut microbiota respond to a dietary intervention and individuals with differing habitual dietary intakes appear to have distinct baseline gut microbiota compositions. The responsiveness of the gut microbiota may therefore be influenced by habitual dietary intakes. This study aims to investigate what influence differing habitual dietary fibre intakes have on the responsiveness of the gut microbiota to a prebiotic intervention. Methods and analysis In this randomised, double-blind, placebo-controlled, cross-over, single-centre study, 20 low dietary fibre (dietary fibre intake <18 g/day for females and <22 g/day for males) and 20 high dietary fibre (dietary fibre intake ≥25 g/day for females and ≥30 g/day for males) consumers will be recruited. Participants will be randomised to a placebo (Glucidex 29 Premium) or a prebiotic (Synergy 1) intervention for 3 weeks with a 3-week washout followed by 3 weeks of the alternative intervention. Outcome measures of gut microbiota composition (using 16S rRNA gene sequencing) and functional capacity (faecal short chain fatty acid concentrations and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) as well as appetite (visual analogue scale appetite questionnaire) will be assessed at the beginning and end of each intervention phase. Ethics and dissemination The Massey University Human Ethics Committee approved this study (Massey University HEC: Southern A application—15/34). Results will be disseminated through peer

  18. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

    PubMed Central

    Forbes, John F; Sestak, Ivana; Howell, Anthony; Bonanni, Bernardo; Bundred, Nigel; Levy, Christelle; von Minckwitz, Gunter; Eiermann, Wolfgang; Neven, Patrick; Stierer, Michael; Holcombe, Chris; Coleman, Robert E; Jones, Louise; Ellis, Ian; Cuzick, Jack

    2016-01-01

    Summary Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of

  19. African-American patients with cancer Talking About Clinical Trials (TACT) with oncologists during consultations: evaluating the efficacy of tailored health messages in a randomised controlled trial—the TACT study protocol

    PubMed Central

    Brown, R F; Davis, R; Wilson Genderson, M; Grant, S; Cadet, D; Lessard, M; Alpert, J; Ward, J; Ginder, G

    2016-01-01

    Introduction Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician–patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities. Objective (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct observation. (2) Demonstrate the efficacy of THM to improve patient outcomes associated with barriers to AA participation. (3) Explore associations among preconsultation levels of: (A) trust in medical researchers, (B) knowledge and attitudes towards CTs, (C) patient-family member congruence in decision-making, and (D) involvement/information preferences, and group assignment. Methods and analysis First, using established methods, we will develop THM materials. Second, the efficacy of the intervention is determined in a 2 by 2 factorial randomised controlled trial to test the effectiveness of (1) providing 357 AA patients with cancer with THM with 2 different ‘depths’ of tailoring and (2) either providing feedback to oncologists about the patients' trial THM or not. The primary analysis compares patient engaged communication in 4 groups preconsultation and postconsultation. Ethics and dissemination This study was approved by the Virginia Commonwealth University Institutional Review Board. To facilitate use of the THM intervention in diverse settings, we will convene ‘user groups’ at 3 major US cancer centres. To facilitate dissemination, we will post all materials and the implementation guide in publicly available locations. Trial registration number

  20. The Effectiveness of Group-based Self-management Programmes to Improve Physical and Psychological Outcomes in Patients with Cancer: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

    PubMed

    Smith-Turchyn, J; Morgan, A; Richardson, J

    2016-05-01

    The purpose of this study was to determine if patients with cancer who participate in group-based self-management programmes have better physical and psychological outcomes than patients with cancer who do not participate in group-based self-management programmes. A literature search was conducted in Ovid MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, Web of Science and ProQUEST using the terms 'self-management' OR 'self-care' AND 'cancer' OR 'neoplasm'. Randomised controlled trials comparing outcomes for people with cancer participating in group-based self-management programmes with those not participating in these programmes were selected after screening by two reviewers. Initial searches yielded 563 articles. Two reviewers independently extracted data using piloted forms and assessed risk of bias using Cochrane's tool. Standard mean differences were calculated for continuous outcomes. The percentage of variability due to heterogeneity was assessed using I(2). A subgroup analysis was carried out where possible. Six trials were included in the review after 141 full-text articles were screened. Group-based self-management programmes were found to improve physical function [standard mean difference (95% confidence interval) = 0.34 (0.02, 0.65), P = 0.04]. No significant results were found between groups for quality of life [0.48 (-0.16, 1.11), P = 0.14] and physical activity level [0.21 (-0.07, 0.5), P = 0.15] outcomes. Group-based self-management programmes for individuals with cancer resulted in improvements in physical outcomes. However, considerable heterogeneity was found between the included studies and the quality of evidence was very low for all main outcomes. Therefore the results should be viewed with caution.

  1. Single cell analysis of cancer cells using an improved RT-MLPA method has potential for cancer diagnosis and monitoring.

    PubMed

    Kvastad, L; Werne Solnestam, B; Johansson, E; Nygren, A O; Laddach, N; Sahlén, P; Vickovic, S; Bendigtsen, Schirmer C; Aaserud, M; Floer, L; Borgen, E; Schwind, C; Himmelreich, R; Latta, D; Lundeberg, J

    2015-11-12

    Single cell analysis techniques have great potential in the cancer genomics field. The detection and characterization of circulating tumour cells are important for identifying metastatic disease at an early stage and monitoring it. This protocol is based on transcript profiling using Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (RT-MLPA), which is a specific method for simultaneous detection of multiple mRNA transcripts. Because of the small amount of (circulating) tumour cells, a pre-amplification reaction is performed after reverse transcription to generate a sufficient number of target molecules for the MLPA reaction. We designed a highly sensitive method for detecting and quantifying a panel of seven genes whose expression patterns are associated with breast cancer, and optimized the method for single cell analysis. For detection we used a fluorescence-dependent semi-quantitative method involving hybridization of unique barcodes to an array. We evaluated the method using three human breast cancer cell lines and identified specific gene expression profiles for each line. Furthermore, we applied the method to single cells and confirmed the heterogeneity of a cell population. Successful gene detection from cancer cells in human blood from metastatic breast cancer patients supports the use of RT-MLPA as a diagnostic tool for cancer genomics.

  2. Laryngeal Cancer: 12-Year Experience of a Single Center.

    PubMed

    Calkovsky, V; Wallenfels, P; Calkovska, A; Hajtman, A

    2016-01-01

    Laryngeal cancer is about the twentieth most common cancer in the world and more than 150,000 new cases are diagnosed annually. The aim of the study was to evaluate the history, diagnostics, treatment outcomes, and prognosis in patients with laryngeal cancer in Northern Slovakia. We analyzed retrospectively 227 patients (207 males, 20 females) with laryngeal carcinoma treated in the period 2003-2014 at the Clinic of Otorhinolaryngology and Head and Neck Surgery of the Jessenius Faculty of Medicine and Martin University Hospital in Martin, Slovakia. The majority of patients were in the sixth (38.0 %) and seventh decade of life (30.8 %). Two hundred and seventeen patients (95.6 %) were smokers or ex-smokers. Sixty-six percent of patients were diagnosed with glottic or transglottic carcinoma, related probably to the anatomical structure of the larynx and exposure to inhalation pollutants. It is alarming that the majority of patients with malignant laryngeal disease were admitted to the hospital in advanced stages. In 151 (66.5 %) of patients, the extent of infiltration was T3 or T4, and 156 (68 %) patients were in disease stage III and IV. The incidence and mortality of laryngeal cancer suggest the need to intensify the prevention and to search for an early clinical stage of laryngeal cancer using a targeted screening.

  3. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients

    PubMed Central

    Ni, Xiaohui; Zhuo, Minglei; Su, Zhe; Duan, Jianchun; Gao, Yan; Wang, Zhijie; Zong, Chenghang; Bai, Hua; Chapman, Alec R.; Zhao, Jun; Xu, Liya; An, Tongtong; Ma, Qi; Wang, Yuyan; Wu, Meina; Sun, Yu; Wang, Shuhang; Li, Zhenxiang; Yang, Xiaodan; Yong, Jun; Su, Xiao-Dong; Lu, Youyong; Bai, Fan; Xie, X. Sunney; Wang, Jie

    2013-01-01

    Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics. PMID:24324171

  4. Single and Multiple Gene Manipulations in Mouse Models of Human Cancer

    PubMed Central

    Lehman, Heather L; Stairs, Douglas B

    2015-01-01

    Mouse models of human cancer play a critical role in understanding the molecular and cellular mechanisms of tumorigenesis. Advances continue to be made in modeling human disease in a mouse, though the relevance of a mouse model often relies on how closely it is able to mimic the histologic, molecular, and physiologic characteristics of the respective human cancer. A classic use of a genetically engineered mouse in studying cancer is through the overexpression or deletion of a gene. However, the manipulation of a single gene often falls short of mimicking all the characteristics of the carcinoma in humans; thus a multiple gene approach is needed. Here we review genetic mouse models of cancers and their abilities to recapitulate human carcinoma with single versus combinatorial approaches with genes commonly involved in cancer. PMID:26380553

  5. Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells

    PubMed Central

    Ramirez, Lisa; Herschkowitz, Jason I.; Wang, Jun

    2016-01-01

    Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don’t have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future. PMID:27581736

  6. Electrochemical detection of single cancer and healthy cell collisions on a microelectrode.

    PubMed

    Dick, Jeffrey E

    2016-09-18

    The electrochemical detection of single cancer cells and healthy cells is reported. Detection was achieved by monitoring the consumption of a single cell's contents upon its collisions with a microelectrode in the presence of surfactant. The electrochemical response between acute lymphoblastic lymphoma T-cells and healthy thymocytes differed by two orders of magnitude.

  7. Dead space closure with quilting suture versus conventional closure with drainage for the prevention of seroma after mastectomy for breast cancer (QUISERMAS): protocol for a multicentre randomised controlled trial

    PubMed Central

    Ouldamer, Lobna; Bonastre, Julia; Brunet-Houdard, Solène; Body, Gilles; Giraudeau, Bruno; Caille, Agnès

    2016-01-01

    Introduction Postoperative wound seroma is common after mastectomy. This complication is associated with significant impact on patient outcomes and healthcare costs. The optimal closure approach for seroma prevention remains unknown but some evidence suggests that quilting suture of the dead space could lower the incidence of seroma. The aim of this trial is to compare seroma formation using quilting suture versus conventional closure with drainage in patients undergoing mastectomy. Methods and analysis This is a multicentre, superiority, randomised controlled trial in women undergoing mastectomy with or without axillary involvement. Exclusion criteria include indication of bilateral mastectomy or immediate reconstruction and any physical or psychiatric condition that could impair patient's ability to cooperate with postoperative data collection or that do not allow an informed consent. 320 participants will be randomised in a 1:1 ratio to receive either quilting suture or conventional wound closure with drain. The primary outcome is seroma requiring either aspiration or surgical intervention within 21 days following mastectomy. Secondary outcomes include seroma regardless of whether or not it requires an intervention, surgical site infection, pain score, cosmetic result, patient's quality of life, costs and cost-effectiveness. The primary analysis will be an intention-to treat analysis performed with a χ2 test (or Fisher's exact test). Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS—Region Centre—Ouest 1, 2014-R20, 16 December 2014). Study findings will be published in peer-reviewed journals and presented at relevant national and international breast cancer conferences. Trial registration number NCT02263651. PMID:27044574

  8. Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    PubMed

    Uttley, Lesley; Whyte, Sophie; Gomersall, Timothy; Ren, Shijie; Wong, Ruth; Chambers, Duncan; Tappenden, Paul

    2016-12-10

    As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and cost effectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with luteinising hormone releasing-hormone (LHRH) agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice. Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution because of flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG's preferred base case, the deterministic incremental cost-effectiveness analysis (ICER) for degarelix versus 3-monthly triptorelin was £14,798 per quality-adjusted life-year (QALY) gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee's preferred assumptions suggested that degarelix was not cost effective for the subgroup with

  9. Single Cell Characterization of Prostate Cancer-Circulating Tumor Cells

    DTIC Science & Technology

    2013-09-01

    Ribonuclease Inhibitor (Life Technolo- gies)/0.2% Triton X-100 (10% solution, Sigma) prepared in nuclease free water . Collected cells were flash frozen on dry...CellSearch analysis. Clin Cancer Res 16: 5233–5243. 39. Weichert W, Schmidt M, Gekeler V, Denkert C, Stephan C, et al. (2004) Polo - like kinase 1 is

  10. Single-band upconversion nanoprobes for multiplexed simultaneous in situ molecular mapping of cancer biomarkers

    NASA Astrophysics Data System (ADS)

    Zhou, Lei; Wang, Rui; Yao, Chi; Li, Xiaomin; Wang, Chengli; Zhang, Xiaoyan; Xu, Congjian; Zeng, Aijun; Zhao, Dongyuan; Zhang, Fan

    2015-04-01

    The identification of potential diagnostic markers and target molecules among the plethora of tumour oncoproteins for cancer diagnosis requires facile technology that is capable of quantitatively analysing multiple biomarkers in tumour cells and tissues. Diagnostic and prognostic classifications of human tumours are currently based on the western blotting and single-colour immunohistochemical methods that are not suitable for multiplexed detection. Herein, we report a general and novel method to prepare single-band upconversion nanoparticles with different colours. The expression levels of three biomarkers in breast cancer cells were determined using single-band upconversion nanoparticles, western blotting and immunohistochemical technologies with excellent correlation. Significantly, the application of antibody-conjugated single-band upconversion nanoparticle molecular profiling technology can achieve the multiplexed simultaneous in situ biodetection of biomarkers in breast cancer cells and tissue specimens and produce more accurate results for the simultaneous quantification of proteins present at low levels compared with classical immunohistochemical technology.

  11. A randomised study comparing granulocyte-colony stimulating factor (G-CSF) with G-CSF plus thymostimulin in the treatment of haematological toxicity in patients with advanced breast cancer after high dose mitoxantrone therapy.

    PubMed

    Sanchiz, F; Milla, A

    1996-01-01

    54 patients with advanced breast cancer were randomised into a prospective, non-blinded, controlled trial to receive: mitoxantrone 28 mg/m2 intravenous day 1 and granulocyte-colony stimulating factor (G-CSF) 5 micrograms/kg/day subcutaneously days 2 to 16 (n = 27) or the same regimen plus thymostimulin (TS) 50 mg/day intramuscular at days 2 to 16 (n = 27). The median time to reach a neutrophil count greater than 0.5 x 10(9)/l was lower in the G-CSF+TS treated group (9.13 versus 3.24 days; P < 0.0005). More patients experienced neutropenic fever in the G-CSF group than in the G-CSF+TS group (59.3% versus 22.2%, P = 0.0119). The incidence, duration and severity of clinically or bacteriologically documented infection were lower in patients who received TS. 16 patients (59.3%) in the G-CSF group contracted infection, and 4 patients (14.8%) receiving G-CSF+TS (P = 0.0016). These data indicate that the combination of G-CSF and TS is well-tolerated and may enhance haematological recovery following myelosuppressive chemotherapy in patients with advanced breast cancer.

  12. Combined genome and transcriptome analysis of single disseminated cancer cells from bone marrow of prostate cancer patients reveals unexpected transcriptomes.

    PubMed

    Gužvić, Miodrag; Braun, Bernhard; Ganzer, Roman; Burger, Maximilian; Nerlich, Michael; Winkler, Sebastian; Werner-Klein, Melanie; Czyż, Zbigniew T; Polzer, Bernhard; Klein, Christoph A

    2014-12-15

    Bone is the most frequent site of metastasis in prostate cancer and patients with bone metastases are deemed incurable. Targeting prostate cancer cells that disseminated to the bone marrow before surgery and before metastatic outgrowth may therefore prevent lethal metastasis. This prompted us to directly analyze the transcriptome of disseminated cancer cells (DCC) isolated from patients with nonmetastatic (UICC stage M0) prostate cancer. We screened 105 bone marrow samples of patients with M0-stage prostate cancer and 18 bone marrow samples of patients without malignancy for the presence of EpCAM(+) single cells. In total, we isolated 270 cells from both groups by micromanipulation and globally amplified their mRNA. We used targeted transcriptional profiling to unambiguously identify DCCs for subsequent in-depth analysis. Transcriptomes of all cells were examined for the expression of EPCAM, KRT8, KRT18, KRT19, KRT14, KRT6a, KRT5, KLK3 (PSA), MAGEA2, MAGEA4, PTPRC (CD45), CD33, CD34, CD19, GYPC, SCL4A1 (band 3), and HBA2. Using these transcripts, we found it impossible to reliably identify true DCCs. We then applied combined genome and transcriptome analysis of single cells and found that EpCAM(+) cells from controls expressed transcripts thought to be epithelial-specific, whereas true DCCs may express hematopoietic transcripts. These results point to an unexpected transcriptome plasticity of epithelial cancer cells in bone marrow and question common transcriptional criteria to identify DCCs.

  13. Single nucleotide polymorphisms as susceptibility, prognostic, and therapeutic markers of nonsmall cell lung cancer

    PubMed Central

    Zienolddiny, Shanbeh; Skaug, Vidar

    2012-01-01

    Lung cancer is a major public health problem throughout the world. Among the most frequent cancer types (prostate, breast, colorectal, stomach, lung), lung cancer is the leading cause of cancer-related deaths worldwide. Among the two major subtypes of small cell lung cancer and nonsmall cell lung cancer (NSCLC), 85% of tumors belong to the NSCLC histological types. Small cell lung cancer is associated with the shortest survival time. Although tobacco smoking has been recognized as the major risk factor for lung cancer, there is a great interindividual and interethnic difference in risk of developing lung cancer given exposure to similar environmental and lifestyle factors. This may indicate that in addition to chemical and environmental factors, genetic variations in the genome may contribute to risk modification. A common type of genetic variation in the genome, known as single nucleotide polymorphism, has been found to be associated with susceptibility to lung cancer. Interestingly, many of these polymorphisms are found in the genes that regulate major pathways of carcinogen metabolism (cytochrome P450 genes), detoxification (glutathione S-transferases), adduct removal (DNA repair genes), cell growth/apoptosis (TP53/MDM2), the immune system (cytokines/chemokines), and membrane receptors (nicotinic acetylcholine and dopaminergic receptors). Some of these polymorphisms have been shown to alter the level of mRNA, and protein structure and function. In addition to being susceptibility markers, several of these polymorphisms are emerging to be important for response to chemotherapy/radiotherapy and survival of patients. Therefore, it is hypothesized that single nucleotide polymorphisms will be valuable genetic markers in individual-based prognosis and therapy in future. Here we will review some of the most important single nucleotide polymorphisms in the metabolic pathways that may modulate susceptibility, prognosis, and therapy in NSCLC. PMID:28210120

  14. Single Chain Antibodies as Estrogen Receptor Repressors in Breast Cancer

    DTIC Science & Technology

    2000-06-01

    induction of apoptosis. classical mechanism of ER action. Potential Roles of PI-9-The high level of PI-9 in CTLs and Acknowledgments-We are indebted to...proteinase inhibitor 9 (PI-9). Since space in this annual report is limited, I will focus largely upon the PI-9 system. Studying the mechanism by which...could provide a mechanism by which breast cancer cells evade immune attack. Recently, through the use of differential display technology, Dr. Hiroshi

  15. Colorectal cancer mortality 10 years after a single round of guaiac faecal occult blood test (gFOBT) screening: experiences from a Danish screening cohort

    PubMed Central

    Bjerrum, Andreas; Andersen, Ole; Fischer, Anders; Lindebjerg, Jan; Lynge, Elsebeth

    2016-01-01

    Background In Denmark, colorectal cancer (CRC) is the third most frequent cancer. Randomised trials have shown that guaiac faecal occult blood test (gFOBT) screening can reduce CRC mortality, but a recent large randomised study from Finland did not find any effect. A feasibility study was carried out in Denmark in 2005–2006 where residents aged 50–74 years in 2 Danish counties were invited once to participate in gFOBT screening. We used the unique Danish registers to assess the impact of gFOBT screening in this group on CRC incidence and mortality. Methods In this cohort study, we followed a group comprising 166 277 individuals invited to screening and a reference group comprising the remaining 1 240 348 Danes of the same age. We linked the Danish population and health service registers to obtain information about colonoscopies, polypectomies, incident CRC and cause of death. Results After a median follow-up time of 8.9 years, the CRC mortality was significantly lower in the screening group than in the reference group with an adjusted HR (aHR) of 0.92 (95% CI 0.86 to 0.99), while the aHR for all-cause mortality was 0.95 (95% CI 0.94 to 0.96). For screening participants, the aHR for CRC mortality and all-cause mortality was 0.72 (0.64 to 0.80) and 0.59 (0.57 to 0.60), respectively. Conclusions About 10 years after a single round of gFOBT screening, we found a significant 8% deficit in CRC mortality in the screening group compared with other Danes. We found almost the same deficit in all-cause mortality, and on this basis, it is not possible to conclude that one screening round had an effect on CRC mortality. Our study indicated that close monitoring of the outcome of CRC screening is warranted. PMID:28074150

  16. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial

    PubMed Central

    Fearon, K C H; von Meyenfeldt, M F; Moses, A G W; van Geenen, R; Roy, A; Gouma, D J; Giacosa, A; Van Gossum, A; Bauer, J; Barber, M D; Aaronson, N K; Voss, A C; Tisdale, M J

    2003-01-01

    Aim: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. Methods: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein ± 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. Results: At enrolment, patients’ mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (Δ weight E: −0.25 kg/month versus C: −0.37 kg/month; p = 0.74) and LBM (Δ LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. Conclusion: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were

  17. No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk.

    PubMed

    Stevens, Victoria L; Rodriguez, Carmen; Sun, Juzhong; Talbot, Jeffrey T; Thun, Michael J; Calle, Eugenia E

    2008-12-01

    One-carbon metabolism mediates the interconversion of folates for the synthesis of precursors used in DNA synthesis, repair, and methylation. Inadequate folate nutrition or compromised metabolism can disrupt these processes and facilitate carcinogenesis. In this study, we investigated associations of 39 candidate single nucleotide polymorphisms (SNP) in 9 one-carbon metabolism genes with risk of prostate cancer using 1,144 cases and 1,144 controls from the Cancer Prevention Study-II Nutrition Cohort. None of these SNPs were significantly associated with prostate cancer risk, either overall or in cases with advanced prostate cancer. Thus, our findings do not support the hypothesis that common genetic variation in one-carbon metabolism genes influences prostate cancer risk.

  18. Massive genomic rearrangement acquired in a single catastrophic event during cancer development.

    PubMed

    Stephens, Philip J; Greenman, Chris D; Fu, Beiyuan; Yang, Fengtang; Bignell, Graham R; Mudie, Laura J; Pleasance, Erin D; Lau, King Wai; Beare, David; Stebbings, Lucy A; McLaren, Stuart; Lin, Meng-Lay; McBride, David J; Varela, Ignacio; Nik-Zainal, Serena; Leroy, Catherine; Jia, Mingming; Menzies, Andrew; Butler, Adam P; Teague, Jon W; Quail, Michael A; Burton, John; Swerdlow, Harold; Carter, Nigel P; Morsberger, Laura A; Iacobuzio-Donahue, Christine; Follows, George A; Green, Anthony R; Flanagan, Adrienne M; Stratton, Michael R; Futreal, P Andrew; Campbell, Peter J

    2011-01-07

    Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.

  19. A pilot randomised controlled trial of personalised care after treatment for prostate cancer (TOPCAT-P): nurse-led holistic-needs assessment and individualised psychoeducational intervention: study protocol

    PubMed Central

    Stanciu, Marian Andrei; Morris, Caroline; Makin, Matt; Watson, Eila; Bulger, Jenna; Evans, Richard; Hiscock, Julia; Hoare, Zoë; Edwards, Rhiannon Tudor; Neal, Richard David; Wilkinson, Clare

    2015-01-01

    Introduction Prostate cancer is common and the incidence is increasing, but more men are living longer after diagnosis, and die with their disease rather than of it. Nonetheless, specific and substantial physical, sexual, emotional and mental health problems often lead to a poor quality of life. Urology services increasingly struggle to cope with the demands of follow-up care, and primary care is likely to play the central role in long-term follow-up. The present phase II trial will evaluate the feasibility and acceptability of a nurse-led, person-centred psychoeducational intervention, delivered in community or primary care settings. Methods and analysis Prostate cancer survivors diagnosed in the past 9–48 months and currently biochemically stable will be identified from hospital records by their treating clinician. Eligible men would have either completed radical treatment, or would be followed up with prostate specific antigen monitoring and symptom reporting. We will recruit 120 patients who will be randomised to receive either an augmented form of usual care, or an additional nurse-led intervention for a period of 36 weeks. Following the health policy in Wales, the intervention is offered by a key worker, is promoting prudent healthcare and is using a holistic needs assessment. Outcome measures will assess physical symptoms, psychological well-being, confidence in managing own health and quality of life. Healthcare service use will be measured over 36 weeks. Feedback interviews with patients and clinicians will further inform the acceptability of the intervention. Recruitment, attrition, questionnaire completion rates and outcome measures variability will be assessed, and results will inform the design of a future phase III trial and accompanying economic evaluation. Ethics and dissemination Ethics approval was granted by Bangor University and North Wales REC (13/WA/0291). Results will be reported in peer-reviewed publications, at scientific

  20. Single-cell resolution diagnosis of cancer cells by carbon nanotube electrical spectroscopy

    NASA Astrophysics Data System (ADS)

    Abdolahad, M.; Janmaleki, M.; Taghinejad, M.; Taghnejad, H.; Salehi, F.; Mohajerzadeh, S.

    2013-03-01

    We report the use of vertically aligned carbon nanotubes (VACNTs) as electrical endoscopes (biosensors) for cancer metastatic diagnosis at single-cell resolution. The device is based on direct signal extraction by means of vertically aligned conductive carbon nanotubes from a live cell membrane, which has been disrupted during carcinogenesis at its primary and progressive stages. The value of this electrical disruption depends on the cancer metastatic grade. In addition, the electrical resonance behavior of the cell, halted during cancer progression, could be monitored as a new cancer diagnostic profile. By taking a second derivative of the cell impedance with respect to applied frequency, we have arrived at a new spectroscopy tool for distinguishing cancerous stages of colon and breast carcinoma cells.We report the use of vertically aligned carbon nanotubes (VACNTs) as electrical endoscopes (biosensors) for cancer metastatic diagnosis at single-cell resolution. The device is based on direct signal extraction by means of vertically aligned conductive carbon nanotubes from a live cell membrane, which has been disrupted during carcinogenesis at its primary and progressive stages. The value of this electrical disruption depends on the cancer metastatic grade. In addition, the electrical resonance behavior of the cell, halted during cancer progression, could be monitored as a new cancer diagnostic profile. By taking a second derivative of the cell impedance with respect to applied frequency, we have arrived at a new spectroscopy tool for distinguishing cancerous stages of colon and breast carcinoma cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr33430a

  1. Implications of single nucleotide polymorphisms in CD44 exon 2 for risk of breast cancer.

    PubMed

    Zhou, Juhua; Nagarkatti, Prakash S; Zhong, Yin; Zhang, Jiajia; Nagarkatti, Mitzi

    2011-09-01

    CD44 is a cell-surface glycoprotein involved in many cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis and tumor metastasis, suggesting that CD44 may play an important role in breast cancer development. In this study, we examined whether CD44 exon 2 polymorphisms are associated with increased susceptibility to breast cancer. Direct nucleotide sequencing analysis showed that multiple single nucleotide polymorphisms were present in the CD44 exon 2 coding region in female patients with breast cancer. There was no significant difference in the frequency of any one single nucleotide polymorphism in the CD44 exon 2 coding region between patients with breast cancer and normal donors. However, CD44 polymorphisms in the CD44 exon 2 coding region were identified in approximately 40% of patients with breast cancer, which was significantly higher than in normal donors (odds ratio, 9.34; 95% confidence interval = 2.58-33.82; P < 0.0001). The Wilcoxon-Mann-Whitney test analysis showed that the patients with the CD44 polymorphisms in CD44 exon 2 coding sequence had breast cancer at earlier ages, 49 ± 3 versus 62 ± 2 years (P < 0.0005), and larger tumor burdens (4.9 ± 1.22 vs. 1.6 ± 0.15 mm, P < 0.01) at the time of diagnosis. Interestingly, African-American female patients having the CD44 polymorphisms in CD44 exon 2 coding sequence were diagnosed with breast cancer at very young age (41 ± 2 years). Our results show that CD44 exon 2 polymorphisms are associated with breast cancer development, and such analysis may be effectively used in the evaluation of risk, prediction of cancer, prevention, diagnosis, and epidemiological studies of breast cancer.

  2. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  3. Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways

    PubMed Central

    Coleman, Ilsa; Lakely, Bryce; Coleman, Roger; Larson, Sandy; Aguirre-Ghiso, Julio A.; Xia, Jing; Gulati, Roman; Nelson, Peter S.; Montgomery, Bruce; Lange, Paul; Snyder, Linda A.; Vessella, Robert L.; Morrissey, Colm

    2014-01-01

    Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa), breast cancer, esophageal cancer, and other cancers. PCa disseminated tumor cells (DTC) are detected in both patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. We performed a first-in-field study of single DTC transcriptomic analyses in cancer patients to identify a molecular signature associated with cancer dormancy. We profiled eighty-five individual EpCAM+/CD45− cells from the bone marrow of PCa patients with NED or ADV. We analyzed 44 DTC with high prostate-epithelial signatures, and eliminated 41 cells with high erythroid signatures and low prostate epithelial signatures. DTC were clustered into 3 groups: NED, ADV_1, and ADV_2, in which the ADV_1 group presented a distinct gene expression pattern associated with the p38 stress activated kinase pathway. Additionally, DTC from the NED group were enriched for a tumor dormancy signature associated with head and neck squamous carcinoma and breast cancer. This study provides the first clinical evidence of the p38 pathway as a potential biomarker for early recurrence and an attractive target for therapeutic intervention. PMID:25301725

  4. Single-dose fentanyl sublingual spray for breakthrough cancer pain.

    PubMed

    Taylor, Donald R

    2013-01-01

    Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60-90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.

  5. Imaging in breast cancer: Single-photon computed tomography and positron-emission tomography

    PubMed Central

    Bénard, François; Turcotte, Éric

    2005-01-01

    Although mammography remains a key imaging method for the early detection and screening of breast cancer, the overall accuracy of this test remains low. Several radiopharmaceuticals have been proposed as adjunct imaging methods to characterize breast masses by single-photon-emission computed tomography (SPECT) and positron-emission tomography (PET). Useful in characterizing indeterminate palpable masses and in the detection of axillary metastases, these techniques are insufficiently sensitive to detect subcentimetric tumor deposits. Their role in staging nodal involvement of the axillary areas therefore currently remains limited. Several enzymes and receptors have been targeted for imaging breast cancers with PET. [18F]Fluorodeoxyglucose is particularly useful in the detection and staging of recurrent breast cancer and in assessing the response to chemotherapy. Several other ligands targeting proliferative activity, protein synthesis, and hormone and cell-membrane receptors may complement this approach by providing unique information about biological characteristics of breast cancer across primary and metastatic tumor sites. PMID:15987467

  6. Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

    PubMed Central

    Thorn, Joanna C; Turner, Emma L; Hounsome, Luke; Walsh, Eleanor; Down, Liz; Verne, Julia; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M; Noble, Sian M

    2016-01-01

    Objectives To evaluate the accuracy of routine data for costing inpatient resource use in a large clinical trial and to investigate costing methodologies. Design Final-year inpatient cost profiles were derived using (1) data extracted from medical records mapped to the National Health Service (NHS) reference costs via service codes and (2) Hospital Episode Statistics (HES) data using NHS reference costs. Trust finance departments were consulted to obtain costs for comparison purposes. Setting 7 UK secondary care centres. Population A subsample of 292 men identified as having died at least a year after being diagnosed with prostate cancer in Cluster randomised triAl of PSA testing for Prostate cancer (CAP), a long-running trial to evaluate the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Results Both inpatient cost profiles showed a rise in costs in the months leading up to death, and were broadly similar. The difference in mean inpatient costs was £899, with HES data yielding ∼8% lower costs than medical record data (differences compatible with chance, p=0.3). Events were missing from both data sets. 11 men (3.8%) had events identified in HES that were all missing from medical record review, while 7 men (2.4%) had events identified in medical record review that were all missing from HES. The response from finance departments to requests for cost data was poor: only 3 of 7 departments returned adequate data sets within 6 months. Conclusions Using HES routine data coupled with NHS reference costs resulted in mean annual inpatient costs that were very similar to those derived via medical record review; therefore, routinely available data can be used as the primary method of costing resource use in large clinical trials. Neither HES nor medical record review represent gold standards of data collection. Requesting cost data from finance departments is impractical for large clinical trials. Trial registration number ISRCTN92187251

  7. Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer.

    PubMed

    Gao, Bo; Russell, Amanda; Beesley, Jonathan; Chen, Xiao Qing; Healey, Sue; Henderson, Michelle; Wong, Mark; Emmanuel, Catherine; Galletta, Laura; Johnatty, Sharon E; Bowtell, David; Haber, Michelle; Norris, Murray; Harnett, Paul; Chenevix-Trench, Georgia; Balleine, Rosemary L; deFazio, Anna

    2014-05-09

    ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.

  8. The application of clinical variables and models to predict pulmonary embolism in cancer patients: a comprehensive single cancer center experience

    PubMed Central

    Mansour, Asem; Ismael, Yousef; Abunasser, Mahmoud; Hammode, Emad; Turfa, Rim; Abdel-Razeq, Hikmat

    2013-01-01

    Introduction Prompt diagnosis and treatment of pulmonary embolism (PE) can help reduce its associated morbidity and mortality. Computed tomography chest angiography (CTA) scanning is the most widely used diagnostic modality. In noncancer patients, only 10% of such studies are positive for PE. Clinical variables, individual or in combination, that can predict test positivity are highly needed. Materials and methods All CTAs requested to confirm or exclude a diagnosis of PE in a single comprehensive cancer center were reviewed. In addition to the Wells score, other clinical variables known to increase the risk of PE were analyzed. Results A total of 778 adult cancer patients were treated at King Hussein Cancer Center (Amman, Jordan) and were included in this study; the majority of patients (64.2%) had stage 4 disease. Overall, 129 (16.6%) patients had positive scans for PE, while alternative diagnoses were made in 308 (39.6%) patients. Cancer stage and anticancer treatment had no impact on positive PE rates. However, Wells criteria classified patients into three risk groups with PE rates of 10.2%, 16.1%, and 62.5% among the patients with low, moderate, and high risk, respectively (P < 0.0001). Duration of cancer diagnosis (<12 months versus >12 months) had a significant impact on positive PE studies (22.0% versus 12.4%, respectively, P = 0.007). Conclusion The rate of positive PE studies in cancer patients is higher than previously reported in noncancer patients. Positivity for PE was higher during the first 12 months of cancer diagnosis and in those with high probability score according to the Wells criteria. Factors like primary tumor stage and anticancer therapy had no significant impact on PE-positive studies. PMID:24187488

  9. The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393

    PubMed Central

    2005-01-01

    Background There have been concerns that low blood cholesterol concentrations may cause non-vascular mortality and morbidity. Randomisation of large numbers of people to receive a large, and prolonged, reduction in cholesterol concentrations provides an opportunity to address such concerns reliably. Methods 20,536 UK adults (aged 40–80 years) with vascular disease or diabetes were randomly allocated to receive 40 mg simvastatin daily or matching placebo. Prespecified safety analyses were of cause-specific mortality, and of total and site-specific cancer incidence. Comparisons between all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat") involved an average difference in blood total cholesterol concentration of 1.2 mmol/L (46 mg/dL) during the scheduled 5-year treatment period. Results There was a highly significant 17% (95% CI 9–25) proportional reduction in vascular deaths, along with a non-significant reduction in all non-vascular deaths, which translated into a significant reduction in all-cause mortality (p = 0.0003). The proportional reduction in the vascular mortality rate was about one-sixth in each subcategory of participant studied, including: men and women; under and over 70 years at entry; and total cholesterol below 5.0 mmol/L or LDL cholesterol below 3.0 mmol/L. No significant excess of non-vascular mortality was observed in any subcategory of participant (including the elderly and those with pretreatment total cholesterol below 5.0 mmol/L), and there was no significant excess in any particular cause of non-vascular mortality. Cancer incidence rates were similar in the two groups, both overall and in particular subcategories of participant, as well as at particular primary sites. There was no suggestion that any adverse trends in non-vascular mortality or morbidity were beginning to emerge with more prolonged treatment. Conclusion These findings, which are based on large numbers of deaths and non

  10. Randomised trial comparing combinations of cyclophosphamide and cisplatin without or with doxorubicin or 4'-epi-doxorubicin in the treatment of advanced ovarian cancer.

    PubMed

    Hernádi, Z; Juhász, B; Póka, R; Lampé, L G

    1988-10-01

    Forty-eight patients with FIGO stage III and IV epithelial carcinomas of the ovary were entered in this randomised trial. Radical surgery was performed and no residual tumor with a diameter greater than 2 cm was left behind. Of these patients 62.5% (10/16) had a complete or partial response on cyclophosphamide + cisplatin (CP) 87.5% (14/16) on cyclophosphamide + doxorubicin + cisplatin (CAP) and cyclophosphamide + 4'-epi-doxorubicin + cisplatin (CEP). The median time to progression was 3.5 months on CP, 12.5 months on CAP and 11.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer progression-free survival (log rank chi 2 = 5.4; P = 0.04). No significant difference was found, however, between patients on CAP and CEP. The median survival times were 12.5 months on CP, 26.5 months on CAP and 14.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer survival (logrank chi 2 = 9.08; P = 0.0099). No significant difference was found, however, between patients on CAP and CEP in terms of survival. Asymptomatic mild-to-moderate laboratory test toxicity occurred in 6-12% of patients on CP, 6-12% on CAP and no toxicity of this type and grade on CEP. Nausea and vomiting were also less severe and less frequent in the CEP group. Cardiotoxicity was seen in 12.5% (2/16) only in the CAP group.

  11. RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies

    PubMed Central

    Dahlberg, K; Odencrants, S; Hagberg, L

    2016-01-01

    Introduction Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. Methods and analysis This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery. The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A–C) at 1 and 2 weeks and (D) at 1 and 4 months. Trial registration number NCT02492191; Pre

  12. A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian Cancer Survival.

    PubMed

    Belotte, Jimmy; Fletcher, Nicole M; Saed, Mohammed G; Abusamaan, Mohammed S; Dyson, Gregory; Diamond, Michael P; Saed, Ghassan M

    2015-01-01

    Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2 negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR) of 3.68 (95% confidence interval (CI): 1.149-11.836)) for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, p<0.05) for those without the catalase SNP as compared to those with the SNP. Additionally, age at diagnosis greater than the median was found to be a significant predictor of death (HR of 2.78 (95% CI: 1.022-7.578)). This study indicates a strong association with the catalase SNP and survival of ovarian cancer patients, and thus may serve as a prognosticator.

  13. Differentiating cancerous tissues from noncancerous tissues using single-fiber reflectance spectroscopy with different fiber diameters

    NASA Astrophysics Data System (ADS)

    Sircan-Kuçuksayan, Aslinur; Denkceken, Tuba; Canpolat, Murat

    2015-11-01

    Elastic light-scattering spectra acquired with single-fiber optical probes with diameters of 100, 200, 400, 600, 800, 1000, 1200, and 1500 μm were used to differentiate cancerous from noncancerous prostate tissues. The spectra were acquired ex vivo on 24 excised prostate tissue samples collected from four patients. For each probe, the spectra and histopathology results were compared in order to investigate the correlation between the core diameters of the single-fiber optical probe and successful differentiation between cancerous and noncancerous prostate tissues. The spectra acquired using probes with a fiber core diameter of 400 μm or smaller successfully differentiated cancerous from noncancerous prostate tissues. Next, the spectra were acquired from monosized polystyrene microspheres with a diameter of 5.00±0.01 μm to investigate the correlation between the core diameters of the probes and the Mie oscillations on the spectra. Monte Carlo simulations of the light distribution of the tissue phantoms were run to interrogate whether the light detected by the probes with different fiber core diameters was in the ballistic or diffusive regime. If the single-fiber optical probes detect light in the ballistic regime, the spectra can be used to differentiate between cancerous and noncancerous tissues.

  14. The butterfly effect in cancer: a single base mutation can remodel the cell.

    PubMed

    Hart, Jonathan R; Zhang, Yaoyang; Liao, Lujian; Ueno, Lynn; Du, Lisa; Jonkers, Marloes; Yates, John R; Vogt, Peter K

    2015-01-27

    We have compared the proteome, transcriptome, and metabolome of two cell lines: the human breast epithelial line MCF-10A and its mutant descendant MCF-10A-H1047R. These cell lines are derived from the same parental stock and differ by a single amino acid substitution (H1047R) caused by a single nucleotide change in one allele of the PIK3CA gene, which encodes the catalytic subunit p110α of PI3K (phosphatidylinositol 3-kinase). They are considered isogenic. The H1047R mutation of PIK3CA is one of the most frequently encountered somatic cancer-specific mutations. In MCF-10A, this mutation induces an extensive cellular reorganization that far exceeds the known signaling activities of PI3K. The changes are highly diverse, with examples in structural protein levels, the DNA repair machinery, and sterol synthesis. Gene set enrichment analysis reveals a highly significant concordance of the genes differentially expressed in MCF-10A-H1047R cells and the established protein and RNA signatures of basal breast cancer. No such concordance was found with the specific gene signatures of other histological types of breast cancer. Our data document the power of a single base mutation, inducing an extensive remodeling of the cell toward the phenotype of a specific cancer.

  15. Can a single model explain both breast cancer and prostate cancer?

    PubMed Central

    Friedman, A Edward

    2007-01-01

    Background The Estradiol-Dihydrotestosterone model of prostate cancer (PC) showed how the interaction of hormones with specific hormone receptors affected apoptosis. The same hormone can produce different effects, depending on which hormone receptor it interacts with. Model This model proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol (E2). A sufficiently high enough local level of E2 results in telomerase activity. The telomerase activity allows cell division and may lead to BC or PC, which will proliferate if the rate of cell division is greater than the rate of cell death. The effect of hormones on their hormone receptors will affect the rate of cell death and determine whether or not the cancer proliferates. Conclusion By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments. PMID:17678531

  16. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials

    PubMed Central

    Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

    2011-01-01

    Summary Background As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. Methods We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21 457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. Findings In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0–4 and RR 0·68 [0·06] during years 5–9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10–14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10–19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0–4, 0·66 [0·05] during years 5–9, and 0·68 [0·08] during years 10–14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. Interpretation 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the

  17. An ex vivo, assessor blind, randomised, parallel group, comparative efficacy trial of the ovicidal activity of three pediculicides after a single application - melaleuca oil and lavender oil, eucalyptus oil and lemon tea tree oil, and a "suffocation" pediculicide

    PubMed Central

    2011-01-01

    Background There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length. Method Subjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). Treatment: The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. Results 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the

  18. rs621554 single nucleotide polymorphism of DLC1 is associated with breast cancer susceptibility and prognosis.

    PubMed

    Ding, Xia; Gao, Sumei; Yang, Qifeng

    2016-05-01

    Deleted in liver cancer 1 (DLC1) on chromosome 8p22, is an important tumor suppressor gene originally identified to be deleted in hepatocellular carcinoma. It can regulate the structure of the actin cytoskeleton and inhibit cell proliferation, motility and angiogenesis, which predominantly depends on its homology to rat RhoGAP. There are many genetic variants in DLC1, which may influence its antitumor efficacy. The rs621554 (IVS19+108C>T) polymorphism is a synonymous single nucleotide polymorphism (SNP) previously found to be associated with hepatocellular carcinoma. In the present study, 453 patients with breast cancer and 330 healthy females were analyzed using a cycling probe method. It was determined that the rs621554 polymorphism of DLC1 was associated with breast cancer susceptibility, with the CC and CT genotypes resulting in a higher risk of developing breast cancer. In regard to clinicopathological variables, it was demonstrated that the CT and CC genotype were associated with tumor size, lymph node metastasis and progesterone receptor status. Patients with the CT and CC genotype had shorter disease-free survival and overall survival rates compared with those with the TT genotype. Additionally, it was demonstrated that the rs621554 polymorphism was correlated with DLC1 expression at the mRNA level. These results suggested that the rs621554 polymorphism is associated with breast cancer susceptibility and prognosis, and may serve as a biomarker for breast cancer development and progression.

  19. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/− cetuximab in oesophageal cancer

    PubMed Central

    Crosby, T; Hurt, C N; Falk, S; Gollins, S; Staffurth, J; Ray, R; Bridgewater, J A; Geh, J I; Cunningham, D; Blazeby, J; Roy, R; Maughan, T; Griffiths, G; Mukherjee, S

    2017-01-01

    Background: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. Methods: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m−2 (day 1) and capecitabine 625 mg m−2 bd (days 1–21) for four cycles +/− cetuximab 400 mg m−2 day 1 then by 250 mg m−2 weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility. Results: About 258 patients (dCRT=129; dCRT+cetuximab (dCRT+C)=129) were recruited from 36 centres. About 72.9% (n=188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9–48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7–42.3) in dCRT and 24.7 (18.6–31.3) in dCRT+C (hazard ratio (HR)=1.25, 95% CIs: 0.93–1.69, P=0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3–29.9) and 15.9 (10.7–20.8) months, respectively (HR=1.28, 95% CIs: 0.94–1.75; P=0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS. Conclusions: The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy. PMID:28196063

  20. Circulating Immune Complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial

    PubMed Central

    Khanna, Sunali S; Karjodkar, Freny R

    2006-01-01

    Aim To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. Methods Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. Results The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. Conclusion The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment. PMID:17040577

  1. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

    PubMed Central

    Wasan, Harpreet; Meade, Angela M; Adams, Richard; Wilson, Richard; Pugh, Cheryl; Fisher, David; Sydes, Benjamin; Madi, Ayman; Sizer, Bruce; Lowdell, Charles; Middleton, Gary; Butler, Rachel; Kaplan, Richard; Maughan, Tim

    2014-01-01

    Summary Background Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy. Methods COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681. Findings We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those

  2. Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.

    PubMed

    Eirew, Peter; Steif, Adi; Khattra, Jaswinder; Ha, Gavin; Yap, Damian; Farahani, Hossein; Gelmon, Karen; Chia, Stephen; Mar, Colin; Wan, Adrian; Laks, Emma; Biele, Justina; Shumansky, Karey; Rosner, Jamie; McPherson, Andrew; Nielsen, Cydney; Roth, Andrew J L; Lefebvre, Calvin; Bashashati, Ali; de Souza, Camila; Siu, Celia; Aniba, Radhouane; Brimhall, Jazmine; Oloumi, Arusha; Osako, Tomo; Bruna, Alejandra; Sandoval, Jose L; Algara, Teresa; Greenwood, Wendy; Leung, Kaston; Cheng, Hongwei; Xue, Hui; Wang, Yuzhuo; Lin, Dong; Mungall, Andrew J; Moore, Richard; Zhao, Yongjun; Lorette, Julie; Nguyen, Long; Huntsman, David; Eaves, Connie J; Hansen, Carl; Marra, Marco A; Caldas, Carlos; Shah, Sohrab P; Aparicio, Samuel

    2015-02-19

    Human cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.

  3. Laparoendoscopic single-site radical hysterectomy for early stage cervical cancer

    PubMed Central

    Park, Ju Young; Kim, Yoo Min; Lee, Yoo-Young; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2017-01-01

    Technical developments have made laparoendoscopic single-site (LESS) surgery increasingly more feasible for treating gynecological conditions, including cancer. However, complex surgeries such as radical hysterectomy have rarely been performed with single-port access because of technical difficulties. The majority of the difficulties are due to the inefficient retraction of tissue during dissection. Here, we report a detailed description of LESS radical hysterectomy plus pelvic lymph node dissection that was successfully performed in two patients with stage IB1 cervical cancer. We used our expertise with LESS to perform space development as much as possible before the ligaments were resected. The oncologic clearance was comparable to that of conventional laparoscopic radical hysterectomy. PMID:28217681

  4. Single-site robotic surgery in gynecologic cancer: a pilot study

    PubMed Central

    Yoo, Ha-Na; Lee, Yoo-Young; Choi, Chel Hun; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2015-01-01

    Objective To discuss the feasibility of single-site robotic surgery for benign gynecologic tumors and early stage gynecologic cancers. Methods In this single institution, prospective analysis, we analyzed six patients who had undergone single-site robotic surgery between December 2013 and August 2014. Surgery was performed using the da Vinci Si Surgical System. Patient characteristics and surgical outcomes were analyzed. Results Single-site robotic surgery was performed successfully in all six cases. The median patient age was 48 years, and the median body mass index was 25.5 kg/m2 (range, 22 to 33 kg/m2). The median total operative time was 211 minutes, and the median duration of intracorporeal vaginal cuff suturing was 32 minutes (range, 22 to 47 minutes). The median duration of pelvic lymph node dissection was 31 minutes on one side and 27 minutes on the other side. Patients' postoperative courses were uneventful. The median postoperative hospital stay was 4 days. No postoperative complications occurred. Conclusion When used to treat benign gynecologic tumors and early stage gynecologic cancers, the single-site da Vinci robotic surgery is feasible, safe, and produces favorable surgical outcomes. PMID:25609162

  5. Eating As Treatment (EAT) study protocol: a stepped-wedge, randomised controlled trial of a health behaviour change intervention provided by dietitians to improve nutrition in patients with head and neck cancer undergoing radiotherapy

    PubMed Central

    Britton, Ben; McCarter, Kristen; Baker, Amanda; Wolfenden, Luke; Wratten, Chris; Bauer, Judith; Beck, Alison; McElduff, Patrick; Halpin, Sean; Carter, Gregory

    2015-01-01

    Introduction Maintaining adequate nutrition for Head and Neck Cancer (HNC) patients is challenging due to both the malignancy and the rigours of radiation treatment. As yet, health behaviour interventions designed to maintain or improve nutrition in patients with HNC have not been evaluated. The proposed trial builds on promising pilot data, and evaluates the effectiveness of a dietitian-delivered health behaviour intervention to reduce malnutrition in patients with HNC undergoing radiotherapy: Eating As Treatment (EAT). Methods and analysis A stepped-wedge cluster randomised design will be used. All recruitment hospitals begin in the control condition providing treatment as usual. In a randomly generated order, oncology staff at each hospital will receive 2 days of training in EAT before switching to the intervention condition. Training will be supplemented by ongoing supervision, coaching and a 2-month booster training provided by the research team. EAT is based on established behaviour change counselling methods, including motivational interviewing, cognitive–behavioural therapy, and incorporates clinical practice change theory. It is designed to improve motivation to eat despite a range of barriers (pain, mucositis, nausea, reduced or no saliva, taste changes and appetite loss), and to provide patients with practical behaviour change strategies. EAT will be delivered by dietitians during their usual consultations. 400 patients with HNC (nasopharynx, hypopharynx, oropharynx, oral cavity or larynx), aged 18+, undergoing radiotherapy (>60 Gy) with curative intent, will be recruited from radiotherapy departments at 5 Australian sites. Assessments will be conducted at 4 time points (first and final week of radiotherapy, 4 and 12 weeks postradiotherapy). The primary outcome will be a nutritional status assessment. Ethics and dissemination Ethics approval from all relevant bodies has been granted. Study findings will be disseminated widely through peer

  6. Mindfulness-based stress reduction (MBSR) as sole intervention for non-somatisation chronic non-cancer pain (CNCP): protocol for a systematic review and meta-analysis of randomised controlled trials

    PubMed Central

    Leung, Lawrence; Han, Han; Martin, Mary

    2015-01-01

    Introduction Chronic non-cancer pain (CNCP) affects up to 50% of the world's population. It impacts negatively on quality of life; entailing high costs on our medical systems, and translates to economic burden due to work loss. Aetiology of CNCP is complex and multifactorial, embracing the somatosensory, cognitive and affective domains. Opioid analgesia and other invasive interventions are often inadequate for clinical management of CNCP. Recently, mindfulness-based stress reduction (MBSR) has become a popular therapy for various medical conditions, including CNCP. However, studies reported varying efficacies, and relevant systematic reviews have included clinical trials with inherent heterogeneity either in study conditions or types of interventions used. Our study aims to provide an updated and more critical evaluation of the efficacy of MBSR as the intervention for non-somatisation CNCP. Methods and analysis A systematic review with meta-analysis of randomised controlled trials published in English will be performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines and the Cochrane Collaboration format. MEDLINE, EMBASE, PsychINFO, and the Cochrane Central Register of Controlled Trials Intervention, will be searched independently by reviewers using defined MeSH terms. Studies with full texts using MBSR as the main intervention on patients with non-somatising CNCP will be included. Outcome measures include pain scores and disability assessment scales. Continuous data will be meta-analysed using the RevMan 5 Review Manager programme. Primary analysis will adopt the random effects model in view of heterogeneity between trials. The standardised mean difference will be expressed as the effect size with 95% CIs. Forest plots, funnel plots, the I2 statistic and the Cochrane Risks of Bias Assessment table will be included. Ethics and dissemination No ethics approval is deemed necessary. Results of this study

  7. Evaluation of an early exercise intervention after thoracotomy for non-small cell lung cancer (NSCLC), effects on quality of life, muscle strength and exercise tolerance: randomised controlled trial.

    PubMed

    Arbane, Gill; Tropman, David; Jackson, David; Garrod, Rachel

    2011-02-01

    Deterioration in exercise tolerance and impairment in quality of life (QoL) are common consequences of lobectomy. This study evaluates additional exercise and strength training after lung resection on QoL, exercise tolerance and muscle strength. Fifty-three (28 male) patients attending thoracotomy for lung cancer, mean age, range 64 (32-82) years; mean pack years (SD) 31.9 (26.8); BMI 25.6 (4.2); FEV1 2.0 (0.7) l were randomised to control (usual care) or intervention (twice daily training plus usual care). After discharge the intervention group received monthly home visits and weekly telephone calls, the control group received monthly telephone calls up to 12 weeks. Assessment pre-operatively, 5 day and 12 weeks post-operatively consisted of quadriceps strength using magnetic stimulation, 6 Minute Walking Distance (6MWD) and QoL-EORTC-QLQ-LC13. QoL was unchanged over 12 weeks; 6MWD showed significant deterioration at 5 days post-operatively compared with pre-operatively, mean difference (SD)-131.6 (101.8) m and -128.0 (90.7) m in active and control groups respectively (p=0.89 between groups) which returned to pre-operative levels by 12 weeks in both groups. Quadriceps strength over the 5 day in-patient period showed a decrease of -8.3 (11.3) kg in the control group compared to increase of 4.0 (21.2) kg in the intervention group (p=0.04 between groups). Strength training after thoracotomy successfully prevented the fall in quadriceps strength seen in controls, however, there was no effect on 6MWD or QoL. 6MWD returned to pre-operative levels by 12 weeks regardless of additional support offered.

  8. Construction of single-chain variable fragment antibodies against MCF-7 breast cancer cells.

    PubMed

    Zuhaida, A A; Ali, A M; Tamilselvan, S; Alitheen, N B; Hamid, M; Noor, A M; Yeap, S K

    2013-11-18

    A phage display library of single chain variable fragment (scFv) against MCF-7 breast cancer cells was constructed from C3A8 hybridoma cells. RNA from the C3A8 was isolated, cDNA was constructed, and variable heavy and light immunoglobulin chain gene region were amplified using PCR. The variable heavy and light chain gene regions were combined with flexible linker, linked to a pCANTAB 5E phagemid vector and electrophoresed into supE strain of Escherichia coli TG1 cells. Forty-eight clones demonstrated positive binding activity to MCF-7 breast cancer cell membrane fragments and the strongest of 48 clones was selected for analysis. The anti-MCF-7 library evaluated by SfiI and NotI digests demonstrated that anti-MCF-7 scFv antibodies possess individual patterns that should be able to recognize distinct human breast cancer cells. The C3A8 scFv, with an apparent molecular weight of 32 kDa, showed high homology (99%) with single chain antibody against rice stripe virus protein P20. In summary, the anti MCF-7 scFv antibody can be used for pretargeting breast cancer for clinical diagnosis of patients; it also has potential for therapeutic applications.

  9. High-Resolution Mapping of Structural Mutations in Prostate Cancer with Single Nucleotide Polymorphism Arrays

    DTIC Science & Technology

    2006-11-01

    recurrent phyllodes tumor and fibroa- denoma of breast using single nucleotide polymorphism arrays. Breast Cancer Res Treat 2006; 97:301–309. 21...neutral LOH). Interestingly, copy-neutral LOH, which is undetectable by conventional CGH methods, represents up to 80% of LOH events in some tumor ...the notion that LOH represents a key mechanism for tumor suppressor inactivation. Indeed, nearly all common tumor suppressor genes occur in regions

  10. Application of single-cell genomics in cancer: promise and challenges.

    PubMed

    Wills, Quin F; Mead, Adam J

    2015-10-15

    Recent advances in single-cell genomics are opening up unprecedented opportunities to transform cancer genomics. While bulk tissue genomic analysis across large populations of tumour cells has provided key insights into cancer biology, this approach does not provide the resolution that is critical for understanding the interaction between different genetic events within the cellular hierarchy of the tumour during disease initiation, evolution, relapse and metastasis. Single-cell genomic approaches are uniquely placed to definitively unravel complex clonal structures and tissue hierarchies, account for spatiotemporal cell interactions and discover rare cells that drive metastatic disease, drug resistance and disease progression. Here we present five challenges that need to be met for single-cell genomics to fulfil its potential as a routine tool alongside bulk sequencing. These might be thought of as being challenges related to samples (processing and scale for analysis), sensitivity and specificity of mutation detection, sources of heterogeneity (biological and technical), synergies (from data integration) and systems modelling. We discuss these in the context of recent advances in technologies and data modelling, concluding with implications for moving cancer research into the clinic.

  11. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Gruppo Interegionale Cooperativo Oncologico Ginecologia.

    PubMed

    1987-08-15

    565 patients with stage III-IV epithelial ovarian cancer were randomly assigned to receive cisplatin (P), cyclophosphamide and cisplatin (CP), or cyclophosphamide, doxorubicin, and cisplatin (CAP). Data on 531 patients were analysed. Treatment with CAP resulted in a significantly higher overall (complete and partial) response rate (66 vs 56 vs 49% for CAP, CP, and P, respectively), but the rate of complete surgical response for the three treatment arms was similar (26, 21, and 20%). Size of residual tumour after first surgery and Karnofsky index were the best predictors of complete remission. Survival and disease-free survival were not significantly different in the three arms, although progression-free survival was significantly longer after CAP. However, tumour size, cell type, and Karnofsky index, but not therapy, were independent predictors for survival. Haematological toxicity was highest with CAP. The addition of cyclophosphamide or doxorubicin and cyclophosphamide to cisplatin does not substantially increase the number of potentially curable, advanced ovarian cancer patients.

  12. The Prognostic Impact of the Carcinoembryonic Antigen in Ampullary Cancer - A Retrospective Single Center Study

    PubMed Central

    Fuellgraf, Hannah; Schilling, Oliver; Lai, Zon Weng; Kulemann, Birte; Timme, Sylvia; Makowiec, Frank; Shahinian, Jasmin H.; Hoeppner, Jens; Werner, Martin; Hopt, Ulrich T.; Wellner, Ulrich F.; Bronsert, Peter

    2017-01-01

    Background: Carcinoembryonic antigen cell adhesion molecule (CEA) is a commonly immunohistochemically used antibody in pathological routine diagnostics with an overexpression in different cancers. We aimed to examine the immunohistochemically detectable CEA level in ampullary cancer and to correlate it with clinico-pathological data. Methods: Shot-gun proteomics revealed CEA in undifferentiated ampullary cancer cell lines. Next, tumor tissue of 40 ampullary cancers of a retrospective single center cohort of 40 patients was stained immunohistochemically for CEA; CEA expression was determined and correlated with clinico-pathological data. Results: Thirty-six patient specimens were included in statistical analysis. CEA expression and lymph node ratio (LNR) were the only independent predictors of overall survival in multivariate analysis. Conclusion: To our knowledge, cell line and patient cohorts are the largest and characterized cohorts examined for CEA so far. Hereby, CEA expression in ampullary cancer cells permits an estimation of outcome and suggests an opportunity for individualized CEA-directed therapy. Further trials with larger cohorts are needed to verify our results and to integrate CEA immunohistochemistry into clinical routine. PMID:28367245

  13. Multiple Breast Cancer Cell-Lines Derived from a Single Tumor Differ in Their Molecular Characteristics and Tumorigenic Potential

    PubMed Central

    Mosoyan, Goar; Nagi, Chandandeep; Marukian, Svetlana; Teixeira, Avelino; Simonian, Anait; Resnick-Silverman, Lois; DiFeo, Analisa; Johnston, Dean; Reynolds, Sandra R.; Roses, Daniel F.; Mosoian, Arevik

    2013-01-01

    Background Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient’s breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. Methods Five breast cancer cell lines were derived from a single patient’s primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER), CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC). In addition, a Fuorescent In Situ Hybridization (FISH) assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. Results We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. Conclusions All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to identify mechanisms

  14. Assessment of cancer care in Indian elderly cancer patients: A single center study

    PubMed Central

    Sarkar, Anindya; Shahi, UP

    2013-01-01

    Background and purpose: This prospective study aimed to assess the profiles of elderly cancer patient to optimize cancer care in Indian setup. The profiles have been compared with that of younger patients in terms of epidemiological, clinical data, co-morbidity, treatment, toxicity, clinical outcome, and survival pattern. Materials and Methods: The study comprised cancer patients attending radiotherapy outdoor (November 2005 to June 2006). There were 104 patients of age ≥60 years (elderly group) and 121 patients of 45-59 years (younger group). Results: Elderly group had median age 65 years (60-88 years) with M:F = 1:1. The younger group had median age 50 years (45-59 years) with M:F = 1:2. Elderly had higher proportion of gastrointestinal and genito-urinary tract malignancies. Younger group had higher proportion of breast, lymphoma, and brain tumor. 13% had co-morbidity, 50% received treatment, 27% were treated with radiotherapy with or without surgery, and two-third of these cases belong to elderly group. Majority tolerated treatment well. 10% had significant grade of toxicity. 57% of elderly patients did not accept and one-fourth of all cases did not complete the prescribed treatment. 88% cases were responders of which 70% showed complete response. There were no differences between two groups. At 12 months 35% of treated patients came for follow-up. At first 12 months, 60-70% were alive without disease. Conclusion: There were differences between two groups in terms of performance status, treatment acceptance, and treatment modality prescribed. Elderly patients deserve same opportunity as younger patients for treatment and survival options from the oncologist. PMID:24455630

  15. Single-walled carbon nanotubes as specific targeting and Raman spectroscopic agents for detection and discrimination of single human breast cancer cells

    NASA Astrophysics Data System (ADS)

    Nima, Zeid A.; Mahmood, Meena W.; Karmakar, Alokita; Mustafa, Thikra; Bourdo, Shawn; Xu, Yang; Biris, Alexandru S.

    2013-05-01

    Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) are prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized to bond covalently with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, which is specific to the highly expressed EpCAM antigen on the surface of breast cancer cells (MCF-7), but not on normal cells. The Raman nano-complexes demonstrate excellent ability to detect in vitro single breast cancer cells (MCF-7) and discriminate between them and normal fibroblast cells during the first 30 min of the targeting process. Raman linearity scanning is collected from a monolayer cell mixture, including both cancer cells and normal cells incubated with anti-EpCAM-SWCNTs, using a 633-nm laser excitation. The results shows that the Raman signal collected from targeted MCF-7 cells is extremely high, whereas there is little signal from the normal cells.

  16. Parallel Single Cancer Cell Whole Genome Amplification Using Button-Valve Assisted Mixing in Nanoliter Chambers

    PubMed Central

    Yang, Yoonsun; Swennenhuis, Joost F.; Rho, Hoon Suk; Le Gac, Séverine; Terstappen, Leon W. M. M.

    2014-01-01

    The heterogeneity of tumor cells and their alteration during the course of the disease urges the need for real time characterization of individual tumor cells to improve the assessment of treatment options. New generations of therapies are frequently associated with specific genetic alterations driving the need to determine the genetic makeup of tumor cells. Here, we present a microfluidic device for parallel single cell whole genome amplification (pscWGA) to obtain enough copies of a single cell genome to probe for the presence of treatment targets and the frequency of its occurrence among the tumor cells. Individual cells were first captured and loaded into eight parallel amplification units. Next, cells were lysed on a chip and their DNA amplified through successive introduction of dedicated reagents while mixing actively with the help of integrated button-valves. The reaction chamber volume for scWGA 23.85 nl, and starting from 6–7 pg DNA contained in a single cell, around 8 ng of DNA was obtained after WGA, representing over 1000-fold amplification. The amplified products from individual breast cancer cells were collected from the device to either directly investigate the amplification of specific genes by qPCR or for re-amplification of the DNA to obtain sufficient material for whole genome sequencing. Our pscWGA device provides sufficient DNA from individual cells for their genetic characterization, and will undoubtedly allow for automated sample preparation for single cancer cell genomic characterization. PMID:25233459

  17. Cancer Cell Analyses at the Single Cell-Level Using Electroactive Microwell Array Device

    PubMed Central

    Kobayashi, Marina; Kim, Soo Hyeon; Nakamura, Hiroko; Kaneda, Shohei; Fujii, Teruo

    2015-01-01

    Circulating tumor cells (CTCs), shed from primary tumors and disseminated into peripheral blood, are playing a major role in metastasis. Even after isolation of CTCs from blood, the target cells are mixed with a population of other cell types. Here, we propose a new method for analyses of cell mixture at the single-cell level using a microfluidic device that contains arrayed electroactive microwells. Dielectrophoretic (DEP) force, induced by the electrodes patterned on the bottom surface of the microwells, allows efficient trapping and stable positioning of single cells for high-throughput biochemical analyses. We demonstrated that various on-chip analyses including immunostaining, viability/apoptosis assay and fluorescent in situ hybridization (FISH) at the single-cell level could be conducted just by applying specific reagents for each assay. Our simple method should greatly help discrimination and analysis of rare cancer cells among a population of blood cells. PMID:26558904

  18. Single-cell SNP analyses and interpretations based on RNA-Seq data for colon cancer research.

    PubMed

    Chen, Jiahuan; Zhou, Qian; Wang, Yangfan; Ning, Kang

    2016-09-28

    Single-cell sequencing is useful for illustrating the cellular heterogeneities inherent in many intricate biological systems, particularly in human cancer. However, owing to the difficulties in acquiring, amplifying and analyzing single-cell genetic material, obstacles remain for single-cell diversity assessments such as single nucleotide polymorphism (SNP) analyses, rendering biological interpretations of single-cell omics data elusive. We used RNA-Seq data from single-cell and bulk colon cancer samples to analyze the SNP profiles for both structural and functional comparisons. Colon cancer-related pathways with single-cell level SNP enrichment, including the TGF-β and p53 signaling pathways, were also investigated based on both their SNP enrichment patterns and gene expression. We also detected a certain number of fusion transcripts, which may promote tumorigenesis, at the single-cell level. Based on these results, single-cell analyses not only recapitulated the SNP analysis results from the bulk samples but also detected cell-to-cell and cell-to-bulk variations, thereby aiding in early diagnosis and in identifying the precise mechanisms underlying cancers at the single-cell level.

  19. Can a print‐based intervention increase screening for first degree relatives of people with colorectal cancer? A randomised controlled trial

    PubMed Central

    Sanson‐Fisher, Robert; Macrae, Finlay; Cameron, Emilie; Hill, David; D'Este, Catherine; Simmons, Jody; Doran, Christopher

    2016-01-01

    Abstract Objective: To test the effectiveness of a targeted print‐based intervention to improve screening adherence in first degree relatives of people with colorectal cancer (CRC). Methods: People with CRC and their adult first degree relatives were identified through a population‐based cancer registry and randomly allocated as a family unit to the intervention or control condition. The control group received general information about CRC screening. The intervention group received printed advice regarding screening that was targeted to their risk level. Screening adherence was assessed at baseline and at 12 months via self report. Results: 752 (25%) index cases and 574 (34%) eligible first degree relatives consented to take part in the trial and completed baseline interviews. At 12 months, 58% of first degree relatives in the control group and 61% in the intervention group were adherent to screening guidelines (mixed effects logistic regression group by time interaction effect =2.7; 95%CI=1.2–5.9; P=0.013). Subgroup analysis indicated that the intervention was only effective for those with the lowest risk. Conclusions: Provision of personalised risk information may have a modest effect on adherence to CRC screening recommendations among first degree relatives of people diagnosed with CRC. Implications : Improved strategies for identifying and engaging first degree relatives are needed to maximise the population impact of the intervention. PMID:27625308

  20. Effects of Qi therapy (external Qigong) on symptoms of advanced cancer: a single case study.

    PubMed

    Lee, M S; Yang, S H; Lee, K K; Moon, S-R

    2005-12-01

    The aim of this study was to examine the effectiveness of Qi therapy (external Qigong) in the management of symptoms of advanced cancer in a man. We used a single case study design to evaluate the effectiveness of Qi therapy (external Qigong) in a 35-year-old man with advanced cancer (Stage IV) involving metastases in the stomach, lung and bone (Karnofsky performance scale: KPS, 40: requires special care and assistance, disabled). Treatment involved six days of pre-assessment, eight treatment sessions on alternate days over 16 days, and a two-week follow-up phase. A visual analogue scale (VAS) was used to assess the patient's self-reported symptoms of cancer over the intervention and follow-up periods. Following treatment, VAS scores' analysis revealed beneficial effects on pain, vomiting, dyspnoea, fatigue, anorexia, insomnia, daily activity and psychological calmness. These improvements were maintained over the two-week follow-up phase. After the first Qi therapy session, the patient discontinued medication and could sit by himself; after the fourth session, the patient was able to walk and use the toilet without assistance (improvement in KPS: 70: care for self, unable to perform normal activity or to do active work). Although limited by the single case study approach, our results support previous studies on this topic and provide reasons to conduct controlled clinical trials.

  1. Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

    PubMed

    Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

    2014-01-01

    It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

  2. The effects of oral zinc sulphate during radiotherapy on anti-oxidant enzyme activities in patients with head and neck cancer: a prospective, randomised, placebo-controlled study.

    PubMed

    Ertekin, M V; Koç, M; Karslioğlu, I; Sezen, O; Taysi, S; Bakan, N

    2004-07-01

    The purpose was to determine the effects of oral zinc sulphate along with radiotherapy on anti-oxidant enzyme activities in patients with head and neck cancer. Thirty patients with head and neck cancer were randomly assigned to receive either zinc sulphate capsules (including 50 mg zinc) (n = 15) or placebo (n = 15) three times a day, starting on the day of the first radiotherapy fraction and continuing throughout the scheduled radiotherapy course including weekends and 6 weeks after radiotherapy. The patients were treated with telecobalt radiation at conventional fractionation of 2 Gy/fraction and five fractions/ week in 20-35 fractions for a period of 4-7 weeks. Blood samples for biochemical parameters were collected after an overnight fast (12 h) before radiotherapy, the first day and 6 weeks after radiotherapy. In the placebo group, three patients were excluded. No difference was detected in any final measurement activities of erythrocyte anti-oxidant enzyme such as copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the direct comparison between the zinc sulphate and the placebo group, except erythrocyte SOD activities measured the first day after radiotherapy (p < 0.03). In the respective measurement analysis of the groups in themselves, in the zinc sulphate group, while the statistical analysis for the activities of erythrocyte CAT and GSH-Px were significantly different (chi2 = 12.4, p < 0.05; chi2 = 8.9, p < 0.05, respectively) before radiotherapy, the first day and 6 weeks after radiotherapy, the activities of SOD did not differ (chi2 = 4.2, p > 0.05). In these three measurements, there was no statistical significance in the activities of enzymes in erythrocyte Cu-Zn SOD, CAT and GSH-Px in the placebo group. Before radiotherapy, plasma zinc levels were normal in 16 patients (59.2%) and were lower in 11 patients (40.8%) compared with laboratory levels. It would be worthwhile studying the effect of oral zinc

  3. Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes

    PubMed Central

    2016-01-01

    In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo. PMID:27267364

  4. Polymer functionalized single walled carbon nanotubes mediated drug delivery of gliotoxin in cancer cells.

    PubMed

    Bhatnagar, Ira; Venkatesan, Jayachandran; Kiml, Se-Kwon

    2014-01-01

    During recent years, significant development has been achieved in carbon nanotube conjugated with polymer system for drug delivery system (DDS). In the present study, we have prepared functionalized single walled carbon nanotube conjugated with chitooligosaccharide (f-SWNT-COS) as a Drug Delivery System. In addition, drug Gliotoxin (GTX) and targeting molecules (Lysozyme, p53 and Folic acid) have been incorporated into f-SWNT-COS. f-SWNTs-COS-GTX-p53, f-SWNTs-COS-GTX-lysozyme, f-SWNTs-COS-GTX-FA have been physiochemically characterized for DDS. FT-IR, SEM and TEM analysis confirmed the formation of chemical interaction and polymer coating. FT-IR result clearly confirmed the interaction between f-SWNT and COS. The effective drug release was monitored against cervical cancer (HeLa) cells and Breast Cancer (MCF-7) cells and it was found that all the three drug delivery systems showed significant cytotoxicity. f-SWNTs-COS-GTX-p53 delivery vehicle and its effective cytotoxicity on HeLa cells was further checked with fluorescent activated cell sorter analysis. Our results suggest that the f-SWNTs-COS-GTX-p53 is the most effective delivery vehicle with a controlled release and enhanced cytotoxicity rendered through apoptosis in human cervical cancer (HeLa) cells. These systems can further be used for the delivery of other commercially available anti cancer drugs as well.

  5. Mitochondrial correlation microscopy and nanolaser spectroscopy - new tools for biophotonic detection of cancer in single cells.

    PubMed

    Gourley, Paul L; Hendricks, Judy K; McDonald, Anthony E; Copeland, R Guild; Barrett, Keith E; Gourley, Cheryl R; Singh, Keshav K; Naviaux, Robert K

    2005-12-01

    Currently, pathologists rely on labor-intensive microscopic examination of tumor cells using century-old staining methods that can give false readings. Emerging BioMicroNano-technologies have the potential to provide accurate, realtime, high-throughput screening of tumor cells without the need for time-consuming sample preparation. These rapid, nano-optical techniques may play an important role in advancing early detection, diagnosis, and treatment of disease. In this report, we show that laser scanning confocal microscopy can be used to identify a previously unknown property of certain cancer cells that distinguishes them, with single-cell resolution, from closely related normal cells. This property is the correlation of light scattering and the spatial organization of mitochondria. In normal liver cells, mitochondria are highly organized within the cytoplasm and highly scattering, yielding a highly correlated signal. In cancer cells, mitochondria are more chaotically organized and poorly scattering. These differences correlate with important bioenergetic disturbances that are hallmarks of many types of cancer. In addition, we review recent work that exploits the new technology of nanolaser spectroscopy using the biocavity laser to characterize the unique spectral signatures of normal and transformed cells. These optical methods represent powerful new tools that hold promise for detecting cancer at an early stage and may help to limit delays in diagnosis and treatment.

  6. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

    PubMed Central

    Saito, H.; Yoshizawa, H.; Yoshimori, K.; Katakami, N.; Katsumata, N.; Kawahara, M.; Eguchi, K.

    2013-01-01

    Background We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone. Patients and methods Patients receiving chemotherapy including cisplatin (≥70 mg/m2) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 μg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1–3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0–120 h). Results The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0–24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24–120 h postchemotherapy) phase (65% versus 49%, P = 0.0025). Conclusions Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin. PMID:23117073

  7. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    SciTech Connect

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-07-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation.

  8. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    DTIC Science & Technology

    2016-07-01

    profile of changes that occur in the bronchial epithelium in response to smoking, smoking cessation, and lung cancer. These discoveries may enhance...4. Impact…………………………...…………………………………… 13 5. Changes /Problems...….…………………………………………….. 13-14 6. Products…………………………………….……….….……………. 14 7...with lung cancer. These data will provide a comprehensive single cell transcriptional profile of changes that occur in the bronchial epithelium in

  9. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment†

    PubMed Central

    Whelan, J. S.; Bielack, S. S.; Marina, N.; Smeland, S.; Jovic, G.; Hook, J. M.; Krailo, M.; Anninga, J.; Butterfass-Bahloul, T.; Böhling, T.; Calaminus, G.; Capra, M.; Deffenbaugh, C.; Dhooge, C.; Eriksson, M.; Flanagan, A. M.; Gelderblom, H.; Goorin, A.; Gorlick, R.; Gosheger, G.; Grimer, R. J.; Hall, K. S.; Helmke, K.; Hogendoorn, P. C. W.; Jundt, G.; Kager, L.; Kuehne, T.; Lau, C. C.; Letson, G. D.; Meyer, J.; Meyers, P. A.; Morris, C.; Mottl, H.; Nadel, H.; Nagarajan, R.; Randall, R. L.; Schomberg, P.; Schwarz, R.; Teot, L. A.; Sydes, M. R.; Bernstein, M.; Pickering, James; Joffe, Nicola; Kevric, Matthias; Sorg, Benjamin; Villaluna, Doojduen; Wang, Caroline; Perisoglou, Martha; Trani, Leonardo; Potratz, Jenny; Carrle, Dorothe; Wilhelm, Miriam; Zils, Katja; Teske, Carmen

    2015-01-01

    Background Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. Patients and methods Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m2, doxorubicin 75 mg/m2, methotrexate 12 g/m2 × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. Results Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3–4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. Conclusions New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327. PMID:25421877

  10. Single centre outcomes from definitive chemo-radiotherapy and single modality radiotherapy for locally advanced oesophageal cancer

    PubMed Central

    Gray, Joanna; McDonald, Alexander; McIntosh, David; MacLaren, Vivienne; Hennessy, Aisling; Grose, Derek

    2016-01-01

    Background Definitive chemo-radiotherapy (dCRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years’ experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemo-radiotherapy (dCRT) or single modality radical radiotherapy (RT) with curative intent. Methods Retrospective analysis permitted identification of consecutive patients who underwent contemporary staging prior to non-surgical treatment for locally advanced oesophageal carcinoma. The primary outcomes were overall survival (OS) and disease-free survival (DFS), adjusted for baseline differences in age, tumour staging and histological cell type. All patients were treated with either dCRT or single modality RT within a single centre between 2009 and 2012. Results We identified 235 patients in total [median age 69.8 years, male =130 pts, female =105 pts, adenocarcinoma (ACA) =85 pts, squamous =150 pts]. A total of 190 pts received dCRT and 45 patients were treated with RT. All patients were staged with CT of chest, abdomen and pelvis, 226 patients underwent endoscopic ultrasound (EUS), and 183 patients had PET-CT. Patients treated with dCRT demonstrated longer OS (27 vs. 25 months respectively, P=0.02) and DFS (31 vs. 16 months respectively, P=0.01) compared to those treated with RT. More advanced tumour stage (stage 3 vs. stage 1/2) at presentation conferred poorer OS (32 vs. 38.2 months, P=0.02) and DFS (11 vs. 28 months, P=0.013). We demonstrated an acceptable toxicity profile with only 77 patients (32.8%) suffering grade 3 toxicity and 9 patients (4.2%) experiencing grade 4 toxicity by CTC criteria. The NG/PEG feeding rates were 4% across all treated patients. Conclusions This retrospective analysis is in keeping with current treatment paradigms emphasising the importance and safety of concurrent CRT in maximising curative potential for patients undergoing

  11. Prospective randomised trial of two dose levels of megestrol acetate in the management of anorexia-cachexia syndrome in patients with metastatic cancer.

    PubMed Central

    Gebbia, V.; Testa, A.; Gebbia, N.

    1996-01-01

    Two doses of megestrol acetate (MA) have been prospectively compared in a random fashion as treatment for cancer-related anorexia-cachexia syndrome (ACS) in 122 patients with progressive soft tissue sarcoma, colorectal, lung, head and neck and renal cancer resistant to systemic chemotherapy. After 30 days of MA, 55% of patients receiving MA at 160 mg day-1 reported an increase in appetite, 27% of patients no variation and 18% complained of a decrease in appetite. Patients treated with MA at 320 mg day-1 reported an increase in appetite in 68% of cases, a stabilisation in 20% of cases and a decrease in 12%. Although an increase in appetite was more frequently observed in patients receiving MA at 320 mg day-1, however this difference was not statistically significant (P = 0.305). After 30 days of MA, 31% of patients treated with MA at 160 mg day-1 showed an increase in body weight, 25% a stabilisation and 44% a decrease. In the group of patients treated with MA at 320 mg day-1, 45% reported an increase in body weight, 16% no change and 23% weight loss. Although there was a trend favouring the higher dose of MA, overall analysis however failed to detect any statistically significant difference between the two treatment arms (P = 0.242). Twenty-seven patients pretreated with 160 mg day-1 and 23 patients treated with 320 mg day-1 received further therapy with MA at the dose of 320 and 480 mg day-1 respectively. In the group of 22 patients treated with 320 mg day-1 four (18%) reported an increase in body weight, eight (36%) an improvement in appetite, but none had an increase in performance status. Among the 20 evaluable patients treated with 480 mg day-1, two (10%) had an increase in body weight, four (20%) an improvement in appetite, but none reported an increase in performance status. No difference in median survival was detected between the two arms. Toxicity was mild and predictable. In conclusion, the data achieved in the present study confirm the clinical safety

  12. Transanal Total Mesorectal Excision With Single-Incision Laparoscopy for Rectal Cancer

    PubMed Central

    Foo, Dominic Chi-chung; Choi, Hok Kwok; Wei, Rockson; Yip, Jeremy

    2016-01-01

    Background and Objectives: There has been great enthusiasm for the technique of transanal total mesorectal excision. Coupled with this procedure, we performed single-incision laparoscopic surgery for left colon mobilization. This is a description of our initial experience with the combined approach. Methods: Patients with distal or mid rectal cancer were included. The operation was performed by 2 teams: one team performed the single-incision mobilization of the left colon via the right lower quadrant ileostomy site, and the other team performed the total mesorectal excision with a transanal platform. Results: During the study period, 10 patients (5 men) with cancer of the rectum underwent the surgery. The mean age was 62.2 ± 11.1 years, and the mean body mass index was 23.4 ± 3.2 kg/m2. The tumor's mean distance from the anal verge was 5.1 ± 2.5 cm. The median operating time was 247.5 minutes (range, 188–462 minutes). The mean estimated blood loss was 124 ± 126 mL (range, 10–188 mL). Conversion to multiport laparoscopy was needed in one case (10%). Postoperative pain, as reflected by the pain score, was minimal. The mean number of lymph nodes harvested was 15.6 ± 3.8. All specimens had clear distal and circumferential radial margins. The overall complication rate was 10%. Conclusion: Our experience showed transanal total mesorectal excision with single-incision laparoscopy to be a feasible option for rectal cancer. Patients reported minimal postoperative pain. Further studies on the long-term outcome are warranted. PMID:27186068

  13. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells.

    PubMed

    Lawson, Devon A; Bhakta, Nirav R; Kessenbrock, Kai; Prummel, Karin D; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-10-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated

  14. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials

    PubMed Central

    Earl, H M; Hiller, L; Dunn, J A; Vallier, A-L; Bowden, S J; Jordan, S D; Blows, F; Munro, A; Bathers, S; Grieve, R; Spooner, D A; Agrawal, R; Fernando, I; Brunt, A M; O'Reilly, S M; Crawford, S M; Rea, D W; Simmonds, P; Mansi, J L; Stanley, A; McAdam, K; Foster, L; Leonard, R CF; Twelves, C J; Cameron, D; Bartlett, J MS; Pharoah, P; Provenzano, E; Caldas, C; Poole, C J

    2012-01-01

    Background: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. Methods: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. Results: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65–0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65–0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. Conclusion: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival. PMID:23047592

  15. Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

    PubMed Central

    Quenel-Tueux, Nathalie; Debled, Marc; Rudewicz, Justine; MacGrogan, Gaetan; Pulido, Marina; Mauriac, Louis; Dalenc, Florence; Bachelot, Thomas; Lortal, Barbara; Breton-Callu, Christelle; Madranges, Nicolas; de Lara, Christine Tunon; Fournier, Marion; Bonnefoi, Hervé; Soueidan, Hayssam; Nikolski, Macha; Gros, Audrey; Daly, Catherine; Wood, Henry; Rabbitts, Pamela; Iggo, Richard

    2015-01-01

    Background: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. Methods: One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment. Results: A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles. Conclusions: Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients. PMID:26171933

  16. Neglected tropical diseases: survey and geometry of randomised evidence

    PubMed Central

    Kappagoda, Shanthi

    2012-01-01

    Objective To assess the quantity and distribution of evidence from randomised controlled trials for the treatment of the major neglected tropical diseases and to identify gaps in the evidence with network analysis. Design Systematic review and network analysis. Data sources Cochrane Central Register of Controlled Trials and PubMed from inception to 31 August 2011. Study selection Randomised controlled trials that examined treatment of 16 neglected tropical diseases or complications thereof published in English, French, Spanish, Portuguese, German, or Dutch. Results We identified 971 eligible randomised trials. Leishmaniasis (184 trials, 23 039 participants) and geohelminth infections; 160 trials, 46 887 participants) were the most studied, while dracunculiasis (nine trials, 798 participants) and Buruli ulcer (five trials, 337 participants) were least studied. Relative to its global burden of disease, lymphatic filariasis had the fewest trials and participants. Only 11% of trials were industry funded. Either a single trial or trials with fewer than 100 participants comprised the randomised evidence for first or second line treatments for Buruli ulcer, human African trypanosomiasis, American trypanosomiasis, cysticercosis, rabies, echinococcosis, New World cutaneous leishmaniasis, and each of the foodborne trematode infections. Among the 10 disease categories with more than 40 trials, five lacked sufficient head to head comparisons between first or second line treatments. Conclusions There is considerable variation in the amount of evidence from randomised controlled trials for each of the 16 major neglected tropical diseases. Even in diseases with substantial evidence, such as leishmaniasis and geohelminth infections, some recommended treatments have limited supporting data and lack head to head comparisons. PMID:23089149

  17. Microfluidic device for mechanical dissociation of cancer cell aggregates into single cells

    PubMed Central

    Pennell, Marissa; Troiani, Marco; Haun, Jered B.

    2014-01-01

    Tumors tissues house a diverse array of cell types, requiring powerful cell-based analysis methods to characterize different cell subtypes. Tumor tissue is dissociated into single cells by treatment with proteolytic enzymes, followed by mechanical disruption using vortexing or pipetting. These procedures can be incomplete and require significant time, and the latter mechanical treatments are poorly defined and controlled. Here, we present a novel microfluidic device to improve mechanical dissociation of digested tissue and cell aggregates into single cells. The device design includes a network of branching channels that range in size from millimeters down to hundreds of microns. The channels also contain flow constrictions that generate well-defined regions of high shear force, which we refer to as “hydrodynamic micro-scalpels,” to progressively disaggregate tissue fragments and clusters into single cells. We show using in vitro cancer cell models that the microfluidic device significantly enhances cell recovery in comparison to mechanical disruption by pipetting and vortexing digestion with trypsin or incubation with EDTA. Notably, the device enabled superior results to be obtained after shorter proteolytic digestion times, resulting in fully viable cells in less than ten minutes. The device could also be operated under enzyme-free conditions that could better maintain expression of certain surface markers. The microfluidic format is advantageous because it enables application of well-defined mechanical forces and rapid processing times. Furthermore, it may be possible to directly integrate downstream processing and detection operations to create integrated cell-based analysis platforms. The enhanced capabilities enabled by our novel device may help promote applications of single cell detection and purification techniques to tumor tissue specimens, advancing the current understanding of cancer biology and enabling molecular diagnostics in clinical settings

  18. Microfluidic device for mechanical dissociation of cancer cell aggregates into single cells.

    PubMed

    Qiu, Xiaolong; De Jesus, Janice; Pennell, Marissa; Troiani, Marco; Haun, Jered B

    2015-01-07

    Tumors tissues house a diverse array of cell types, requiring powerful cell-based analysis methods to characterize cellular heterogeneity and identify rare cells. Tumor tissue is dissociated into single cells by treatment with proteolytic enzymes, followed by mechanical disruption using vortexing or pipetting. These procedures can be incomplete and require significant time, and the latter mechanical treatments are poorly defined and controlled. Here, we present a novel microfluidic device to improve mechanical dissociation of digested tissue and cell aggregates into single cells. The device design includes a network of branching channels that range in size from millimeters down to hundreds of microns. The channels also contain flow constrictions that generate well-defined regions of high shear force, which we refer to as "hydrodynamic micro-scalpels", to progressively disaggregate tissue fragments and clusters into single cells. We show using in vitro cancer cell models that the microfluidic device significantly enhances cell recovery in comparison to mechanical disruption by pipetting and vortexing after digestion with trypsin or incubation with EDTA. Notably, the device enabled superior results to be obtained after shorter proteolytic digestion times, resulting in fully viable cells in less than ten minutes. The device could also be operated under enzyme-free conditions that could better maintain expression of certain surface markers. The microfluidic format is advantageous because it enables application of well-defined mechanical forces and rapid processing times. Furthermore, it may be possible to directly integrate downstream processing and detection operations to create integrated cell-based analysis platforms. The enhanced capabilities enabled by our novel device may help promote applications of single cell detection and purification techniques to tumor tissue specimens, advancing the current understanding of cancer biology and enabling molecular diagnostics

  19. Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

    PubMed

    Suresh, S; Spatz, J; Mills, J P; Micoulet, A; Dao, M; Lim, C T; Beil, M; Seufferlein, T

    2005-01-01

    We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation

  20. Reprint of: Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

    PubMed

    Suresh, S; Spatz, J; Mills, J P; Micoulet, A; Dao, M; Lim, C T; Beil, M; Seufferlein, T

    2015-09-01

    We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation

  1. Fluorescent metal nanoshell probe to detect single miRNA in lung cancer cell.

    PubMed

    Zhang, Jian; Fu, Yi; Mei, Yuping; Jiang, Feng; Lakowicz, Joseph R

    2010-06-01

    In this study, fluorescent metal nanoshells were synthesized as a molecular imaging agent to detect single microRNA (miRNA) molecules in the cells positive to lung cancer. These metal nanoshells were composed of silica spheres with encapsulated Ru(bpy)(3)(2+) complexes as cores and thin silver layers as shells. Compared with the silica spheres in the absence of metal, the metal nanoshells displayed an enhanced emission intensity, shortened lifetime, and extended photostability. The single-stranded probe oligonucleotides were covalently bound on the metal nanoshells to hybridize with the target miRNA-486 molecules in the cells. It was shown that with stronger emission intensity and longer lifetime, the conjugated metal nanoshells were isolated distinctly from the cellular autofluorescence on the cell images. These emission spots on the cell images were counted accurately and analyzed with a pool of cells representing the miRNA-486 expression levels in the cells. The results may reflect a genomic signal change and provide a reference to lung cancer early diagnosis as well as other diseases.

  2. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    SciTech Connect

    Felthaus, O.; Ettl, T.; Gosau, M.; Driemel, O.; Brockhoff, G.; Reck, A.; Zeitler, K.; Hautmann, M.; Reichert, T.E.; Schmalz, G.; Morsczeck, C.

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  3. Molecular Genetic Characterization of Individual Cancer Cells Isolated via Single-Cell Printing.

    PubMed

    Riba, Julian; Renz, Nathalie; Niemöller, Christoph; Bleul, Sabine; Pfeifer, Dietmar; Stosch, Juliane M; Metzeler, Klaus H; Hackanson, Björn; Lübbert, Michael; Duyster, Justus; Koltay, Peter; Zengerle, Roland; Claus, Rainer; Zimmermann, Stefan; Becker, Heiko

    Intratumoral genetic heterogeneity may impact disease outcome. Gold standard for dissecting clonal heterogeneity are single-cell analyses. Here, we present an efficient workflow based on an advanced Single-Cell Printer (SCP) device for the study of gene variants in single cancer cells. To allow for precise cell deposition into microwells the SCP was equipped with an automatic dispenser offset compensation, and the 384-microwell plates were electrostatically neutralized. The ejection efficiency was 99.7% for fluorescent beads (n = 2304) and 98.7% for human cells (U-2 OS or Kasumi-1 cancer cell line, acute myeloid leukemia [AML] patient; n = 150). Per fluorescence microscopy, 98.8% of beads were correctly delivered into the wells. A subset of single cells (n = 81) was subjected to whole genome amplification (WGA), which was successful in all cells. On empty droplets, a PCR on LINE1 retrotransposons yielded no product after WGA, verifying the absence of free-floating DNA in SCP-generated droplets. Representative gene variants identified in bulk specimens were sequenced in single-cell WGA DNA. In U-2 OS, 22 of 25 cells yielded results for both an SLC34A2 and TET2 mutation site, including cells harboring the SLC34A2 but not the TET2 mutation. In one cell, the TET2 mutation analysis was inconclusive due to allelic dropout, as assessed via polymorphisms located close to the mutation. Of Kasumi-1, 23 of 33 cells with data on both the KIT and TP53 mutation site harbored both mutations. In the AML patient, 21 of 23 cells were informative for a TP53 polymorphism; the identified alleles matched the loss of chromosome arm 17p. The advanced SCP allows efficient, precise and gentle isolation of individual cells for subsequent WGA and routine PCR/sequencing-based analyses of gene variants. This makes single-cell information readily accessible to a wide range of applications and can provide insights into clonal heterogeneity that were indeterminable solely by analyses of bulk

  4. Molecular Genetic Characterization of Individual Cancer Cells Isolated via Single-Cell Printing

    PubMed Central

    Riba, Julian; Renz, Nathalie; Niemöller, Christoph; Bleul, Sabine; Pfeifer, Dietmar; Stosch, Juliane M.; Metzeler, Klaus H.; Hackanson, Björn; Lübbert, Michael; Duyster, Justus; Koltay, Peter; Zengerle, Roland; Claus, Rainer

    2016-01-01

    Intratumoral genetic heterogeneity may impact disease outcome. Gold standard for dissecting clonal heterogeneity are single-cell analyses. Here, we present an efficient workflow based on an advanced Single-Cell Printer (SCP) device for the study of gene variants in single cancer cells. To allow for precise cell deposition into microwells the SCP was equipped with an automatic dispenser offset compensation, and the 384-microwell plates were electrostatically neutralized. The ejection efficiency was 99.7% for fluorescent beads (n = 2304) and 98.7% for human cells (U-2 OS or Kasumi-1 cancer cell line, acute myeloid leukemia [AML] patient; n = 150). Per fluorescence microscopy, 98.8% of beads were correctly delivered into the wells. A subset of single cells (n = 81) was subjected to whole genome amplification (WGA), which was successful in all cells. On empty droplets, a PCR on LINE1 retrotransposons yielded no product after WGA, verifying the absence of free-floating DNA in SCP-generated droplets. Representative gene variants identified in bulk specimens were sequenced in single-cell WGA DNA. In U-2 OS, 22 of 25 cells yielded results for both an SLC34A2 and TET2 mutation site, including cells harboring the SLC34A2 but not the TET2 mutation. In one cell, the TET2 mutation analysis was inconclusive due to allelic dropout, as assessed via polymorphisms located close to the mutation. Of Kasumi-1, 23 of 33 cells with data on both the KIT and TP53 mutation site harbored both mutations. In the AML patient, 21 of 23 cells were informative for a TP53 polymorphism; the identified alleles matched the loss of chromosome arm 17p. The advanced SCP allows efficient, precise and gentle isolation of individual cells for subsequent WGA and routine PCR/sequencing-based analyses of gene variants. This makes single-cell information readily accessible to a wide range of applications and can provide insights into clonal heterogeneity that were indeterminable solely by analyses of bulk

  5. Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

    PubMed Central

    Sellers, Thomas A.; Huang, Yifan; Cunningham, Julie; Goode, Ellen L.; Sutphen, Rebecca; Vierkant, Robert A.; Kelemen, Linda E.; Fredericksen, Zachary S.; Liebow, Mark; Pankratz, V. Shane; Hartmann, Lynn C.; Myer, Jeff; Iversen, Edwin S.; Schildkraut, Joellen M.; Phelan, Catherine

    2012-01-01

    Studies suggest that underglycosylation of the cell membrane mucin MUC1 may be associated with epithelial ovarian cancer. We identified 26 genes involved in glycosylation and examined 93 single nucleotide polymorphisms (SNP) with a minor allele frequency of ≥0.05 in relation to incident ovarian cancer. Cases were ascertained at the Mayo Clinic, Rochester, MN (n = 396) or a 48-county region in North Carolina (Duke University; n = 534). Ovarian cancer- free controls (n = 1,037) were frequency matched to the cases on age, race, and residence. Subjects were interviewed to obtain data on risk factors and a sample of blood for DNA and genotyped using the Illumina GoldenGate assay. We excluded subjects and individual SNPs with genotype call rates of <90%. Data were analyzed using logistic regression, with adjustment for age and residence. We fitted dominant, log additive, and recessive genetic models. Among Caucasians, nine SNPs in eight genes were associated with risk at P < 0.05 under at least one genetic model before adjusting for multiple testing. A SNP in GALNT1 (rs17647532) was the only one that remained statistically significant after Bonferroni adjustment for multiple testing but was not statistically significant in Hardy-Weinberg equilibrium among controls. Haplo-type analyses revealed a global association of GALNT1 with risk (P = 0.038, under a recessive genetic model), which largely reflected a decreased risk of one haplotype (0.10 frequency; odds ratio, 0.07; P = 0.01) compared with the most common haplotype (0.39 frequency). These results suggest that genetic polymorphisms in the glycoslyation process may be novel risk factors for ovarian cancer. PMID:18268124

  6. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    PubMed Central

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I; Fizazi, Karim; Bossi, Alberto; van den Eertwegh, Alfons J M; Krainer, Michael; Houede, Nadine; Santos, Ricardo; Mahammedi, Hakim; Ng, Siobhan; Maio, Michele; Franke, Fabio A; Sundar, Santhanam; Agarwal, Neeraj; Bergman, Andries M; Ciuleanu, Tudor E; Korbenfeld, Ernesto; Sengeløv, Lisa; Hansen, Steinbjorn; Logothetis, Christopher; Beer, Tomasz M; McHenry, M Brent; Gagnier, Paul; Liu, David; Gerritsen, Winald R

    2015-01-01

    Summary Background Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy. Methods We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8 Gy in one fraction) followed by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by Eastern Cooperative Oncology Group performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. The primary endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. Findings From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the intention-to-treat analysis. Median overall survival was 11·2 months (95% CI 9·5–12·7) with ipilimumab and 10·0 months (8·3–11·0) with placebo (hazard ratio [HR] 0·85, 0·72–1·00; p=0·053). However, the assessment of the proportional hazards assumption showed that it was violated (p=0·0031). A piecewise hazard model showed that the HR changed over time: the HR for 0–5 months was 1·46 (95% CI 1·10–1·95), for 5–12 months was 0·65 (0·50–0·85), and

  7. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer.

    PubMed

    Geraets, Daan; Alemany, Laia; Guimera, Nuria; de Sanjose, Silvia; de Koning, Maurits; Molijn, Anco; Jenkins, David; Bosch, Xavier; Quint, Wim

    2012-12-01

    The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR-DEIA-LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role.

  8. Microfluidic chip with integrated electrical cell-impedance sensing for monitoring single cancer cell migration in three-dimensional matrixes.

    PubMed

    Nguyen, Tien Anh; Yin, Tsung-I; Reyes, Diego; Urban, Gerald A

    2013-11-19

    Cell migration has been recognized as one hallmark of malignant tumor progression. By integrating the method of electrical cell-substrate impedance sensing (ECIS) with the Boyden chamber design, the state-of-the-art techniques provide kinetic information about cell migration and invasion processes in three-dimensional (3D) extracellular matrixes. However, the information related to the initial stage of cell migration with single-cell resolution, which plays a unique role in the metastasis-invasion cascade of cancer, is not yet available. In this paper, we present a microfluidic device integrated with ECIS for investigating single cancer cell migration in 3D matrixes. Using microfluidics techniques without the requirement of physical connections to off-chip pneumatics, the proposed sensor chip can efficiently capture single cells on microelectrode arrays for sequential on-chip 2D or 3D cell culture and impedance measurement. An on-chip single-cell migration assay was successfully demonstrated within several minutes. Migration of single metastatic MDA-MB-231 cells in their initial stage can be monitored in real time; it shows a rapid change in impedance magnitude of approximately 10 Ω/s, whereas no prominent impedance change is observed for less-metastasis MCF-7 cells. The proposed sensor chip, allowing for a rapid and selective detection of the migratory properties of cancer cells at the single-cell level, could be applied as a new tool for cancer research.

  9. Cost-Effectiveness of Double Reading versus Single Reading of Mammograms in a Breast Cancer Screening Programme

    PubMed Central

    Posso, Margarita; Carles, Misericòrdia; Rué, Montserrat; Puig, Teresa; Bonfill, Xavier

    2016-01-01

    Objectives The usual practice in breast cancer screening programmes for mammogram interpretation is to perform double reading. However, little is known about its cost-effectiveness in the context of digital mammography. Our purpose was to evaluate the cost-effectiveness of double reading versus single reading of digital mammograms in a population-based breast cancer screening programme. Methods Data from 28,636 screened women was used to establish a decision-tree model and to compare three strategies: 1) double reading; 2) double reading for women in their first participation and single reading for women in their subsequent participations; and 3) single reading. We calculated the incremental cost-effectiveness ratio (ICER), which was defined as the expected cost per one additionally detected cancer. We performed a deterministic sensitivity analysis to test the robustness of the ICER. Results The detection rate of double reading (5.17‰) was similar to that of single reading (4.78‰; P = .768). The mean cost of each detected cancer was €8,912 for double reading and €8,287 for single reading. The ICER of double reading versus single reading was €16,684. The sensitivity analysis showed variations in the ICER according to the sensitivity of reading strategies. The strategy that combines double reading in first participation with single reading in subsequent participations was ruled out due to extended dominance. Conclusions From our results, double reading appears not to be a cost-effective strategy in the context of digital mammography. Double reading would eventually be challenged in screening programmes, as single reading might entail important net savings without significantly changing the cancer detection rate. These results are not conclusive and should be confirmed in prospective studies that investigate long-term outcomes like quality adjusted life years (QALYs). PMID:27459663

  10. Single Cell Proteolytic Assays to Investigate Cancer Clonal Heterogeneity and Cell Dynamics Using an Efficient Cell Loading Scheme

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Chih; Cheng, Yu-Heng; Ingram, Patrick; Yoon, Euisik

    2016-06-01

    Proteolytic degradation of the extracellular matrix (ECM) is critical in cancer invasion, and recent work suggests that heterogeneous cancer populations cooperate in this process. Despite the importance of cell heterogeneity, conventional proteolytic assays measure average activity, requiring thousands of cells and providing limited information about heterogeneity and dynamics. Here, we developed a microfluidic platform that provides high-efficiency cell loading and simple valveless isolation, so the proteolytic activity of a small sample (10–100 cells) can be easily characterized. Combined with a single cell derived (clonal) sphere formation platform, we have successfully demonstrated the importance of microenvironmental cues for proteolytic activity and also investigated the difference between clones. Furthermore, the platform allows monitoring single cells at multiple time points, unveiling different cancer cell line dynamics in proteolytic activity. The presented tool facilitates single cell proteolytic analysis using small samples, and our findings illuminate the heterogeneous and dynamic nature of proteolytic activity.

  11. Single Cell Proteolytic Assays to Investigate Cancer Clonal Heterogeneity and Cell Dynamics Using an Efficient Cell Loading Scheme

    PubMed Central

    Chen, Yu-Chih; Cheng, Yu-Heng; Ingram, Patrick; Yoon, Euisik

    2016-01-01

    Proteolytic degradation of the extracellular matrix (ECM) is critical in cancer invasion, and recent work suggests that heterogeneous cancer populations cooperate in this process. Despite the importance of cell heterogeneity, conventional proteolytic assays measure average activity, requiring thousands of cells and providing limited information about heterogeneity and dynamics. Here, we developed a microfluidic platform that provides high-efficiency cell loading and simple valveless isolation, so the proteolytic activity of a small sample (10–100 cells) can be easily characterized. Combined with a single cell derived (clonal) sphere formation platform, we have successfully demonstrated the importance of microenvironmental cues for proteolytic activity and also investigated the difference between clones. Furthermore, the platform allows monitoring single cells at multiple time points, unveiling different cancer cell line dynamics in proteolytic activity. The presented tool facilitates single cell proteolytic analysis using small samples, and our findings illuminate the heterogeneous and dynamic nature of proteolytic activity. PMID:27283981

  12. DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.

    PubMed

    Liu, Lin; De, Subhajyoti; Michor, Franziska

    2013-01-01

    Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes. Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features. Furthermore, some substitution signatures are more frequent in certain DNA replication timing zones. Finally, integrating data on higher-order nuclear organization, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves. These data suggest that DNA replication timing together with higher-order genomic organization contribute to the patterns of single-nucleotide substitution in normal and cancer genomes.

  13. Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing.

    PubMed

    Yu, Chang; Yu, Jun; Yao, Xiaotian; Wu, William K K; Lu, Youyong; Tang, Senwei; Li, Xiangchun; Bao, Li; Li, Xiaoxing; Hou, Yong; Wu, Renhua; Jian, Min; Chen, Ruoyan; Zhang, Fan; Xu, Lixia; Fan, Fan; He, Jun; Liang, Qiaoyi; Wang, Hongyi; Hu, Xueda; He, Minghui; Zhang, Xiang; Zheng, Hancheng; Li, Qibin; Wu, Hanjie; Chen, Yan; Yang, Xu; Zhu, Shida; Xu, Xun; Yang, Huanming; Wang, Jian; Zhang, Xiuqing; Sung, Joseph J Y; Li, Yingrui; Wang, Jun

    2014-06-01

    Single-cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management. Here we performed single-cell sequencing analysis of a case of colon cancer. Population genetics analyses identified two independent clones in tumor cell population. The major tumor clone harbored APC and TP53 mutations as early oncogenic events, whereas the minor clone contained preponderant CDC27 and PABPC1 mutations. The absence of APC and TP53 mutations in the minor clone supports that these two clones were derived from two cellular origins. Examination of somatic mutation allele frequency spectra of additional 21 whole-tissue exome-sequenced cases revealed the heterogeneity of clonal origins in colon cancer. Next, we identified a mutated gene SLC12A5 that showed a high frequency of mutation at the single-cell level but exhibited low prevalence at the population level. Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer. Our study provides the first exome-wide evidence at single-cell level supporting that colon cancer could be of a biclonal origin, and suggests that low-prevalence mutations in a cohort may also play important protumorigenic roles at the individual level.

  14. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    PubMed Central

    2012-01-01

    Background Cancers arise through an evolutionary process in which cell populations are subjected to selection; however, to date, the process of bladder cancer, which is one of the most common cancers in the world, remains unknown at a single-cell level. Results We carried out single-cell exome sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively. Conclusions This work provides a new approach of investigating the genetic details of bladder tumoral changes at the single-cell level and a new method for assessing bladder cancer evolution at a cell-population level. PMID:23587365

  15. Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing

    PubMed Central

    Yu, Chang; Yu, Jun; Yao, Xiaotian; Wu, William KK; Lu, Youyong; Tang, Senwei; Li, Xiangchun; Bao, Li; Li, Xiaoxing; Hou, Yong; Wu, Renhua; Jian, Min; Chen, Ruoyan; Zhang, Fan; Xu, Lixia; Fan, Fan; He, Jun; Liang, Qiaoyi; Wang, Hongyi; Hu, Xueda; He, Minghui; Zhang, Xiang; Zheng, Hancheng; Li, Qibin; Wu, Hanjie; Chen, Yan; Yang, Xu; Zhu, Shida; Xu, Xun; Yang, Huanming; Wang, Jian; Zhang, Xiuqing; Sung, Joseph JY; Li, Yingrui; Wang, Jun

    2014-01-01

    Single-cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management. Here we performed single-cell sequencing analysis of a case of colon cancer. Population genetics analyses identified two independent clones in tumor cell population. The major tumor clone harbored APC and TP53 mutations as early oncogenic events, whereas the minor clone contained preponderant CDC27 and PABPC1 mutations. The absence of APC and TP53 mutations in the minor clone supports that these two clones were derived from two cellular origins. Examination of somatic mutation allele frequency spectra of additional 21 whole-tissue exome-sequenced cases revealed the heterogeneity of clonal origins in colon cancer. Next, we identified a mutated gene SLC12A5 that showed a high frequency of mutation at the single-cell level but exhibited low prevalence at the population level. Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer. Our study provides the first exome-wide evidence at single-cell level supporting that colon cancer could be of a biclonal origin, and suggests that low-prevalence mutations in a cohort may also play important protumorigenic roles at the individual level. PMID:24699064

  16. Plasmonics nanoprobes: detection of single-nucleotide polymorphisms in the breast cancer BRCA1 gene.

    PubMed

    Wabuyele, Musundi B; Yan, Fei; Vo-Dinh, Tuan

    2010-09-01

    This paper describes the application of plasmonics-based nanoprobes that combine the modulation of the plasmonics effect to change the surface-enhanced Raman scattering (SERS) of a Raman label and the specificity of a DNA hairpin loop sequence to recognize and discriminate a variety of molecular target sequences. Hybridization with target DNA opens the hairpin and physically separates the Raman label from the metal nanoparticle thus reducing the plasmonics effect and quenching the SERS signal of the label. We have successfully demonstrated the specificity and selectivity of the nanoprobes in the detection of a single-nucleotide polymorphism (SNP) in the breast cancer BRCA1 gene in a homogenous solution at room temperature. In addition, the potential application of plasmonics nanoprobes for quantitative DNA diagnostic testing is discussed.

  17. Single fiber beta detector for stereotactic biopsy and intraoperative lumpectomy of breast cancer

    SciTech Connect

    Atac, M.; Nalcioglu, O.; Roeck, W.W.

    1996-10-01

    We have developed an intraoperative probe for use in early detection of breast cancer and aiding lumpectomy. The probe consists of a small plastic scintillator, 0.8mm dia and 3mm long, coupled to a single clear optical-fiber strand, and solid state photomultiplier. Due to the small size of the probe, it can be placed inside of a small gauge biopsy needle. The scintillator is very efficient in detecting betas and positrons while being very in efficient to energetic gammas due to small size and low density. High quantum efficiency, 80%, and high gain obtainable, solid state photomultiplier makes the probe very low noise device in detecting beta particles. Intrinsic resolution of the probe is expected to be around 1 mm. Preliminary results using beta sources and a rat bearing R320 adenocarcinoma tumor were very successful.

  18. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A Single-Institution Matched-Pair Analysis

    SciTech Connect

    Pickles, Tom; Keyes, Mira; Morris, W. James

    2010-01-15

    Purpose: In the absence of randomized study data, institutional case series have shown brachytherapy (BT) to produce excellent biochemical control (bNED) in patients with localized prostate cancer compared with alternative curative treatments. This study was designed to overcome some of the limitations of case series studies by using a matched-pair design in patients treated contemporaneously with BT and external beam radiation therapy (EBRT) at a single institution. Methods and Materials: Six hundred one eligible patients treated between 1998 and 2001 were prospectively followed up in our institutional databases and matched on a 1:1 basis for the following known prognostic variables: prostate-specific antigen (PSA) level, Gleason score, T stage, the use and duration of neoadjuvant androgen deprivation therapy, and the percentage of positive tissue core samples. Two hundred seventy-eight perfect matches of patients (139 in each group) with low- and intermediate-risk cancer were further analyzed. bNED (Phoenix definition) was the primary endpoint. Other endpoints were toxicity, PSA kinetics, and the secondary use of androgen deprivation therapy. Results: The 5-year bNED rates were 95% (BT) and 85% (EBRT) (p < 0.001). After 7 years, the BT bNED result was unchanged, but the rate in EBRT patients had fallen to 75%. The median posttreatment PSA nadirs were 0.04 ng/mL (BT) and 0.62 ng/mL (EBRT, p < 0.001), which predicted a higher ongoing treatment failure rate in association with EBRT use than with BT use. Late urinary toxicity and rectal/bowel toxicity were worse in patients treated with BT and EBRT, respectively. Conclusions: BT for both low-risk and selected intermediate-risk cancers achieves exceptional cure rates. Even with dose escalation, it will be difficult for EBRT to match the proven track record of BT seen over the past decade.

  19. KRAS and VEGF gene 3'-UTR single nucleotide polymorphisms predicted susceptibility in colorectal cancer

    PubMed Central

    Xing, Xiaorui; Li, Xin; Xia, Tian; Long, Hanan

    2017-01-01

    Single nucleotide polymorphisms (SNPs) in tumor-related genes have been reported to play important roles in cancer development. Recent studies have shown that 3’-untranslated regions (UTR) polymorphisms are associated with the occurrence and prognosis of cancers. The aim of this study is to analyze the association between KRAS and VEGF gene 3’-UTR SNPs and genetic susceptibility to colorectal cancer (CRC). In this case-control study of 371 CRC cases and 246 healthy controls, we analyzed the association between one SNP (rs1137188G > A) in the KRAS gene and four SNPs (rs3025039C > T, rs3025040C > T, rs3025053G > A and rs10434A > G) in the VEGF gene and CRC susceptibility by the improved multiplex ligase detection reaction (iMLDR) method. We checked the selected SNPs’ minor allele frequency and its distribution in the frequency of Chinese people by Hap-map database and Hardy-Weinberg equilibrium, and used multivariate logistic regression models to estimate adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs). We found that the rs3025039C variant genotype in the VEGF gene was associated with a significant protection for CRC (AOR = 0.693, 95% CI = 0.485–0.989; P = 0.043 for CC and CT+TT). Nevertheless, the difference was no longer significant after Bonferroni correction (Bonferroni-adjusted P = 0.172). In genetic polymorphisms analysis, we found that the KRAS rs1137188 variant AA genotype had higher portion of tumor size (≥ 5 cm) (P = 0.01; Bonferroni-adjusted P = 0.04), which suggested that the rs1137188 variant AA genotype may significantly be associated with increased progression of CRC. In conclusion, our study suggested that these five SNPs in the KRAS gene and the VEGF gene were not associated with CRC susceptibility in Han Chinese in Sichuan province. PMID:28328959

  20. Robotic single site versus robotic multiport hysterectomy in early endometrial cancer: a case control study

    PubMed Central

    2016-01-01

    Objective To compare surgical outcomes and cost of robotic single-site hysterectomy (RSSH) versus robotic multiport hysterectomy (RMPH) in early stage endometrial cancer. Methods This is a retrospective case-control study, comparing perioperative outcomes and costs of RSSH and RMPH in early stage endometrial cancer patients. RSSH were matched 1:2 according to age, body mass index, comorbidity, the International Federation of Gynecology and Obstetric (FIGO) stage, type of radical surgery, histologic type, and grading. Mean hospital cost per discharge was calculated summarizing the cost of daily hospital room charges, operating room, cost of supplies and length of hospital stay. Results A total of 23 women who underwent RSSH were matched with 46 historic controls treated by RMPH in the same institute, with the same surgical team. No significant differences were found in terms of age, histologic type, stage, and grading. Operative time was similar: 102.5 minutes in RMPH and 110 in RSSH (p=0.889). Blood loss was lower in RSSH than in RMPH (respectively, 50 mL vs. 100 mL, p=0.001). Hospital stay was 3 days in RMPH and 2 days in RSSH (p=0.001). No intraoperative complications occurred in both groups. Early postoperative complications were 2.2% in RMPH and 4.3% in RSSH. Overall cost was higher in RMPH than in RSSH (respectively, $7,772.15 vs. $5,181.06). Conclusion Our retrospective study suggests the safety and feasibility of RSSH for staging early endometrial cancer without major differences from the RMPH in terms of surgical outcomes, but with lower hospital costs. Certainly, further studies are eagerly warranted to confirm our findings. PMID:27171672

  1. Chronological changes in lung cancer surgery in a single Japanese institution

    PubMed Central

    Nakamura, Haruhiko; Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

    2017-01-01

    Background The aim of this study was to evaluate the chronological changes in epidemiological factors and surgical outcomes in patients with lung cancer who underwent surgery in a single Japanese institution. Patients and methods A clinicopathological database of patients with lung cancer who underwent surgery with curative intent from January 1974 to December 2014 was reviewed. The chronological changes in various factors, including patient’s age, sex, histological type, tumor size, pathological stage (p-stage), surgical method, operative time, intraoperative blood loss, 30-day mortality, and postoperative overall survival (OS), were evaluated. Results A total of 1,616 patients were included. The numbers of resected patients, females, adenocarcinomas, p-stage IA patients, and age at the time of surgery increased with time, but tumor size decreased (all P<0.0001). Concerning surgical methods, the number of sublobar resections increased, but that of pneumonectomies decreased (P<0.0001). The mean operative time, intraoperative blood loss, and the postoperative 30-day mortality rate decreased (all P<0.0001). When the patients were divided into two groups (1974–2004 and 2005–2014), the 5-year OS rates for all patients and for p-stage IA patients improved from 44% to 79% and from 73% to 89%, respectively (all P<0.0001). The best 5-year OS rate was obtained for sublobar resection (73%), followed by lobectomy (60%), combined resection (22%), and pneumonectomy (21%; P<0.0001). Conclusion Changes in epidemiological factors, a trend toward less invasive surgery, and a remarkably improved postoperative OS were confirmed, which demonstrated the increasingly important role of surgery in therapeutic strategies for lung cancer. PMID:28331339

  2. Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue

    PubMed Central

    Gerdes, Michael J.; Sevinsky, Christopher J.; Sood, Anup; Adak, Sudeshna; Bello, Musodiq O.; Bordwell, Alexander; Can, Ali; Corwin, Alex; Dinn, Sean; Filkins, Robert J.; Hollman, Denise; Kamath, Vidya; Kaanumalle, Sireesha; Kenny, Kevin; Larsen, Melinda; Lazare, Michael; Lowes, Christina; McCulloch, Colin C.; McDonough, Elizabeth; Pang, Zhengyu; Rittscher, Jens; Santamaria-Pang, Alberto; Sarachan, Brion D.; Seel, Maximilian L.; Seppo, Antti; Shaikh, Kashan; Sui, Yunxia; Zhang, Jingyu; Ginty, Fiona

    2013-01-01

    Limitations on the number of unique protein and DNA molecules that can be characterized microscopically in a single tissue specimen impede advances in understanding the biological basis of health and disease. Here we present a multiplexed fluorescence microscopy method (MxIF) for quantitative, single-cell, and subcellular characterization of multiple analytes in formalin-fixed paraffin-embedded tissue. Chemical inactivation of fluorescent dyes after each image acquisition round allows reuse of common dyes in iterative staining and imaging cycles. The mild inactivation chemistry is compatible with total and phosphoprotein detection, as well as DNA FISH. Accurate computational registration of sequential images is achieved by aligning nuclear counterstain-derived fiducial points. Individual cells, plasma membrane, cytoplasm, nucleus, tumor, and stromal regions are segmented to achieve cellular and subcellular quantification of multiplexed targets. In a comparison of pathologist scoring of diaminobenzidine staining of serial sections and automated MxIF scoring of a single section, human epidermal growth factor receptor 2, estrogen receptor, p53, and androgen receptor staining by diaminobenzidine and MxIF methods yielded similar results. Single-cell staining patterns of 61 protein antigens by MxIF in 747 colorectal cancer subjects reveals extensive tumor heterogeneity, and cluster analysis of divergent signaling through ERK1/2, S6 kinase 1, and 4E binding protein 1 provides insights into the spatial organization of mechanistic target of rapamycin and MAPK signal transduction. Our results suggest MxIF should be broadly applicable to problems in the fields of basic biological research, drug discovery and development, and clinical diagnostics. PMID:23818604

  3. Fulvestrant in advanced breast cancer following tamoxifen and aromatase inhibition: a single center experience.

    PubMed

    Wang, Jayson; Jain, Sandeep; Coombes, Charles R; Palmieri, Carlo

    2009-01-01

    Fulvestrant is a pure estrogen receptor (ER) antagonist with no agonist effects. We describe the experience of a single center involving 45 postmenopausal women with advanced breast cancer where fulvestrant was utilized following progression on tamoxifen and a third generation aromatase inhibitor. Patients received fulvestrant as first line one (2%), second line 18 (40%), third line 13 (29%), fourth line 10 (22%), and fifth line three (7%) treatment. Median duration of treatment with Fulvestrant was 4 months (range 1-20 months). One patient had a partial response, 14 other (31%) experienced clinical benefit (CB) (defined as response or stable disease for at least 6 months). The median time to progression (TTP) from initiation of fulvestrant was 4 months (range 1-20 months) and the median survival was 10 months (range 1-55 months). In those patients who experienced CB the median TTP was 10 months (range 6-20) and median survival was 21 months (range 7-55). Fulvestrant was well tolerated; two patients experienced side effects severe enough to stop therapy. Despite the fact that fulvestrant was used in the majority of cases, later in the treatment sequence CB was seen in a number of patients. This data suggest fulvestrant is well tolerated and is a useful treatment option in patients with advanced breast cancer who progress on prior endocrine treatment.

  4. Targeting single-walled carbon nanotubes for the treatment of breast cancer using photothermal therapy

    NASA Astrophysics Data System (ADS)

    Neves, Luís F. F.; Krais, John J.; Van Rite, Brent D.; Ramesh, Rajagopal; Resasco, Daniel E.; Harrison, Roger G.

    2013-09-01

    This paper focuses on the targeting of single-walled carbon nanotubes (SWNTs) for the treatment of breast cancer with minimal side effects using photothermal therapy. The human protein annexin V (AV) binds specifically to anionic phospholipids expressed externally on the surface of tumour cells and endothelial cells that line the tumour vasculature. A 2 h incubation of the SWNT-AV conjugate with proliferating endothelial cells followed by washing and near-infrared (NIR) irradiation at a wavelength of 980 nm was enough to induce significant cell death; there was no significant cell death with irradiation or the conjugate alone. Administration of the same conjugate i.v. in BALB/c female mice with implanted 4T1 murine mammary at a dose of 0.8 mg SWNT kg-1 and followed one day later by NIR irradiation of the tumour at a wavelength of 980 nm led to complete disappearance of implanted 4T1 mouse mammary tumours for the majority of the animals by 11 days since the irradiation. The combination of the photothermal therapy with the immunoadjuvant cyclophosphamide resulted in increased survival. The in vivo results suggest the SWNT-AV/NIR treatment is a promising approach to treat breast cancer.

  5. Micromagnetic Cancer Cell Immobilization and Release for Real-Time Single Cell Analysis

    NASA Astrophysics Data System (ADS)

    Jaiswal, Devina; Rad, Armin Tahmasbi; Nieh, Mu-Ping; Claffey, Kevin P.; Hoshino, Kazunori

    2017-04-01

    Understanding the interaction of live cells with macromolecules is crucial for designing efficient therapies. Considering the functional heterogeneity found in cancer cells, real-time single cell analysis is necessary to characterize responses. In this study, we have designed and fabricated a microfluidic channel with patterned micromagnets which can temporarily immobilize the cells during analysis and release them after measurements. The microchannel is composed of plain coverslip top and bottom panels to facilitate easy microscopic observation and undisturbed application of analytes to the cells. Cells labeled with functionalized magnetic beads were immobilized in the device with an efficiency of 90.8±3.6%. Since the micromagnets are made of soft magnetic material (Ni), they released cells when external magnetic field was turned off from the channel. This allows the reuse of the channel for a new sample. As a model drug analysis, the immobilized breast cancer cells (MCF7) were exposed to fluorescent lipid nanoparticles and association and dissociation were measured through fluorescence analysis. Two concentrations of nanoparticles, 0.06 μg/ml and 0.08 μg/ml were tested and time lapse images were recorded and analyzed. The microfluidic device was able to provide a microenvironment for sample analysis, making it an efficient platform for real-time analysis.

  6. Relationship Between Cytokine Gene Single Nucleotide Polymorphisms and Symptom Burden and Quality of Life in Lung Cancer Survivors

    PubMed Central

    Rausch, Sarah M.; Clark, Matthew M.; Patten, Christi; Liu, Heshan; Felten, Sara; Li, Yafei; Sloan, Jeff; Yang, Ping

    2011-01-01

    BACKGROUND Previous research has demonstrated that many lung cancer survivors report difficulties with symptom control and experience a poor quality of life (QOL). Although recent studies have suggested a relationship of single nucleotide polymorphisms (SNPs) in several cytokine genes with cancer susceptibility and prognosis, associations with symptom burden and QOL have not been examined. The current study was conducted to identify SNPs related to symptom burden and QOL outcomes in lung cancer survivors. METHODS All participants were enrolled in the Mayo Clinic Lung Cancer Cohort following diagnosis of lung cancer. A total of 1149 Caucasian lung cancer survivors completed questionnaires and had genetic samples available. The main outcome measures were symptom burden as measured by the Lung Cancer Symptom Scale and health-related QOL as measured by the Short-Form General Health Survey. RESULTS Twenty-one SNPs in cytokine genes were associated with symptom burden and QOL outcomes. Our results suggested both specificity and consistency of cytokine gene SNPs in predicting outcomes. CONCLUSIONS These results provide support for genetic predisposition to QOL and symptom burden and may aid in identification of lung cancer survivors at high risk for symptom management and QOL difficulties. PMID:20564140

  7. Breast cancer margin detection with a single frequency terahertz imaging system

    NASA Astrophysics Data System (ADS)

    Yngvesson, Sigfrid K.; Karellas, Andrew; Glick, Stephen; Khan, Ashraf; Siqueira, Paul R.; Kelly, Patrick A.; St. Peter, Benjamin

    2016-03-01

    The ability to discern malignant from benign tissue in excised human breast specimens in Breast Conservation Surgery (BCS) was evaluated using a prototype single frequency terahertz radiation. Terahertz (THz) images of the specimens in reflection mode were obtained by employing a gas laser source and mechanical scanning. The images were correlated with optical histological micrographs of the same specimens, and a mean discrimination of 73% was found for five out of six samples using Receiver Operating Characteristic (ROC) analysis. This result is similar to what has previously been obtained using Terahertz pulsed imaging (TPI) techniques. We will discuss the specific advantages of Single frequency THz imaging (SFTI) compared with TPI for potentially allowing the development of much faster, more compact and less expensive cancer imaging systems that could be adapted for employment in the operating room. The system design and characterization of the prototype SFTI system are discussed in detail. The initial results are encouraging but further development of the technology and clinical evaluation is needed to evaluate its feasibility in the clinical environment.

  8. The cardiotoxicity of cetuximab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer patients

    PubMed Central

    Tang, Xue-Miao; Chen, Hao; Liu, Yu; Huang, Bin-Lian; Zhang, Xiu-Quan; Yuan, Jian-Mei; He, Xia

    2017-01-01

    Abstract The cardiac safety of cetuximab, particularly as single approach, has not been investigated extensively. This trial was designed to evaluate the cardiac safety of cetuximab as salvage monotherapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Cetuximab was administrated at an initial dose of 400 mg/m2on day 1 (week 1), followed by a maintenance dose of 250 mg/m2 on day 1 of each 7-day cycle. Electrocardiograph (ECG), routine laboratory tests, and troponin I (TNI) Ultra were performed at baseline, during, and after the cetuximab therapy. The incidence of abnormal ECGs, elevated TNI Ultra, cardiac events, and noncardiac events were recorded and analyzed. TNI Ultra+ was found in 20 patients (32.3%) during the cetuximab therapy.TNI Ultra+ occurred more frequently in patients with more than 3 organs affected and accepted fourth or above lines of chemotherapy. The most frequent abnormal ECG was ST depression in 24 (38.7%) patients. The elevated TNI Ultra and abnormal ECGs could recover after the cetuximab therapy. The most of cardiac adverse events were mild and transient and the noncardiac adverse events were also consistent with the known safety profile for cetuximab. Cetuximab showed its cardiac safety as a single agent for chemotherapy-refractory mCRC patients. And TNI Ultra and ECG could be sensitive and convenient approaches for the surveillance of adverse events. PMID:28099361

  9. Impact of genetic dynamics and single-cell heterogeneity on development of nonstandard personalized medicine strategies for cancer

    PubMed Central

    Beckman, Robert A.; Schemmann, Gunter S.; Yeang, Chen-Hsiang

    2012-01-01

    Cancers are heterogeneous and genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type. However, it does not yet systematically address heterogeneity at the single-cell level within a single individual’s cancer or the dynamic nature of cancer due to genetic and epigenetic change as well as transient functional changes. We have developed a mathematical model of personalized cancer therapy incorporating genetic evolutionary dynamics and single-cell heterogeneity, and have examined simulated clinical outcomes. Analyses of an illustrative case and a virtual clinical trial of over 3 million evaluable “patients” demonstrate that augmented (and sometimes counterintuitive) nonstandard personalized medicine strategies may lead to superior patient outcomes compared with the current personalized medicine approach. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression, generally focusing on the average, static, and current properties of the sample. Nonstandard strategies also consider minor subclones, dynamics, and predicted future tumor states. Our methods allow systematic study and evaluation of nonstandard personalized medicine strategies. These findings may, in turn, suggest global adjustments and enhancements to translational oncology research paradigms. PMID:22891318

  10. Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

    PubMed Central

    Bailey, Swneke D.; Desai, Kinjal; Kron, Ken J.; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A.; Treloar, Aislinn E.; Dowar, Mark; Thu, Kelsie L.; Cescon, David W.; Silvester, Jennifer; Yang, S. Y. Cindy; Wu, Xue; Pezo, Rossanna C.; Haibe-Kains, Benjamin; Mak, Tak W.; Bedard, Philippe L.; Pugh, Trevor J.; Sallari, Richard C.; Lupien, Mathieu

    2016-01-01

    Sustained expression of the oestrogen receptor alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon oestrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers2–5, implying that other mechanisms underlie the persistent expression of ESR1. We report the significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by a functional inherited single nucleotide variant (SNV) rs9383590 that accounts for several breast cancer risk-loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. PMID:27571262

  11. Association Between Single Nucleotide Polymorphism +276G > T (rs1501299) in ADIPOQ and Endometrial Cancer.

    PubMed

    Bieńkiewicz, Jan; Smolarz, Beata; Malinowski, Andrzej

    2016-01-01

    Current literature gives evidence of an indisputable role adiponectin plays in adipose tissue metabolism and obesity-related diseases. Moreover, latest research efforts focus on linking genetic markers of this adipocytokine's gene (ADIPOQ) with cancer. Aim of this study was to determine the genotype distribution of single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQ and an attempt to identify the impact this polymorphism exerts on endometrial cancer risk in obese females. The test group comprised 90 women treated surgically for endometrial cancer between 2000 and 2012 in the Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Polish Mothers' Memorial Hospital - Research Institute, Lodz, Poland. 90 individuals treated in the parallel period for uterine fibroids constituted the control group. Patients within both groups were stratified according to BMI into: lean, overweight and obese subjects. Statistical analysis was performed between two major groups and, furthermore, within the abovementioned subgroups. The analysis revealed that allele G of the investigated polymorphism in obese women with endometrial cancer is significantly more frequent, and allele T is significantly less frequent than in lean controls. However, no significant correlation was observed between the polymorphism and endometrial cancer in lean and overweight females. Single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQ may be considered to be a risk factor of endometrial cancer. Further research on SNP in EC is warranted to obtain more conclusive outcomes.

  12. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer

    PubMed Central

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-01-01

    Abstract The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC). A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0). Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78–0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72–0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27–1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups. In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  13. Evaluation of a Single-Isocenter Technique for Axillary Radiotherapy in Breast Cancer

    SciTech Connect

    Beek, Suzanne van Jaeger, Katrien de; Mijnheer, Ben |; Vliet-Vroegindeweij, Corine van

    2008-10-01

    The aim of this study was to develop a technique for axillary radiotherapy that minimizes the risk of radiation-induced damage to the surrounding normal tissue (i.e., arm, shoulder, lung, esophagus, and spinal cord) while keeping the risk of a nodal recurrence to a minimum. A planning study was performed in 20 breast cancer patients. The target volume of the axillary treatment encompassed the periclavicular and axillary lymph node areas. The 3-dimensional (3D) computed tomography (CT) information in this study was used to outline the lymph node areas and the organs at risk (i.e., the esophagus, spinal cord, brachial plexus, and lung). A conventional AP-PA technique (with a transmission plate placed in the AP beam) was evaluated. In addition, a new single-isocenter technique consisting of AP/PA fields using a gantry rotation of {+-}20 deg. and a medial AP segment was developed. Both techniques were compared by evaluation of the calculated dose distributions and the dose-volume histograms of the target volume and surrounding organs at risk. The field borders and humeral shielding were redefined based on the 3D anatomical references. Adapting the humeral shielding reduced the irradiated volume by 19% and might contribute to a reduction of the incidence of arm edema and impairment of shoulder function. The maximum radiation dose in the esophagus and spinal cord was reduced by more than 50% using the single-isocenter technique. The difference between both techniques with respect to the mean doses in the target volume and lung, and the maximum dose in brachial plexus, was not statistically significant. Moreover, the single-isocenter technique allowed a fast and easy treatment preparation and reduced the execution time considerably (with approximately 10 minutes per fraction)

  14. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

    PubMed

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-06-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

  15. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

    PubMed Central

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-01-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life. PMID:26038960

  16. Relevance of randomised controlled trials in oncology.

    PubMed

    Tannock, Ian F; Amir, Eitan; Booth, Christopher M; Niraula, Saroj; Ocana, Alberto; Seruga, Bostjan; Templeton, Arnoud J; Vera-Badillo, Francisco

    2016-12-01

    Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing.

  17. Strategies to improve retention in randomised trials

    PubMed Central

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-01-01

    questionnaire question order either increased or decreased trial questionnaire response/retention. There was also no evidence that a telephone survey was either more or less effective than a monetary incentive and a questionnaire. As our analyses are based on single trials, the effect on questionnaire response of using offers of charity donations, sending reminders to trial sites and when a questionnaire is sent, may need further evaluation. Case management and behavioural strategies used for trial retention may also warrant further evaluation. Authors' conclusions Most of the retention trials that we identified evaluated questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. Monetary incentives and offers of monetary incentives increased postal and electronic questionnaire response. Some other strategies evaluated in single trials looked promising but need further evaluation. Application of the findings of this review would depend on trial setting, population, disease area, data collection and follow-up procedures. PLAIN LANGUAGE SUMMARY Methods that might help to keep people in randomised trials Background Most trials follow people up to collect data through personal contact after they have been recruited. Some trials get data from other sources, such as routine collected data or disease registers. There are many ways to collect data from people in trials, and these include using letters, the internet, telephone calls, text messaging, face-to-face meetings or the return of medical test kits. Most trials have missing data, for example, because people are too busy to reply, are unable to attend a clinic, have moved or no longer want to participate. Sometimes data has not been recorded at study sites, or are not sent to the trial co-ordinating centre. Researchers call this 'loss to follow-up', 'drop out' or 'attrition' and it can affect the trial's results. For example, if the people with the most or least

  18. Highly sensitive, non-invasive detection of colorectal cancer mutations using single molecule, third generation sequencing

    PubMed Central

    Russo, Giancarlo; Patrignani, Andrea; Poveda, Lucy; Hoehn, Frederic; Scholtka, Bettina; Schlapbach, Ralph; Garvin, Alex M.

    2015-01-01

    Colorectal cancer (CRC) represents one of the most prevalent and lethal malignant neoplasms and every individual of age 50 and above should undergo regular CRC screening. Currently, the most effective preventive screening procedure to detect adenomatous polyps, the precursors to CRC, is colonoscopy. Since every colorectal cancer starts as a polyp, detecting all polyps and removing them is crucial. By exactly doing that, colonoscopy reduces CRC incidence by 80%, however it is an invasive procedure that might have unpleasant and, in rare occasions, dangerous side effects. Despite numerous efforts over the past two decades, a non-invasive screening method for the general population with detection rates for adenomas and CRC similar to that of colonoscopy has not yet been established. Recent advances in next generation sequencing technologies have yet to be successfully applied to this problem, because the detection of rare mutations has been hindered by the systematic biases due to sequencing context and the base calling quality of NGS. We present the first study that applies the high read accuracy and depth of single molecule, real time, circular consensus sequencing (SMRT-CCS) to the detection of mutations in stool DNA in order to provide a non-invasive, sensitive and accurate test for CRC. In stool DNA isolated from patients diagnosed with adenocarcinoma, we are able to detect mutations at frequencies below 0.5% with no false positives. This approach establishes a foundation for a non-invasive, highly sensitive assay to screen the population for CRC and the early stage adenomas that lead to CRC. PMID:27054083

  19. Highly sensitive, non-invasive detection of colorectal cancer mutations using single molecule, third generation sequencing.

    PubMed

    Russo, Giancarlo; Patrignani, Andrea; Poveda, Lucy; Hoehn, Frederic; Scholtka, Bettina; Schlapbach, Ralph; Garvin, Alex M

    2015-12-01

    Colorectal cancer (CRC) represents one of the most prevalent and lethal malignant neoplasms and every individual of age 50 and above should undergo regular CRC screening. Currently, the most effective preventive screening procedure to detect adenomatous polyps, the precursors to CRC, is colonoscopy. Since every colorectal cancer starts as a polyp, detecting all polyps and removing them is crucial. By exactly doing that, colonoscopy reduces CRC incidence by 80%, however it is an invasive procedure that might have unpleasant and, in rare occasions, dangerous side effects. Despite numerous efforts over the past two decades, a non-invasive screening method for the general population with detection rates for adenomas and CRC similar to that of colonoscopy has not yet been established. Recent advances in next generation sequencing technologies have yet to be successfully applied to this problem, because the detection of rare mutations has been hindered by the systematic biases due to sequencing context and the base calling quality of NGS. We present the first study that applies the high read accuracy and depth of single molecule, real time, circular consensus sequencing (SMRT-CCS) to the detection of mutations in stool DNA in order to provide a non-invasive, sensitive and accurate test for CRC. In stool DNA isolated from patients diagnosed with adenocarcinoma, we are able to detect mutations at frequencies below 0.5% with no false positives. This approach establishes a foundation for a non-invasive, highly sensitive assay to screen the population for CRC and the early stage adenomas that lead to CRC.

  20. Report: Evaluation on diagnosis significance of single high frequency Ultrasonography and mammography and combination on Breast Cancer.

    PubMed

    Sun, Huifang; Wang, Bo; Ding, Changmao; Yu, Zhan; Gao, Jianbo

    2016-07-01

    To evaluate the diagnosis significance of single high-frequency ultrasonography and mammography and combination therapy of both on breast cancer. 352 cases of female breast cancer patients were selected from The First Affiliated Hospital of Zhengzhou University from January 2012 to December 2014. Among the 352 patients, 124 patients had only performed high-frequency ultrasonography detection, 102 cases of patients were only conducted mammography, and 126 patients had applied the combination detection of high-frequency ultrasonography and mammography. The coincidence rate of single mammography detection was 79.4%, the misdiagnosis rate was 10.8%, and the missed diagnosis rate was 9.8%; the coincidence rate of single high frequency ultrasonography detection was 83.9%, the misdiagnosis rate was 11.5%, the missed diagnosis rate was 4.6%; the coincidence rate of combination of high frequency ultrasonography detection was 89.7%, the misdiagnosis rate was 6.3%, the missed diagnosis rate was 4.0%. The detection rate and missed diagnosis rate of combination diagnosis had statistical difference with single high frequency ultrasonography and single mammography. There was no statistical difference on misdiagnosis rate. mammography and high frequency ultrasonography respectively had their own advantages. The combination application of both had better diagnosis complementary, and could significantly improved the detection rate and accuracy rate on breast cancer, and decreased the misdiagnosis rate and missed diagnosis rate.

  1. Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence; Chang, Stephanie; Kuo, Timothy; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Greco, Ralph; Yang, George P.; Koong, Albert C.

    2008-11-01

    Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

  2. Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Willis, Scooter; Villalobos, Victor M.; Gevaert, Olivier; Abramovitz, Mark; Williams, Casey; Sikic, Branimir I.; Leyland-Jones, Brian

    2016-01-01

    Purpose To discover novel prognostic biomarkers in ovarian serous carcinomas. Methods A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer’s method and selected for statistical significance with a false discovery rate (FDR) <.05 using the Benjamini-Hochberg method. Results Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82). Conclusion A meta-analysis of all single genes identified thirty-two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi-gene signature and tested in future ovarian cohorts. PMID:26886260

  3. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

    PubMed Central

    Campa, Daniele; Pastore, Manuela; Gentiluomo, Manuel; Talar-Wojnarowska, Renata; Kupcinskas, Juozas; Malecka-Panas, Ewa; Neoptolemos, John P.; Niesen, Willem; Vodicka, Pavel; Fave, Gianfranco Delle; Bueno-de-Mesquita, H. Bas; Gazouli, Maria; Pacetti, Paola; Di Leo, Milena; Ito, Hidemi; Klüter, Harald; Soucek, Pavel; Corbo, Vincenzo; Yamao, Kenji; Hosono, Satoyo; Kaaks, Rudolf; Vashist, Yogesh; Gioffreda, Domenica; Strobel, Oliver; Shimizu, Yasuhiro; Dijk, Frederike; Andriulli, Angelo; Ivanauskas, Audrius; Bugert, Peter; Tavano, Francesca; Vodickova, Ludmila; Zambon, Carlo Federico; Lovecek, Martin; Landi, Stefano; Key, Timothy J.; Boggi, Ugo; Pezzilli, Raffaele; Jamroziak, Krzysztof; Mohelnikova-Duchonova, Beatrice; Mambrini, Andrea; Bambi, Franco; Busch, Olivier; Pazienza, Valerio; Valente, Roberto; Theodoropoulos, George E.; Hackert, Thilo; Capurso, Gabriele; Cavestro, Giulia Martina; Pasquali, Claudio; Basso, Daniela; Sperti, Cosimo; Matsuo, Keitaro; Büchler, Markus; Khaw, Kay-Tee; Izbicki, Jakob; Costello, Eithne; Katzke, Verena; Michalski, Christoph; Stepien, Anna; Rizzato, Cosmeri; Canzian, Federico

    2016-01-01

    The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk. PMID:27486979

  4. Quantitative Analysis of Single Amino Acid Variant Peptides Associated with Pancreatic Cancer in Serum by an Isobaric Labeling Quantitative Method

    PubMed Central

    2015-01-01

    Single amino acid variations are highly associated with many human diseases. The direct detection of peptides containing single amino acid variants (SAAVs) derived from nonsynonymous single nucleotide polymorphisms (SNPs) in serum can provide unique opportunities for SAAV associated biomarker discovery. In the present study, an isobaric labeling quantitative strategy was applied to identify and quantify variant peptides in serum samples of pancreatic cancer patients and other benign controls. The largest number of SAAV peptides to date in serum including 96 unique variant peptides were quantified in this quantitative analysis, of which five variant peptides showed a statistically significant difference between pancreatic cancer and other controls (p-value < 0.05). Significant differences in the variant peptide SDNCEDTPEAGYFAVAVVK from serotransferrin were detected between pancreatic cancer and controls, which was further validated by selected reaction monitoring (SRM) analysis. The novel biomarker panel obtained by combining α-1-antichymotrypsin (AACT), Thrombospondin-1 (THBS1) and this variant peptide showed an excellent diagnostic performance in discriminating pancreatic cancer from healthy controls (AUC = 0.98) and chronic pancreatitis (AUC = 0.90). These results suggest that large-scale analysis of SAAV peptides in serum may provide a new direction for biomarker discovery research. PMID:25393578

  5. High-Content Analysis of Breast Cancer Using Single-Cell Deep Transfer Learning.

    PubMed

    Kandaswamy, Chetak; Silva, Luís M; Alexandre, Luís A; Santos, Jorge M

    2016-03-01

    High-content analysis has revolutionized cancer drug discovery by identifying substances that alter the phenotype of a cell, which prevents tumor growth and metastasis. The high-resolution biofluorescence images from assays allow precise quantitative measures enabling the distinction of small molecules of a host cell from a tumor. In this work, we are particularly interested in the application of deep neural networks (DNNs), a cutting-edge machine learning method, to the classification of compounds in chemical mechanisms of action (MOAs). Compound classification has been performed using image-based profiling methods sometimes combined with feature reduction methods such as principal component analysis or factor analysis. In this article, we map the input features of each cell to a particular MOA class without using any treatment-level profiles or feature reduction methods. To the best of our knowledge, this is the first application of DNN in this domain, leveraging single-cell information. Furthermore, we use deep transfer learning (DTL) to alleviate the intensive and computational demanding effort of searching the huge parameter's space of a DNN. Results show that using this approach, we obtain a 30% speedup and a 2% accuracy improvement.

  6. Superresolution Imaging of Clinical Formalin Fixed Paraffin Embedded Breast Cancer with Single Molecule Localization Microscopy

    PubMed Central

    Creech, Matthew K.; Wang, Jing; Nan, Xiaolin; Gibbs, Summer L.

    2017-01-01

    Millions of archived formalin-fixed, paraffin-embedded (FFPE) specimens contain valuable molecular insight into healthy and diseased states persevered in their native ultrastructure. To diagnose and treat diseases in tissue on the nanoscopic scale, pathology traditionally employs electron microscopy (EM), but this platform has significant limitations including cost and painstaking sample preparation. The invention of single molecule localization microscopy (SMLM) optically overcame the diffraction limit of light to resolve fluorescently labeled molecules on the nanoscale, leading to many exciting biological discoveries. However, applications of SMLM in preserved tissues has been limited. Through adaptation of the immunofluorescence workflow on FFPE sections milled at histological thickness, cellular architecture can now be visualized on the nanoscale using SMLM including individual mitochondria, undulations in the nuclear lamina, and the HER2 receptor on membrane protrusions in human breast cancer specimens. Using astigmatism imaging, these structures can also be resolved in three dimensions to a depth of ~800 nm. These results demonstrate the utility of SMLM in efficiently uncovering ultrastructural information of archived clinical samples, which may offer molecular insights into the physiopathology of tissues to assist in disease diagnosis and treatment using conventional sample preparation methods. PMID:28098202

  7. Trastuzumab for the treatment of HER2-positive metastatic gastric cancer : a NICE single technology appraisal.

    PubMed

    Spackman, Eldon; Rice, Stephen; Norman, Gill; Suh, Dong-Churl; Eastwood, Alison; Palmer, Stephen

    2013-03-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of trastuzumab, Roche Pharmaceuticals, to submit evidence for the clinical and cost effectiveness of this drug for the treatment of advanced gastric cancer (aGC), as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the evidence review group (ERG). This article provides a description of the company submission, the ERG report and NICE's subsequent decisions. In the initial appraisal by NICE, trastuzumab was rejected for use in the licensed population. Given this result, the manufacturer submitted additional evidence. In the final appraisal decision, trastuzumab was approved, in accordance with supplementary guidance issued by NICE on appraising life-extending, end-of-life treatments, for patients whose human epidermal growth factor receptor 2 (HER2) status was defined by an immunohistochemistry 3 positive (IHC3+) result. This appraisal highlights the need to fully assess the impact of different approaches to diagnostic testing on the cost effectiveness of targeted treatments. In this appraisal, it was found that the diagnostic strategy influenced the effectiveness and cost of trastuzumab. In the future, different diagnostic strategies should be compared in the incremental cost-effectiveness analysis.

  8. Superresolution Imaging of Clinical Formalin Fixed Paraffin Embedded Breast Cancer with Single Molecule Localization Microscopy.

    PubMed

    Creech, Matthew K; Wang, Jing; Nan, Xiaolin; Gibbs, Summer L

    2017-01-18

    Millions of archived formalin-fixed, paraffin-embedded (FFPE) specimens contain valuable molecular insight into healthy and diseased states persevered in their native ultrastructure. To diagnose and treat diseases in tissue on the nanoscopic scale, pathology traditionally employs electron microscopy (EM), but this platform has significant limitations including cost and painstaking sample preparation. The invention of single molecule localization microscopy (SMLM) optically overcame the diffraction limit of light to resolve fluorescently labeled molecules on the nanoscale, leading to many exciting biological discoveries. However, applications of SMLM in preserved tissues has been limited. Through adaptation of the immunofluorescence workflow on FFPE sections milled at histological thickness, cellular architecture can now be visualized on the nanoscale using SMLM including individual mitochondria, undulations in the nuclear lamina, and the HER2 receptor on membrane protrusions in human breast cancer specimens. Using astigmatism imaging, these structures can also be resolved in three dimensions to a depth of ~800 nm. These results demonstrate the utility of SMLM in efficiently uncovering ultrastructural information of archived clinical samples, which may offer molecular insights into the physiopathology of tissues to assist in disease diagnosis and treatment using conventional sample preparation methods.

  9. Single-walled and multi-walled carbon nanotubes based drug delivery system: Cancer therapy: A review.

    PubMed

    Dineshkumar, B; Krishnakumar, K; Bhatt, A R; Paul, D; Cherian, J; John, A; Suresh, S

    2015-01-01

    Carbon nanotubes (CNTs) are advanced nano-carrier for delivery of drugs especially anti-cancer drugs. In the field of CNT-based drug delivery system, both single-walled carbon nanotubes (SWCNTs) and multi-walled nanotubes (MWCNTs) can be used for targeting anticancer drugs in tissues and organs, where the high therapeutic effect is necessary. Benefits of the carbon nanotubes (CNTs) in drug delivery systems are; avoiding solvent usage and reducing the side effects. Therefore, the present review article described about achievement of SWCNTs and MWCNTs to deliver the anticancer drugs with different cancerous cell lines.

  10. Protocol for the CONVERT trial—Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status

    PubMed Central

    Falk, Sally; Ashcroft, Linda; Bewley, Michelle; Lorigan, Paul; Wilson, Elena; Groom, Nicki; Snee, Michael; Fournel, Pierre; Cardenal, Felipe; Bezjak, Andrea; Blackhall, Fiona

    2016-01-01

    Introduction Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small cell lung cancer (LS-SCLC). Following on from the Turrisi trial of once-daily versus twice-daily (BD) concurrent chemoradiotherapy, there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose. This trial has the potential to define a new standard chemo-RT regimen for patients with LS-SCLC and good performance status. Methods and analysis 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013. Patients were randomised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks) both starting on day 22 of cycle 1. Patients are followed up until death. The primary end point of the study is overall survival and secondary end points include local progression-free survival, metastasis-free survival, acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0, chemotherapy and RTdose intensity. Ethics and dissemination The trial received ethical approval from NRES Committee North West—Greater Manchester Central (07/H1008/229). There is a trial steering committee, including independent members and an independent data monitoring committee. Results will be published in a peer-reviewed journal and presented at international conferences. Trial registration number ISRCTN91927162; Pre-results. PMID:26792218

  11. Effective combination treatment of lung cancer cells by single vehicular delivery of siRNA and different anticancer drugs.

    PubMed

    Li, Jinming; Wang, Yuanyuan; Xue, Shanshan; Sun, Jinghua; Zhang, Wei; Hu, Ping; Ji, Liangnian; Mao, Zongwan

    In recent years, lung cancer has become one of the fastest growing cancers in the world. Thus, the development of efficient combination therapy to treat lung cancer has attracted significant attention in the cancer therapy field. In this article, we developed a single vehicle drug delivery system, based on quantum dot (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and different anticancer drugs (carboplatin, paclitaxel, and doxorubicin) simultaneously for treating A549 lung cancer cells efficiently by combination therapy. The QD nanoparticles were conjugated with l-arginine (l-Arg) and different kinds of hydroxypropyl-cyclodextrins (HP-α-CDs, HP-β-CDs, and HP-γ-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers). They were able to not only bind and transport the siRNA through electrostatic interactions with l-Arg residues but also accommodate various disparate anticancer drugs using different HP-CD modifications. Compared with free drug treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different anticancer drugs simultaneously exerted a threefold to fourfold increase in cytotoxicity in A549 cells, which greatly improved the treatment efficacy through combined action. Furthermore, the QD nanocarriers could be used as a probe for real-time imaging of the drug delivery and release because of their strong fluorescence properties. These findings indicate that multifunctional QD nanocarriers hold great promise as a powerful tool for combination therapy for lung cancer.

  12. Imaging and Intracellular Tracking of Cancer-Derived Exosomes Using Single-Molecule Localization-Based Super-Resolution Microscope.

    PubMed

    Chen, Chen; Zong, Shenfei; Wang, Zhuyuan; Lu, Ju; Zhu, Dan; Zhang, Yizhi; Cui, Yiping

    2016-10-05

    Exosomes are small membrane vesicles secreted by cells and enriched with plenty of proteins. Considering their significant roles in different physical activities and potential value for diagnostic drug delivery, researchers have put great efforts in in vitro tracking and content analysis of exosomes. Recently, the emergence of different kinds of super-resolution microscopy provides powerful tools for exosome study. Here, we demonstrate the application of single-molecule localization based super-resolution imaging technique in the imaging and tracking of cancer-derived exosomes. In the experiment, first, cancer-derived exosomes are extracted from the culture media of tumor cells. Then the exosome membrane receptors are labeled with photoswitchable probes, which allow super-resolution imaging of these membrane receptors via photoactivated localization microscopy (PALM) or stochastic optical reconstruction microscopy (STORM). By using human breast cancer cell-derived exosomes, we demonstrated simultaneous dual-color PALM/STORM imaging of two kinds of membrane receptors on the exosome membrane. Moreover, the successful labeling and imaging of exosomes make it possible to observe the interaction between cancer-derived exosomes and normal cells. Meanwhile, we realized the colocalization of cancer-derived exosomes and lysosomes in recipient cells with PALM/STORM imaging. Since exosomes play a vital role in intercellular communications, we anticipate that the presented PALM/STORM-based imaging and tracking of exosomes holds a great potential in the investigation of the mechanism of exosome-mediated cancer metastasis.

  13. Effective combination treatment of lung cancer cells by single vehicular delivery of siRNA and different anticancer drugs

    PubMed Central

    Li, Jinming; Wang, Yuanyuan; Xue, Shanshan; Sun, Jinghua; Zhang, Wei; Hu, Ping; Ji, Liangnian; Mao, Zongwan

    2016-01-01

    In recent years, lung cancer has become one of the fastest growing cancers in the world. Thus, the development of efficient combination therapy to treat lung cancer has attracted significant attention in the cancer therapy field. In this article, we developed a single vehicle drug delivery system, based on quantum dot (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and different anticancer drugs (carboplatin, paclitaxel, and doxorubicin) simultaneously for treating A549 lung cancer cells efficiently by combination therapy. The QD nanoparticles were conjugated with l-arginine (l-Arg) and different kinds of hydroxypropyl-cyclodextrins (HP-α-CDs, HP-β-CDs, and HP-γ-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers). They were able to not only bind and transport the siRNA through electrostatic interactions with l-Arg residues but also accommodate various disparate anticancer drugs using different HP-CD modifications. Compared with free drug treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different anticancer drugs simultaneously exerted a threefold to fourfold increase in cytotoxicity in A549 cells, which greatly improved the treatment efficacy through combined action. Furthermore, the QD nanocarriers could be used as a probe for real-time imaging of the drug delivery and release because of their strong fluorescence properties. These findings indicate that multifunctional QD nanocarriers hold great promise as a powerful tool for combination therapy for lung cancer. PMID:27695321

  14. mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer.

    PubMed

    Cann, Gordon M; Gulzar, Zulfiqar G; Cooper, Samantha; Li, Robin; Luo, Shujun; Tat, Mai; Stuart, Sarah; Schroth, Gary; Srinivas, Sandhya; Ronaghi, Mostafa; Brooks, James D; Talasaz, Amirali H

    2012-01-01

    Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and enumeration of CTCs is currently used as a prognostic indicator of survival in metastatic prostate cancer patients. Some evidence suggests that it is possible to derive additional information about tumors from expression analysis of CTCs, but the technical difficulty of isolating and analyzing individual CTCs has limited progress in this area. To assess the ability of a new generation of MagSweeper to isolate intact CTCs for downstream analysis, we performed mRNA-Seq on single CTCs isolated from the blood of patients with metastatic prostate cancer and on single prostate cancer cell line LNCaP cells spiked into the blood of healthy donors. We found that the MagSweeper effectively isolated CTCs with a capture efficiency that matched the CellSearch platform. However, unlike CellSearch, the MagSweeper facilitates isolation of individual live CTCs without contaminating leukocytes. Importantly, mRNA-Seq analysis showed that the MagSweeper isolation process did not have a discernible impact on the transcriptional profile of single LNCaPs isolated from spiked human blood, suggesting that any perturbations caused by the MagSweeper process on the transcriptional signature of isolated cells are modest. Although the RNA from patient CTCs showed signs of significant degradation, consistent with reports of short half-lives and apoptosis amongst CTCs, transcriptional signatures of prostate tissue and of cancer were readily detectable with single CTC mRNA-Seq. These results demonstrate that the MagSweeper provides access to intact CTCs and that these CTCs can potentially supply clinically relevant information.

  15. Colon cancer modulation by a diabetic environment: A single institutional experience

    PubMed Central

    Gonzalez, Nieves; Portal-Nuñez, Sergio; Zazo, Sandra; Corton, Marta; Minguez, Pablo; Gomez-Guerrero, Carmen; Arce, Jose Miguel; Sanz, Ana Belen; Mas, Sebastian; Aguilera, Oscar; Alvarez-Llamas, Gloria; Esbrit, Pedro; Ortiz, Alberto; Ayuso, Carmen; Egido, Jesus; Rojo, Federico; Garcia-Foncillas, Jesus

    2017-01-01

    Background Multiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior. Aim To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. Material and methods Retrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81 diabetic patients diagnosed of colon cancer matched with 79 non-diabetic colon cancer patients. The impact of streptozotocin-induced diabetes on the growth of colon cancer xenografts was studied in mice. Results The incidence of DM in 1,137 patients with colorectal cancer was 16%. The diabetic colon cancer cases and non-diabetic colon cancer controls were well matched for demographic and clinical variables. The ECOG Scale Performance Status was higher (worse) in diabetics (ECOG ≥1, 29.1% of controls vs 46.9% of diabetics, p = 0.02), but no significant differences were observed in tumor grade, adjuvant therapy, tumor site, lymphovascular invasion, stage, recurrence, death or cancer-related death. Moreover, no differences in tumor variables were observed between patients treated or not with metformin. In the xenograft model, tumor growth and histopathological characteristics did not differ between diabetic and nondiabetic animals. Conclusion Our findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed. PMID:28253286

  16. Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population

    PubMed Central

    Chang, Shen-Chih; Chang, Po-Yin; Butler, Brendan; Goldstein, Binh Y.; Mu, Lina; Cai, Lin; You, Nai-Chieh Y.; Baecker, Aileen; Yu, Shun-Zhang; Heber, David; Lu, Qing-Yi; Li, Liming; Greenland, Sander; Zhang, Zuo-Feng

    2014-01-01

    One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the

  17. Writing to patients: a randomised controlled trial.

    PubMed

    O'Reilly, Máire; Cahill, Mary R; Perry, Ivan J

    2006-01-01

    It has been suggested that consultants should consider writing directly to patients with a summary of their outpatient consultation. In a controlled trial involving consecutive new referrals to a haematology outpatient clinic, we randomised patients to receive either a personal letter from their consultant summarising their consultation (n = 77) or a brief note thanking them for attending the clinic (n = 73). Patients were assessed for recall of and satisfaction with the consultation by a single independent observer, using standardised methods. At the second visit to outpatients, the patients' median percentage recall of items discussed during the consultation was 67% (IQ range 50-80%) in the intervention group, versus 57% (IQ range 43-76%) in the control group (p = 0.3). Strongly positive views on the personal letter were expressed by patients and referring clinicians. The findings suggest that although personal letters do not substantially improve recall of the clinical encounter, they are feasible, highly valued by patients and acceptable to referring clinicians.

  18. Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case–control study in Japanese women

    PubMed Central

    2013-01-01

    Background Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. Methods A case–control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. Results High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR = 1.37 [95% CI: 1.11-1.70]), rs3757318 (OR = 1.33[1.05-1.69]), and rs3803662 (OR = 1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. Conclusion In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers. PMID:24289300

  19. Sipuleucel-T for the Treatment of Metastatic Hormone-Relapsed Prostate Cancer: A NICE Single Technology Appraisal; An Evidence Review Group Perspective.

    PubMed

    Simpson, Emma L; Davis, Sarah; Thokala, Praveen; Breeze, Penny R; Bryden, Peter; Wong, Ruth

    2015-11-01

    The National Institute for Health and Care Excellence (NICE) invited Dendreon, the company manufacturing sipuleucel-T, to submit evidence for the clinical and cost effectiveness of sipuleucel-T for asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer patients in whom chemotherapy is not yet clinically indicated, as part of NICE's single technology appraisal process. The comparator was abiraterone acetate (AA) or best supportive care (BSC). The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper describes the company submission (CS), ERG review, and subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost-effectiveness evidence of sipuleucel-T based upon the CS. Clinical-effectiveness data relevant to the decision problem were taken from three randomised controlled trials (RCTs) of sipuleucel-T and a placebo (PBO) comparator of antigen-presenting cells (APC) being re-infused (APC-PBO) (D9901, D9902A and D9902B), and one RCT (COU-AA-302) of AA plus prednisone vs. PBO plus prednisone. Two trials reported a significant advantage for sipuleucel-T in median overall survival compared with APC-PBO: for trial D9901, an adjusted hazard ratio (HR) 0.47; (95 % confidence interval [CI] 0.29, 0.76) p < 0.002; for D9902B, adjusted HR 0.78 (95 % CI 0.61, 0.98) p = 0.03. There was no significant difference between groups in D9902A, unadjusted HR 0.79 (95 % CI 0.48, 1.28) p = 0.331. Sipuleucel-T and APC-PBO groups did not differ significantly in time to disease progression, in any of the three RCTs. Most adverse events developed within 1 day of the infusion, and resolved within 2 days. The CS included an indirect comparison of sipuleucel-T (D9902B) and AA plus prednisone (COU-AA-302). As trials differed in prior use of chemotherapy, an analysis of only chemotherapy-naïve patients was included

  20. Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    PubMed

    Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

    2017-03-24

    As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

  1. Randomised trials for the Fitbit generation.

    PubMed

    Dempsey, Walter; Liao, Peng; Klasnja, Pedja; Nahum-Shani, Inbal; Murphy, Susan A

    2015-12-01

    Data from activity trackers and mobile phones can be used to craft personalised health interventions. But measuring the efficacy of these "treatments" requires a rethink of the traditional randomised trial.

  2. Functional analysis of a breast cancer-associated FGFR2 single nucleotide polymorphism using zinc finger mediated genome editing.

    PubMed

    Robbez-Masson, Luisa J; Bödör, Csaba; Jones, J Louise; Hurst, Helen C; Fitzgibbon, Jude; Hart, Ian R; Grose, Richard P

    2013-01-01

    Genome wide association studies have identified single nucleotide polymorphisms (SNP) within fibroblast growth factor receptor 2 (FGFR2) as one of the highest ranking risk alleles in terms of development of breast cancer. The potential effect of these SNPs, in intron two, was postulated to be due to the differential binding of cis-regulatory elements, such as transcription factors, since all the SNPs in linkage disequilibrium were located in a regulatory DNA region. A Runx2 binding site was reported to be functional only in the minor, disease associated allele of rs2981578, resulting in increased expression of FGFR2 in cancers from patients homozygous for that allele. Moreover, the increased risk conferred by the minor FGFR2 allele associates most strongly in oestrogen receptor alpha positive (ERα) breast tumours, suggesting a potential interaction between ERα and FGFR signalling. Here, we have developed a human cell line model system to study the effect of the putative functional SNP, rs2981578, on cell behaviour. MCF7 cells, an ERα positive breast cancer cell line homozygous for the wild-type allele were edited using a Zinc Finger Nuclease approach. Unexpectedly, the acquisition of a single risk allele in MCF7 clones failed to affect proliferation or cell cycle progression. Binding of Runx2 to the risk allele was not observed. However FOXA1 binding, an important ERα partner, appeared decreased at the rs2981578 locus in the risk allele cells. Differences in allele specific expression (ASE) of FGFR2 were not observed in a panel of 72 ERα positive breast cancer samples. Thus, the apparent increased risk of developing ERα positive breast cancer seems not to be caused by rs2981578 alone. Rather, the observed increased risk of developing breast cancer might be the result of a coordinated effect of multiple SNPs forming a risk haplotype in the second intron of FGFR2.

  3. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes

    PubMed Central

    Jia, Yijun; Weng, Ziyi; Wang, Chuanying; Zhu, Mingjie; Lu, Yunshu; Ding, Longlong; Wang, Yongkun; Cheng, Xianhua; Lin, Qing; Wu, Kejin

    2017-01-01

    Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80. PMID:28123543

  4. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    DTIC Science & Technology

    2015-07-01

    injury” throughout the respiratory tract. We have previously shown that gene expression from bronchial epithelial cells reflects the physiologic...of lung cancer, creates a “field of injury” throughout the respiratory tract. We have previously shown that gene expression from bronchial epithelial...for lung cancer.   INTRODUCTION:   Cigarette smoking, the major cause of lung cancer, creates a “field of injury” throughout the respiratory tract

  5. Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival

    PubMed Central

    Lu, Shun; Pardini, Barbara; Cheng, Bowang; Naccarati, Alessio; Huhn, Stefanie; Vymetalkova, Veronika; Vodickova, Ludmila; Buchler, Thomas; Hemminki, Kari; Vodicka, Pavel; Försti, Asta

    2014-01-01

    Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted. PMID:25350395

  6. Single nucleotide polymorphisms within interferon signaling pathway genes are associated with colorectal cancer susceptibility and survival.

    PubMed

    Lu, Shun; Pardini, Barbara; Cheng, Bowang; Naccarati, Alessio; Huhn, Stefanie; Vymetalkova, Veronika; Vodickova, Ludmila; Buchler, Thomas; Hemminki, Kari; Vodicka, Pavel; Försti, Asta

    2014-01-01

    Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted.

  7. Single-incision laparoscopic colorectal surgery for cancer: state of art.

    PubMed

    Cianchi, Fabio; Staderini, Fabio; Badii, Benedetta

    2014-05-28

    A number of clinical trials have demonstrated that the laparoscopic approach for colorectal cancer resection provides the same oncologic results as open surgery along with all clinical benefits of minimally invasive surgery. During the last years, a great effort has been made to research for minimizing parietal trauma, yet for cosmetic reasons and in order to further reduce surgery-related pain and morbidity. New techniques, such as natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopy (SIL) have been developed in order to reach the goal of "scarless" surgery. Although NOTES may seem not fully suitable or safe for advanced procedures, such as colectomies, SIL is currently regarded as the next major advance in the progress of minimally invasive surgical approaches to colorectal disease that is more feasible in generalized use. The small incision through the umbilicus allows surgeons to use familiar standard laparoscopic instruments and thus, perform even complex procedures which require extraction of large surgical specimens or intestinal anastomosis. The cosmetic result from SIL is also better because the only incision is made through the umbilicus which can hide the wound effectively after operation. However, SIL raises a number of specific new challenges compared with the laparoscopic conventional approach. A reduced capacity for triangulation, the repeated conflicts between the shafts of the instruments and the difficulties to achieve a correct exposure of the operative field are the most claimed issues. The use therefore of this new approach for complex colorectal procedures might understandingly be viewed as difficult to implement, especially for oncologic cases.

  8. Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

    PubMed Central

    Calcagno, A M; Fostel, J M; To, K K W; Salcido, C D; Martin, S E; Chewning, K J; Wu, C-P; Varticovski, L; Bates, S E; Caplen, N J; Ambudkar, S V

    2008-01-01

    Understanding the mechanisms of multidrug resistance (MDR) could improve clinical drug efficacy. Multidrug resistance is associated with ATP binding cassette (ABC) transporters, but the factors that regulate their expression at clinically relevant drug concentrations are poorly understood. We report that a single-step selection with low doses of anti-cancer agents, similar to concentrations reported in vivo, induces MDR that is mediated exclusively by ABCG2. We selected breast, ovarian and colon cancer cells (MCF-7, IGROV-1 and S-1) after exposure to 14 or 21 nM doxorubicin for only 10 days. We found that these cells overexpress ABCG2 at the mRNA and protein levels. RNA interference analysis confirmed that ABCG2 confers drug resistance. Furthermore, ABCG2 upregulation was facilitated by histone hyperacetylation due to weaker histone deacetylase 1-promoter association, indicating that these epigenetic changes elicit changes in ABCG2 gene expression. These studies indicate that the MDR phenotype arises following low-dose, single-step exposure to doxorubicin, and further suggest that ABCG2 may mediate early stages of MDR development. This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines. PMID:18382425

  9. A randomised trial of three or six courses of etoposide cyclophosphamide methotrexate and vincristine or six courses of etoposide and ifosfamide in small cell lung cancer (SCLC). II: Quality of life. Medical Research Council Lung Cancer Working Party.

    PubMed Central

    Bleehen, N. M.; Girling, D. J.; Machin, D.; Stephens, R. J.

    1993-01-01

    A total of 458 eligible patients, from 21 centres, with microscopically confirmed SCLC were allocated at random to three chemotherapy regimens, each given at 3-week intervals. In two regimens, etoposide, cyclophosphamide, methotrexate and vincristine were given for a total of either three courses (ECMV3) or six courses (ECMV6). In the third regimen, etoposide and ifosfamide were given for six courses (E16). Patients with limited disease also received radiotherapy to the primary site after the third course of chemotherapy in all three groups. As reported by clinicians, 59% of the ECMV3, 67% of the ECMV6 and 63% of the EI6 patients experienced moderate or severe adverse reactions to their chemotherapy. The major symptoms of disease, cough, haemoptysis, chest pain, anorexia, and dysphagia, were palliated in 63% or more of patients and the median duration of palliation was 63% or more of survival, the results being similar in the three groups. Among patients with poor overall condition, physical activity and breathlessness on admission, the proportions who improved were higher in the EI6 group but the differences were small. In all three groups, levels of anxiety fell substantially during treatment. Levels of depression were lower and showed little change. As assessed by patients using a daily diary card, the patterns of nausea, vomiting, activity and mood, associated with courses of chemotherapy were very similar in the three groups. In the EI6 group there was less dysphagia and better overall condition between courses, but these advantages need to be weighed against the inconvenience of the 24-h infusions required, compared with the 30-min infusions of the other two regimens. As reported in the companion paper (MRC Lung Cancer Working Party, 1993a) there was no statistically significant survival advantage to any of the three regimens, although the results do not exclude the possibility of a minor survival advantage with the two six-course regimens. In conclusion

  10. Single-walled carbon nanotube and graphene: Nano-delivery of Gambogic acid increases its cytotoxicty in various cancer cells

    NASA Astrophysics Data System (ADS)

    Saeed, Lamya M.

    Nanomedicine is a new branch of medicine that has been developed due to the critical need to treat challenging diseases, especially cancer since it remains a significant cause of morbidity and mortality worldwide and the second most common cause of death after heart disease in the USA. One of the most important health care applications of nanomedicine concerns the development of drug delivery systems. Graphene (Gn), an atom-thick carbon monolayer of sp2- bonded carbon atoms arranged in a two dimensional (2D) honeycomb crystal lattice, and single-walled carbon nanotubes (SWCNTs) (1D, tubular) are among the most promising nanomaterials with the capability of delivering drugs or small therapeutic molecules to cancerous cells. For example, they have been used as vehicles for the anti-cancer, low-toxicity drug Gambogic acid (GA). Here, the cytotoxicity of GA in breast (MCF-7), pancreatic (PANC-1), cervical (HELA), ovarian (NCI/ADR), and prostate (PC3) cancer cells was assessed to determine what effect nanodelivery by either Gn or SWCNTs had on the efficacy of this promising drug. The nanomaterials showed no toxicity at the concentrations used. The inhibition of cell proliferation and apoptosis of the cells was due to the effects of GA which was significantly enhanced by nanodelivery. Such delivery of GA by either Gn or SWCNTs represents a first step toward assessing their effectiveness in more complex, targeted nano-delivery in vivo settings and signals their potential application in the treatment of cancer.

  11. The influence of single nucleotide polymorphisms on the association between dietary acrylamide intake and endometrial cancer risk

    PubMed Central

    Hogervorst, Janneke G. F.; van den Brandt, Piet A.; Godschalk, Roger W. L.; van Schooten, Frederik-Jan; Schouten, Leo J.

    2016-01-01

    It is unclear whether the association between dietary acrylamide intake and endometrial cancer risk as observed in some epidemiological studies reflects a causal relationship. We aimed at clarifying the causality by analyzing acrylamide-gene interactions for endometrial cancer risk. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55–69 years. At baseline, a random subcohort of 2589 women was selected for a case cohort analysis approach. Acrylamide intake of subcohort members and endometrial cancer cases (n = 315) was assessed with a food frequency questionnaire. Single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair were assessed through a MassARRAY iPLEX Platform. Interaction between acrylamide and SNPs was assessed with Cox proportional hazards analysis, based on 11.3 years of follow-up. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions after adjustment for multiple testing. However, there were nominally statistically significant interactions for SNPs in acrylamide-metabolizing enzymes: CYP2E1 (rs915906 and rs2480258) and the deletions of GSTM1 and GSTT1. Although in need of confirmation, the interactions between acrylamide intake and CYP2E1 SNPs contribute to the evidence for a causal relationship between acrylamide and endometrial cancer risk. PMID:27713515

  12. Clinicopathological and Prognostic Factors in 106 Prostate Cancer Patients Aged ≤55 Years: A Single-Center Study in China

    PubMed Central

    Xu, Yan; Yang, Xueling; Si, Tongguo; Yu, Haipeng; Zhang, Weihao; Li, Yong; Guo, Zhi

    2016-01-01

    Background Early-onset prostate cancer patients (aged ≤55 years) from Western countries have been well characterized in previous studies. However, the clinicopathological and prognostic characteristics of early-onset Chinese prostate cancer patients have not yet been assessed. This study aimed to examine the clinicopathological and prognostic factors of prostate cancer patients aged ≤55 years in a single Chinese center. Material/Methods One hundred six prostate cancer patients aged ≤55 years with complete clinicopathological data who were treated at our hospital between January 2000 and June 2014 were selected for this study. Survival rate was investigated by Kaplan-Meier analysis, and prognostic factors were examined by univariate and multivariate analysis. Results The median time from the onset of symptoms to diagnosis was 3.5 months (range, 2–55 months). The median time after endocrine therapy to development of androgen-independent prostate cancer was 10.5 months. A total of 54 patients died (50.9%), of whom 96.2% died from prostate cancer. The 1-, 3-, and 5-year overall survival rates were 88.7%, 66.2%, and 36.0%, respectively. Univariate and multivariate analysis showed that T staging, visceral metastasis, pathological pattern, and Gleason sum were independent prognostic factors in these patients. Conclusions Prostate cancer patients aged ≤55 years are often omitted or misdiagnosed in China. Furthermore, the pathology patterns in this age group were mostly complicated with a high degree of malignancy. Late staging, visceral metastasis, pathological pattern, and high Gleason score were independent prognostic factors in these patients. Comprehensive therapy combined with local therapy is an effective treatment strategy. PMID:27771734

  13. A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer

    PubMed Central

    De Placido, S; De Laurentiis, M; De Lena, M; Lorusso, V; Paradiso, A; D'Aprile, M; Pistillucci, G; Farris, A; Sarobba, M G; Palazzo, S; Manzione, L; Adamo, V; Palmeri, S; Ferraù, F; Lauria, R; Pagliarulo, C; Petrella, G; Limite, G; Costanzo, R; Bianco, A R

    2005-01-01

    The sequential doxorubicin → CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF × 6 cycles (CMF); (b) doxorubicin × 4 cycles followed by CMF × 6 cycles (A → CMF); (c) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (CMF → GT); and (d) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (A → CMF → GT). The study used a 2 × 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A → CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A → CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556–0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489–1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555–0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54–1.32). A → CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. PMID:15668708

  14. Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites

    PubMed Central

    Family, Leila; Bensen, Jeannette T.; Troester, Melissa A.; Wu, Michael C.; Anders, Carey K.; Olshan, Andrew F.

    2015-01-01

    DNA damage recognition and repair is a complex system of genes focused on maintaining genomic stability. Recently, there has been a focus on how breast cancer susceptibility relates to genetic variation in the DNA bypass polymerases pathway. Race-stratified and subtype-specific logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between 22 single-nucleotide polymorphisms (SNPs) in seven bypass polymerase genes and breast cancer risk in the Carolina Breast Cancer Study, a population-based, case–control study (1,972 cases and 1,776 controls). We used SNP-set kernel association test (SKAT) to evaluate the multi-gene, multi-locus (combined) SNP effects within bypass polymerase genes. We found similar ORs for breast cancer with three POLQ SNPs (rs487848 AG/AA vs. GG; OR = 1.31, 95 % CI 1.03–1.68 for Whites and OR = 1.22, 95 % CI 1.00–1.49 for African Americans), (rs532411 CT/TT vs. CC; OR = 1.31, 95 % CI 1.02–1.66 for Whites and OR = 1.22, 95 % CI 1.00–1.48 for African Americans), and (rs3218634 CG/CC vs. GG; OR = 1.29, 95 % CI 1.02–1.65 for Whites). These three SNPs are in high linkage disequilibrium in both races. Tumor subtype analysis showed the same SNPs to be associated with increased risk of Luminal breast cancer. SKAT analysis showed no significant combined SNP effects. These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer. PMID:25417172

  15. Study shows colon and rectal tumors constitute a single type of cancer

    Cancer.gov

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  16. Therapeutic results in elderly patients with prostate cancer: chronological comparison in a single community hospital

    PubMed Central

    Okamura, Takehiko; Akita, Hidetoshi; Yamada, Kenji; Kobayashi, Daichi; Hirose, Yasuhiko; Kobayashi, Takahiro; Tanaka, Yutaro; Naiki, Taku; Yasui, Takahiro

    2016-01-01

    Objective: There are few reports of the long-term outcomes of elderly patients with prostate cancer. We analyzed data from our institution from the past 12 years, including the patient history, treatment methods, and prognosis of patients with prostate cancer aged 80 years or more. Patients and Methods: A total of 179 cases of prostate cancer in patients aged 80 years or more were retrospectively evaluated. We divided them chronologically into groups A, B, C, and D: Group A included 40 cases from 2002–2004; Group B, 48 cases from 2005–2007; Group C, 46 cases from 2008–2010; and Group D, 45 cases from 2011–2013. Results: Sixty-one (30%) patients changed treatment course. Interestingly, no cancer deaths occurred in the patients who changed treatment course. Although 14 (7.8%) cancer deaths occurred (A: B: C: D = 4: 4: 6: 0, respectively), all occurred in 2011 or later. Conclusion: In our study, over 50 patients who underwent treatment survived for 5 years or more. By treating prostate cancer in elderly patients when appropriate, we can lower the mortality rate due to prostate cancer. Our results support the active treatment of prostate cancer in elderly patients. PMID:27928457

  17. The benefits of cancer screening in kidney transplant recipients: a single-center experience.

    PubMed

    Kato, Taigo; Kakuta, Yoichi; Abe, Toyofumi; Yamanaka, Kazuaki; Imamura, Ryoichi; Okumi, Masayoshi; Ichimaru, Naotsugu; Takahara, Shiro; Nonomura, Norio

    2016-02-01

    The frequency of malignancy is increasing in kidney transplant recipients. Posttransplant malignancy (PTM) is a major cause of long-term graft survival inhibition. In this study, we evaluated the frequency and prognosis of PTM at our center and examined the efficacy of cancer screening. Between 1972 and 2013, 750 patients were followed-up at our center. Annual physical examinations and screenings were performed to detect PTM. We investigated the detail of two distinctive cancer groups: screening-detected cancers and symptom-detected cancers. Seventy-seven PTM were identified during the follow-up period. The mean age at the initial PTM detection was 43.6 ± 12.8 years. The mean interval from transplantation to cancer diagnosis was 134.5 ± 11.3 months. Among the 77 patients, posttransplant lymphoproliferative disease (PTLD) was the most common cancer (19.5%, 15/77), followed by renal cell carcinoma (15.6%, 12/77). Of the cancer cases, 46.8% (36/77) were detected via screening. The most frequently screening-detected cancer was renal cell carcinoma of the native kidney and breast cancer (22.2%, 8/36). However, it was difficult to detect PTLD, urothelial carcinoma, and colorectal cancer via screening. Interestingly, Cox proportional regression analyses revealed nonscreened recipients to be a significant prognostic factor for PTM (P < 0.001). This study is the first to report that appropriate screening tests play a key role in early PTM diagnosis and lead to reduce the mortality rate in kidney transplant recipients. These findings support the provision of long-term appropriate screening for kidney transplant recipients.

  18. Targeting single-walled carbon nanotubes for the treatment of breast cancer using photothermal therapy

    NASA Astrophysics Data System (ADS)

    Neves, Luis Filipe Ferreira

    To develop a therapeutic system with cancer cell selectivity, the present study evaluated a possible specific and localized tumor treatment. Phosphatidylserine (PS) exposure on the external face of the cell membrane is almost completely exclusive to cancer cells and endothelial cells in the tumor vasculature. The human protein annexin V is known to have strong calcium-dependent binding to anionic phospholipids such as PS. This protein was studied for targeting single-walled carbon nanotubes (SWNTs) to the vasculature of breast tumors. The synthesis of the protein annexin V, by a pET vector in Escherichia coli, constitutes the first phase of this study. Recombinant annexin V was purified from the cell lysate supernatant by immobilized metal affinity chromatography. The overall production of purified annexin V protein was 50 mg/L. The binding ability of the protein annexin V was evaluated by determining the dissociation constant when incubated with proliferating human endothelial cells in vitro. The dissociation constant, Kd, was measured to be 0.8 nM, indicating relatively strong binding. This value of Kd is within the range reported in the literature. Single-walled carbon nanotubes (SWNTs) were functionalized with annexin V using two intermediate linkers (containing FMOC and DSPE) resulting in stable suspensions. The SWNT and protein concentrations were 202 mg/L and 515 mg/L, respectively, using the linker with DSPE (average of nine preparations). The conjugation method that used the DSPE-PEG-maleimide linker allowed to successfully conjugate the SWNTs with final concentrations approximately five times higher than the linker containing FMOC. The conjugation method used has a non-covalent nature, and therefore the optical properties of the nanotubes were preserved. The conjugate was also visually observed using atomic force microscopy (AFM), allowing to verify the presence of the protein annexin V on the surface of the nanotubes, with an height ranging between 2

  19. Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes.

    PubMed

    Kanick, Stephen Chad; van der Leest, Cor; Aerts, Joachim G J V; Hoogsteden, Henk C; Kascáková, Slávka; Sterenborg, Henricus J C M; Amelink, Arjen

    2010-01-01

    We describe the incorporation of a single-fiber reflectance spectroscopy probe into the endoscopic ultrasound fine-needle aspiration (EUS-FNA) procedure utilized for lung cancer staging. A mathematical model is developed to extract information about the physiological and morphological properties of lymph tissue from single-fiber reflectance spectra, e.g., microvascular saturation, blood volume fraction, bilirubin concentration, average vessel diameter, and Mie slope. Model analysis of data from a clinical pilot study shows that the single-fiber reflectance measurement is capable of detecting differences in the physiology between normal and metastatic lymph nodes. Moreover, the clinical data show that probe manipulation within the lymph node can perturb the in vivo environment, a concern that must be carefully considered when developing a sampling strategy. The data show the feasibility of this novel technique; however, the potential clinical utility has yet to be determined.

  20. Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes

    NASA Astrophysics Data System (ADS)

    Kanick, Stephen Chad; van der Leest, Cor; Aerts, Joachim G. J. V.; Hoogsteden, Henk C.; Kaščáková, Slávka; Sterenborg, Henricus J. C. M.; Amelink, Arjen

    2010-01-01

    We describe the incorporation of a single-fiber reflectance spectroscopy probe into the endoscopic ultrasound fine-needle aspiration (EUS-FNA) procedure utilized for lung cancer staging. A mathematical model is developed to extract information about the physiological and morphological properties of lymph tissue from single-fiber reflectance spectra, e.g., microvascular saturation, blood volume fraction, bilirubin concentration, average vessel diameter, and Mie slope. Model analysis of data from a clinical pilot study shows that the single-fiber reflectance measurement is capable of detecting differences in the physiology between normal and metastatic lymph nodes. Moreover, the clinical data show that probe manipulation within the lymph node can perturb the in vivo environment, a concern that must be carefully considered when developing a sampling strategy. The data show the feasibility of this novel technique; however, the potential clinical utility has yet to be determined.

  1. Association of Single Nucleotide Polymorphisms in Wnt Signaling Pathway Genes with Breast Cancer in Saudi Patients

    PubMed Central

    Shaik, Jilani Purusottapatnam; Alabdulkarim, Huda A.; Ajaj, Sana Abdulla; Khan, Zahid

    2013-01-01

    Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni's correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas. PMID:23516639

  2. Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients.

    PubMed

    Alanazi, Mohammad Saud; Parine, Narasimha Reddy; Shaik, Jilani Purusottapatnam; Alabdulkarim, Huda A; Ajaj, Sana Abdulla; Khan, Zahid

    2013-01-01

    Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni's correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas.

  3. Prediction of Breast Cancer Metastasis by Gene Expression Profiles: A Comparison of Metagenes and Single Genes

    PubMed Central

    Burton, Mark; Thomassen, Mads; Tan, Qihua; Kruse, Torben A.

    2012-01-01

    Background The popularity of a large number of microarray applications has in cancer research led to the development of predictive or prognostic gene expression profiles. However, the diversity of microarray platforms has made the full validation of such profiles and their related gene lists across studies difficult and, at the level of classification accuracies, rarely validated in multiple independent datasets. Frequently, while the individual genes between such lists may not match, genes with same function are included across such gene lists. Development of such lists does not take into account the fact that genes can be grouped together as metagenes (MGs) based on common characteristics such as pathways, regulation, or genomic location. Such MGs might be used as features in building a predictive model applicable for classifying independent data. It is, therefore, demanding to systematically compare independent validation of gene lists or classifiers based on metagene or individual gene (SG) features. Methods In this study we compared the performance of either metagene-or single gene-based feature sets and classifiers using random forest and two support vector machines for classifier building. The performance within the same dataset, feature set validation performance, and validation performance of entire classifiers in strictly independent datasets were assessed by 10 times repeated 10-fold cross validation, leave-one-out cross validation, and one-fold validation, respectively. To test the significance of the performance difference between MG- and SG-features/classifiers, we used a repeated down-sampled binomial test approach. Results MG- and SG-feature sets are transferable and perform well for training and testing prediction of metastasis outcome in strictly independent data sets, both between different and within similar microarray platforms, while classifiers had a poorer performance when validated in strictly independent datasets. The study showed that MG

  4. Spanning the genomics era: the vital role of a single institution biorepository for childhood cancer research over a decade

    PubMed Central

    Zhou, Li

    2015-01-01

    The ‘genomics era’ is considered to have begun with the commencement of the Human Genome Project. As translational genomic studies can only be established when human tissue samples are available for analysis, biospecimens are now proven to be an essential element for their success. During the genomics era the necessity for more extensive biobanking infrastructure has been highlighted. With the increased number of genomic studies into cancer, it is considered that the availability of biospecimens will become the rate limiting step. Despite the efforts in international biobanking, translational genomics is hampered when there low numbers of biospecimens for a particular rare diseases and is most apparent for paediatric cancer. As there is a call for biobanking practice to be responsive to the current experimental needs of the time and for more expansive systems of tissue procurement to be established we have asked the question what role does a single institution biorepository play in the current highly networked world of translational genomics. Here we describe such a case. The Tumour Bank at The Children’s Hospital at Westmead (TB-CHW) in the western suburbs of Sydney was formally established in 1998 as a key resource for translational paediatric cancer research. During the genomics era, we show that the TB-CHW has developed into a key biospecimen repository for the cancer research community, during which time it has increasingly found itself having a vital role in the establishment of translational genomics for paediatric cancer. Here we detail metrics that demonstrate how as a single institution biorepository, the TB-CHW has been a strong participant in the advancement of translational genomics throughout the genomics era. This paper describes the significant contribution of a single institutional hospital embedded tumour biobank to the genomic research community. Despite the increased stringencies placed on biobanking practice, the TB-CHW has shown that a

  5. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Jørgensen, Jesper Tranekjær; Norregaard, Kamilla; Tian, Pengfei; Bendix, Poul Martin; Kjaer, Andreas; Oddershede, Lene B.

    2016-08-01

    Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform to quantitatively correlate the heat generation of plasmonic nanoparticles with their potential as cancer killing agents. In vitro, the heat generation and absorption cross-section of single irradiated nanoparticles were quantified using a temperature sensitive lipid-based assay and compared to their theoretically predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant silica-gold nanoshells (AuNSs) and benchmarked this against the heating of colloidal spherical, solid gold nanoparticles (AuNPs). As expected, both in vitro and in vivo the heat generation of the resonant AuNSs performed superior compared to the non-resonant AuNPs. Furthermore, the results showed that PET imaging could be reliably used to monitor early treatment response of photothermal treatment. This multidisciplinary approach provides a much needed platform to benchmark the emerging plethora of novel plasmonic nanoparticles for their potential for photothermal cancer therapy.

  6. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

    PubMed Central

    Jørgensen, Jesper Tranekjær; Norregaard, Kamilla; Tian, Pengfei; Bendix, Poul Martin; Kjaer, Andreas; Oddershede, Lene B.

    2016-01-01

    Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform to quantitatively correlate the heat generation of plasmonic nanoparticles with their potential as cancer killing agents. In vitro, the heat generation and absorption cross-section of single irradiated nanoparticles were quantified using a temperature sensitive lipid-based assay and compared to their theoretically predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant silica-gold nanoshells (AuNSs) and benchmarked this against the heating of colloidal spherical, solid gold nanoparticles (AuNPs). As expected, both in vitro and in vivo the heat generation of the resonant AuNSs performed superior compared to the non-resonant AuNPs. Furthermore, the results showed that PET imaging could be reliably used to monitor early treatment response of photothermal treatment. This multidisciplinary approach provides a much needed platform to benchmark the emerging plethora of novel plasmonic nanoparticles for their potential for photothermal cancer therapy. PMID:27481537

  7. Single-access laparoscopic approach in the surgical treatment of endometrial cancer: A single-institution experience and review of literature

    PubMed Central

    Corrado, Giacomo; Cutillo, Giuseppe; Pomati, Giulia; Mancini, Emanuela; Baiocco, Ermelinda; Patrizi, Lodovico; Saltari, Maria; Barletta, Francesco; Patani, Fabiola; Vizza, Enrico

    2016-01-01

    BACKGROUND: The aim of this study was to assess the surgical and oncological outcome for the management of endometrial cancer (EC) by laparoendoscopic single-site surgery (LESS). PATIENTS AND METHODS: We performed a retrospective chart review of patients who underwent a LESS for EC. All the patients were treated by the same surgical team between July 2009 and June 2013 at the Gynaecologic Oncologic Unit, Regina Elena National Cancer Institute, Rome, Italy. RESULTS: A total of 50 women were included, with a median age of 45 years (range, 39-84 years) and a median body mass index (BMI) of 21.8 kg/m2 (range, 19-48 kg/m2). Median operative time was 100 min (range, 50-240 min), median blood loss was 90 mL (range, 10-300 mL) and median hospital stay was 3 days (range, 2-9 days). The median number of pelvic lymph nodes retrieved was 14 (range, 5-20). No intraoperative complications occurred, but there were 4 postoperative complications. Two patients required a laparoscopic conversion. The median follow-up was 36 months (range, 16-62 months) and no recurrence occurred. CONCLUSION: Our report showed that the LESS approach in the treatment of early EC can be a safe and reliable technique in terms of surgical and oncological outcomes. PMID:27609329

  8. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-Tae; Iqbal, Samir M.

    2015-09-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  9. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.

    PubMed

    Islam, Muhymin; Bellah, Mohammad Motasim; Sajid, Adeel; Hasan, Mohammad Raziul; Kim, Young-tae; Iqbal, Samir M

    2015-09-16

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  10. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    PubMed Central

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2015-01-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer. PMID:26373820

  11. Preparation and characterization of anti-tissue factor single-chain variable fragment antibody for cancer diagnosis.

    PubMed

    Sato, Ryuta; Obonai, Toshifumi; Tsumura, Ryo; Tsumoto, Kouhei; Koga, Yoshikatsu; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2014-12-01

    Tissue factor (TF), which serves as the initiator of the extrinsic blood coagulation cascade, has been found to be overexpressed in various solid tumors, especially brain tumors, pancreatic cancer, and gastric cancer. Overexpression of TF is considered to contribute to the high incidence of thrombotic complications and poor prognosis in patients with such cancers. Therefore, detection or targeting of TF may be a promising approach for the diagnosis and treatment of solid tumors that are known to overexpress the protein. Here, we used the recombinant DNA technology to develop an anti-TF single-chain Fv (scFv) of small size and high affinity for its target. The biochemical characteristics of the anti-TF scFv were evaluated using surface plasmon resonance (SPR) sensing and flow cytometry. The data obtained showed that the affinity of the anti-TF scFv was 2.04 × 10(-8) (KD), and that the protein showed significant binding to the cancer cells. Then, Alexa 647-labeled anti-TF scFv and anti-TF IgG were administered to mice bearing chemically induced spontaneous tumors. The maximum tumor to background ratios of anti-TF scFv and anti-TF IgG were obtained 3 and 24 h after the injections, respectively. This study indicates anti-TF scFv may be suitable as an imaging probe for the diagnosis of solid tumors.

  12. Psychotherapy and phosphodiesterase-5 inhibitor in early rehabilitation after radical prostatectomy: a prospective randomised controlled trial.

    PubMed

    Naccarato, A M E P; Reis, L O; Ferreira, U; Denardi, F

    2016-12-01

    The aim of this study was to evaluate the impact of group psychotherapy and the use of a phosphodiesterase-5 inhibitor (PDE-5i) in the early rehabilitation stage of patients with prostate cancer undergoing radical prostatectomy (RP). Fifty-six patients undergoing RP for prostate cancer were randomised into four groups, and 53 completed the protocol: Group 1 - control (n = 11), Group 2 - group psychotherapy (n = 16), Group 3 - lodenafil 80 mg/one tablet per week (n = 12) and Group 4 - group psychotherapy + lodenafil 80 mg/one tablet per week (n = 14). The groups were individually evaluated for erectile function (IIEF-5) and quality of life - QoL (SF-36) weekly, with two meetings held a week apart before the RP and 12 weekly meetings after surgery. The ages ranged from 39 to 76 years, average 61.84. There were no significant medication side effects. Only Group 4 showed improvement in intimacy with a partner and satisfaction with their sex life (P = 0.045 and P = 0.013 respectively), and with no significant worsening of the IIEF-5 (P = 0.250) reported. All groups showed worsening in the final result of the role limitations caused by physical problems (P = 0.009) and role limitations caused by emotional problems (P = 0.002) of the SF-36, but Group 4 had a significantly higher score for the role limitations caused by physical problems (P = 0.009) than the other groups. In conclusion, precocious integral treatment involving group psychotherapy and PDE-5i before and after RP led to less deterioration of erectile function and other domains related to physical aspects (SF-36), with improvement in intimacy with their partner and satisfaction in their sex life, being superior to single treatments.

  13. Modern applications of high energy ion beams: From "single-event burnout" to human eye cancer treatment

    NASA Astrophysics Data System (ADS)

    Homeyer, H.; Mahnke, H.-E.

    1996-12-01

    Energetic ion beams, originally the domain of nuclear physics, become increasingly important tools in many other fields of research and development. The choice of ion species and ion energy allows an enormously wide variation of the penetration depth and of the amount of the electronic stopping power. These features are utilized to modify or damage materials and living tissues in a specific way. Materials modification with energetic ion beams is one of the central aims of research and development at the ion beam laboratory, ISL-Berlin, a center for ion-beam applications at the Hahn-Meitner-Institut Berlin. In particular, energetic protons will be used for eye cancer treatment. Selected topics such as the "single-event burnout" of high power diodes and the eye cancer therapy setup will be presented in detail.

  14. High-Throughput Single-Cell Derived Sphere Formation for Cancer Stem-Like Cell Identification and Analysis

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Chih; Ingram, Patrick N.; Fouladdel, Shamileh; McDermott, Sean P.; Azizi, Ebrahim; Wicha, Max S.; Yoon, Euisik

    2016-06-01

    Considerable evidence suggests that many malignancies are driven by a cellular compartment that displays stem cell properties. Cancer stem-like cells (CSCs) can be identified by expression of cell surface markers or enzymatic activity, but these methods are limited by phenotypic heterogeneity and plasticity of CSCs. An alternative phenotypic methodology based on in-vitro sphere formation has been developed, but it is typically labor-intensive and low-throughput. In this work, we present a 1,024-microchamber microfluidic platform for single-cell derived sphere formation. Utilizing a hydrodynamic capturing scheme, more than 70% of the microchambers capture only one cell, allowing for monitoring of sphere formation from heterogeneous cancer cell populations for identification of CSCs. Single-cell derived spheres can be retrieved and dissociated for single-cell analysis using a custom 96-gene panel to probe heterogeneity within the clonal CSC spheres. This microfluidic platform provides reliable and high-throughput sphere formation for CSC identification and downstream clonal analysis.

  15. High-Throughput Single-Cell Derived Sphere Formation for Cancer Stem-Like Cell Identification and Analysis

    PubMed Central

    Chen, Yu-Chih; Ingram, Patrick N.; Fouladdel, Shamileh; McDermott, Sean P.; Azizi, Ebrahim; Wicha, Max S.; Yoon, Euisik

    2016-01-01

    Considerable evidence suggests that many malignancies are driven by a cellular compartment that displays stem cell properties. Cancer stem-like cells (CSCs) can be identified by expression of cell surface markers or enzymatic activity, but these methods are limited by phenotypic heterogeneity and plasticity of CSCs. An alternative phenotypic methodology based on in-vitro sphere formation has been developed, but it is typically labor-intensive and low-throughput. In this work, we present a 1,024-microchamber microfluidic platform for single-cell derived sphere formation. Utilizing a hydrodynamic capturing scheme, more than 70% of the microchambers capture only one cell, allowing for monitoring of sphere formation from heterogeneous cancer cell populations for identification of CSCs. Single-cell derived spheres can be retrieved and dissociated for single-cell analysis using a custom 96-gene panel to probe heterogeneity within the clonal CSC spheres. This microfluidic platform provides reliable and high-throughput sphere formation for CSC identification and downstream clonal analysis. PMID:27292795

  16. Nanoparticle Induced Cell Magneto-Rotation: Monitoring Morphology, Stress and Drug Sensitivity of a Suspended Single Cancer Cell

    PubMed Central

    Elbez, Remy; McNaughton, Brandon H.; Patel, Lalit; Pienta, Kenneth J.; Kopelman, Raoul

    2011-01-01

    Single cell analysis has allowed critical discoveries in drug testing, immunobiology and stem cell research. In addition, a change from two to three dimensional growth conditions radically affects cell behavior. This already resulted in new observations on gene expression and communication networks and in better predictions of cell responses to their environment. However, it is still difficult to study the size and shape of single cells that are freely suspended, where morphological changes are highly significant. Described here is a new method for quantitative real time monitoring of cell size and morphology, on single live suspended cancer cells, unconfined in three dimensions. The precision is comparable to that of the best optical microscopes, but, in contrast, there is no need for confining the cell to the imaging plane. The here first introduced cell magnetorotation (CM) method is made possible by nanoparticle induced cell magnetization. By using a rotating magnetic field, the magnetically labeled cell is actively rotated, and the rotational period is measured in real-time. A change in morphology induces a change in the rotational period of the suspended cell (e.g. when the cell gets bigger it rotates slower). The ability to monitor, in real time, cell swelling or death, at the single cell level, is demonstrated. This method could thus be used for multiplexed real time single cell morphology analysis, with implications for drug testing, drug discovery, genomics and three-dimensional culturing. PMID:22180784

  17. Cytotoxicity of blended versus single medicinal mushroom extracts on human cancer cell lines: contribution of polyphenol and polysaccharide content.

    PubMed

    Durgo, Ksenija; Koncar, Mladen; Komes, Drazenka; Belscak-Cvitanovic, Ana; Franekic, Jasna; Jakopovich, Ivan; Jakopovich, Neven; Jakopovich, Boris

    2013-01-01

    The use of mushrooms contributes to human nutrition by providing low lipid content of lipids and high dietary fiber content, as well as significant content of other biologically active compounds such as polysaccharides, minerals, vitamins, and polyphenolic antioxidants. This study aimed to determine the content of polyphenols and polysaccharides, as well as the cytotoxic and antioxidative properties of several medicinal mushroom preparations. The content of total phenols and flavonoids of preparations of blended mushroom extracts (Lentifom, Super Polyporin, Agarikon, Agarikon Plus, Agarikon.1, and Mykoprotect.1) was evaluated quantitatively by using ultraviolet-visible spectroscopy spectrophotometric methods. The antioxidant capacity of the preparations was evaluated using the ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and ferric reducing/antioxidant power assays. The content of water-soluble polysaccharides was determined using a specific gravimetric method, based on ethanol precipitation. To determine cytotoxic effects of single and blended mushroom extracts, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red assays were conducted using human small cell lung cancer, lung adenocarcinoma, colon cancer, and brain astrocytoma cancer cells. The obtained results suggest that due to the significant content of beneficial polyphenolic antioxidants and soluble polysaccharides, use of these mushroom preparations is beneficial in maintaining good health, as well as in the prevention and adjuvant biotherapy of various human pathological aberrations. These results reveal that these extracts exhibit different cytotoxic effects on tumor cells originating from different tissues. In addition, the comparison of investigated blended mushroom extracts with three well-known commercial mushroom products derived from single mushroom species or single mushroom compounds shows that blended mushroom extracts exhibit significantly stronger

  18. Extralevator abdominoperineal excision versus conventional surgery for low rectal cancer: a single surgeon experience

    PubMed Central

    Neşşar, Gürel; Demirbağ, Ali Eba; Celep, Bahadır; Elbir, Orhan Hayri; Kayaalp, Cüneyt

    2016-01-01

    Objective Extralevator abdominoperineal excision (ELAPE) reduces the risk of positive circumferential resection margin (CRM) and of intraoperative perforation (IOP), both of which are associated with high local recurrence rates and poor survival outcomes for rectal cancer. The aim of this study was to compare the results of ELAPE with conventional abdominoperineal excision (APE) for low rectal cancer. Material and Methods A total of 25 consecutive patients underwent ELAPE for low rectal cancer between November 2008 and September 2011. Fifty-six patients treated by conventional APE prior to 2008 were selected from our rectal cancer database for comparison as a historical cohort. Results The mean follow-up was 44.7 months in the ELAPE group, and 70.6 months in the APE group. Patients undergoing ELAPE had a lower CRM positivity and IOP rate than APE (12% vs. 20%, p=0,531; 4% vs. 8,9%, p=0,826; respectively). The ELAPE group was associated with higher perineal wound complications than the APE group (16.0% vs. 1.8%, p=0.030). Local recurrence rates for patients in both groups did not differ significantly (4.0% vs. 3.6%, p=1.0). Conclusion The results of this study suggest that ELAPE technique was associated with less CRM involvement and reduced rates of IOP but markedly higher rates of postoperative perineal complications occurred as compared to conventional surgery. ELAPE must be reserved for advanced low rectal cancers. PMID:28149119

  19. Time trends in breast cancer survival: experience in a single centre, 1975-89.

    PubMed Central

    Bradburn, M. J.; Altman, D. G.; Smith, P.; Fentiman, I. S.; Rubens, R. D.

    1998-01-01

    The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s. PMID:9667672

  20. African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer

    PubMed Central

    Kato, Ikuko; Cichon, Michelle; Yee, Cecilia L.; Land, Susan; Korczak, Jeannette F.

    2009-01-01

    Background African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. Methods A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. Results The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio(OR)=2.34, 95%confidence interval (CI): 1.23–4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95% CI: 1.29–6.99). Conclusion These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases. PMID:19679043

  1. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial

    PubMed Central

    Chevalier, X; Jerosch, J; Goupille, P; van Dijk, N; Luyten, F P; Scott, D L; Bailleul, F; Pavelka, K

    2010-01-01

    Objectives: The primary objective was to compare a single, 6 ml, intra-articular injection of hylan G-F 20 with placebo in patients with symptomatic knee osteoarthritis. The safety of a repeat injection of hylan G-F 20 was also assessed. Methods: Patients with primary osteoarthritis knee pain were randomly assigned to arthrocentesis plus a 6 ml intra-articular injection of either hylan G-F 20 or placebo in a prospective, double-blind (one injector/one blinded observer) study. Results were evaluated at 4, 8, 12, 18 and 26 weeks post-injection. The primary outcome criterion was change from baseline over 26 weeks in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index A pain. Secondary outcome measures included WOMAC A1 and C, patient global assessment (PGA) and clinical observer global assessment (COGA) and Outcome Measures in Rheumatology, Osteoarthritis Research Society International responder rates. A 4-week, open, repeat treatment phase evaluated safety only. Results: A total of 253 patients (Kellgren–Lawrence grade II or III) was randomly assigned. Patients receiving hylan G-F 20 experienced statistically significantly greater improvements in WOMAC A pain scores (−0.15, SE 0.076, p = 0.047), and several of the secondary outcome measures (WOMAC A1, PGA and COGA), than patients receiving placebo. There was no difference between the safety results of the two groups. No increased risk of local adverse events was observed in the open, repeat treatment phase. Conclusions: This placebo-controlled study demonstrated that, in patients with knee osteoarthritis, a single 6 ml intra-articular injection of hylan G-F 20 is safe and effective in providing statistically significant, clinically relevant pain relief over 26 weeks, with a modest difference versus placebo. Trial registration number: NCT00131352. PMID:19304567

  2. Improving venous ulcer healing: designing and reporting randomised controlled trials.

    PubMed

    Weller, Carolina D; McNeil, John; Evans, Sue; Reid, Christopher

    2010-02-01

    The randomised controlled trial (RCT) is often considered the gold standard for judging the benefits of treatments. The application of randomised controlled clinical trials to treatments of venous ulcer healing has lagged behind that of other areas of medicine. To interpret the results of an RCT, readers must understand a variety of aspects of their design, analysis and interpretation. Venous ulcer disease has a high prevalence and has a significant socioeconomic impact in most parts of the world. The management of venous ulcers causes a considerable strain on the health system and is likely to worsen in future. The multi-layer high compression system is described as the current gold standard for treating venous ulcers. A recent meta-analysis of bandaging systems found that multi-layer compression bandages appeared to be superior to single-layer bandages in promoting venous ulcer healing. However, it was noted that many of the studies had small sample sizes and the quality of research in the area was poor. The consolidating standards of reporting trials (CONSORT) statement can help clinicians to discern high-quality studies from ones of poorer quality. This paper discusses how CONSORT can help clinicians and researchers to design and report quality studies to contribute to evidence-based venous ulcer healing.

  3. Development of a hyperimmune anti-MUC-1 single chain antibody fragments phage display library for targeting breast cancer.

    PubMed

    Winthrop, M D; DeNardo, S J; DeNardo, G L

    1999-10-01

    Radioimmunotherapy (RIT) has demonstrated potential for improving clinical cancer therapy. Optimizing the approach has proven difficult thus far. Antibody phage display libraries provide unique molecules that could improve RIT. A phage display library of single chain antibody fragments (scFv) against the MUC-1 mucin molecule, which is expressed on 90% of human breast cancers, was produced from the spleen cells of MUC-1 hyperimmunized BALB/c mice. Increased serum IgG levels, 15 times baseline, were detected following the third immunization. RNA from the spleen cells was isolated, cDNA was made, and variable heavy and variable light immunoglobulin chain gene regions were amplified using PCR technology. The variable heavy and variable light chain gene regions were combined with a flexible linker, ligated into the pCANTAB 5E phagemid vector, and electroporated into TG1 Escherichia coli cells. A library of 10(7) initial colonies was compiled. Forty-six of 288 colonies screened for reactivity demonstrated binding to MUC-1-expressing MCF-7 breast cancer cell membrane fragments. Anti-MUC-1 library diversity evaluated by BstNI digest demonstrated that 52% of the anti-MUC-1 scFv binding MCF-7 possessed individual banding patterns representative of approximately 5 x 10(5) colonies likely able to recognize distinct epitopes present on MUC-1 positive human breast cancers. In summary, the anti-MUC-1 scFv antibody phage library contains diverse scFv molecules, which should provide unique characteristics and epitope recognition. These molecules will be used in the development of pretargeting RIT strategies designed to improve the clinical outcome of patients with breast cancer.

  4. Photo-nano immunotherapy for metastatic breast cancer using synergistic single-walled carbon nanotubes and glycated chitosan

    NASA Astrophysics Data System (ADS)

    Zhou, Feifan; Hasanjee, Aamr; Doughty, Austin; West, Connor; Liu, Hong; Chen, Wei R.

    2015-03-01

    In our previous work, we constructed a multifunctional nano system, using single-walled carbon nanotube (SWNT) and glycated chitosan (GC), which can synergize photothermal and immunological effects. To further confirm the therapy efficacy, with a metastatic mouse mammary tumor model (4T1), we investigate the therapy effects and immune response induced by SWNT-GC, under laser irradiation. Laser+SWNT-GC treatment not only suppressed the prime tumor, but also induced antitumor immune response. It could be developed into a promising treatment modality for the metastatic breast cancer.

  5. Protocol of a randomised phase III clinical trial of sequential capecitabine or 5-fluorouracil plus bevacizumab (Cape/5-FU-Bmab) to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab in advanced colorectal cancer: the C-cubed (C3) study

    PubMed Central

    Mishima, Hideyuki; Sawaki, Akira; Shimokawa, Mototsugu; Inukai, Michio; Shinozaki, Katsunori; Tanioka, Hiroaki; Nasu, Junichiro; Nishina, Tomohiro; Hazama, Shoichi; Okajima, Masazumi; Yamaguchi, Yoshiyuki

    2016-01-01

    Introduction Results from several randomised trials suggest that the sequential use of cytotoxic agents in patients with metastatic colorectal cancer (mCRC) has the potential to improve overall survival compared with combination chemotherapy. This study is designed to investigate whether sequential treatment with bevacizumab-based first-line treatment with oxaliplatin is superior to combination treatment of mCRC. Methods and analysis The C-cubed (C3) study is a two-arm, multicentre, open-label, randomised phase III trial in Japan comparing the efficacy and safety of sequential capecitabine or 5-fluorouracil plus bevacizumab (Cape/5-FU-Bmab) with escalation to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab as the first-line treatment of mCRC. In the sequential arm (Arm A: oxaliplatin ‘wait-and-go’), treatment escalation from Cape/5-FU-Bmab to CapeOX/mFOLFOX6-Bmab is recommended in the case of progressive disease. In the combination arm (Arm B: oxaliplatin ‘stop-and-go’), de-escalation from CapeOX/mFOLFOX6-Bmab to Cape/5-FU-Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6-Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin after 12 weeks of treatment not caused by oxaliplatin-associated toxicity. A target sample size of 304 evaluable patients is considered sufficient to validate an expected HR for time to failure of strategy of the sequential approach ‘wait-and-go’ compared to the combination approach ‘stop-and go’ with 80% power and 2-sided 5% α in case of a true HR<0.69. Ethics and dissemination This study is conducted according to the standards of Good Clinical Practice and in compliance with the Declaration of Helsinki 2013 and local regulations, and has been submitted and approved by the Ethical Committee of the Non-Profit Organization MINS Institutional Review Board. The protocol

  6. Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis

    PubMed Central

    Court, Colin M; Ankeny, Jacob S; Hou, Shuang; Tseng, Hsian-Rong; Tomlinson, James S

    2016-01-01

    Pancreatic cancer (PC) is the fourth most common cause of cancer-related death in the USA, primarily due to late presentation coupled with an aggressive biology. The lack of adequate biomarkers for diagnosis and staging confound clinical decision-making and delay potentially effective therapies. Circulating tumor cells (CTCs) are a promising new biomarker in PC. Preliminary studies have demonstrated their potential clinical utility, and newer CTC isolation platforms have the potential to provide clinicians access to tumor tissue in a reliable, real-time manner. Such a ‘liquid biopsy’ has been demonstrated in several cancers, and small studies have demonstrated its potential applications in PC. This article reviews the available literature on CTCs as a biomarker in PC and presents the latest innovations in CTC research as well as their potential applications in PC. PMID:26390158

  7. Two-fraction high-dose-rate brachytherapy within a single day combined with external beam radiotherapy for prostate cancer: single institution experience and outcomes

    PubMed Central

    Liu, Junyang; Kaidu, Motoki; Sasamoto, Ryuta; Ayukawa, Fumio; Yamana, Nobuko; Sato, Hiraku; Tanaka, Kensuke; Kawaguchi, Gen; Ohta, Atsushi; Maruyama, Katsuya; Abe, Eisuke; Kasahara, Takashi; Nishiyama, Tsutomu; Tomita, Yoshihiko; Aoyama, Hidefumi

    2016-01-01

    We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- (n =5; 3.2%), intermediate- (n =36; 23.1%) and high-risk (n =115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary. PMID:26983988

  8. Real life cancer comorbidity in Greek patients with diabetes mellitus followed up at a single diabetes center: an unappreciated new diabetes complication.

    PubMed

    Thanopoulou, Anastasia; Pectasides, Demetrios

    2014-01-01

    We determined cancer comorbidity in patients with diabetes followed up at a single Greek academic clinic and investigated the potential related factors. Cancer comorbidity was prospectively recorded for all patients with type 2 (T2DM, n = 759) or type 1 (T1DM, n = 134) diabetes of at least 10-year duration examined during one year. Patient characteristics, diabetes age of onset, duration, treatment, control, and complication rates were compared between subjects with and without cancer. Moreover, a retrospective collection of data from similar patients examined for the first time during the last 25 years, but lost to follow-up, after at least one-year's regular visits, was performed. In regularly followed-up T2DM patients cancer comorbidity was 12.6%. Patients with cancer were older and more frequently smokers. Prostate cancer was the most frequent (24.0%) type. In T1DM cancer comorbidity was 3.0%. Similar rates of comorbidity and types of cancer were observed in lost to follow-up patients. In conclusion, our patients with T2DM of at least 10-year' duration show high cancer comorbidity. No specific characteristics discriminate patients with cancer. Therefore presymptomatic cancer detection and prevention strategies may have to be incorporated into the annual systematic evaluation of our patients.

  9. Single-strand DNA library preparation improves sequencing of formalin-fixed and paraffin-embedded (FFPE) cancer DNA

    PubMed Central

    Stiller, Mathias; Sucker, Antje; Griewank, Klaus; Aust, Daniela; Baretton, Gustavo Bruno; Schadendorf, Dirk; Horn, Susanne

    2016-01-01

    DNA derived from formalin-fixed and paraffin-embedded (FFPE) tissue has been a challenge to large-scale genomic sequencing, due to its low quality and quantities. Improved techniques enabling the genome-wide analysis of FFPE material would be of great value, both from a research and clinical perspective. Comparing a single-strand DNA library preparation method originally developed for ancient DNA to conventional protocols using double-stranded DNA derived from FFPE material we obtain on average 900-fold more library molecules and improved sequence complexity from as little as 5 ng input DNA. FFPE DNA is highly fragmented, usually below 100bp, and up to 60% of reads start after or end prior to adenine residues, suggesting that crosslinks predominate at adenine residues. Similar to ancient DNA, C > T substitutions are slightly increased with maximum rates up to 3% at the ends of molecules. In whole exome sequencing of single-strand libraries from lung, breast, colorectal, prostate and skin cancers we identify known cancer mutations. In summary, we show that single-strand library preparation enables genomic sequencing, even from low amounts of degraded FFPE DNA. This method provides a clear advantage both in research and clinical settings, where FFPE material (e.g. from biopsies) often is the only source of DNA available. Improving the genetic characterization that can be performed on conventional archived FFPE tissue, the single-strand library preparation allows scarce samples to be used in personalized medicine and enables larger sample sizes in future sequencing studies. PMID:27463017

  10. Sphincter-saving surgeries for rectal cancer: A single center study from Kashmir

    PubMed Central

    Mir, Shabeer Ahmed; Chowdri, Nisar A.; Parray, Fazl Q.; Mir, Parvez Ahmed; Bashir, Yasir; Nafae, Muntakhab

    2013-01-01

    Summary and Background Data: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, bladder and sexual function. Surgical resection using sharp mesorectal dissection is important for achieving these goals. Objectives: The current treatment of choice for carcinoma rectum is sphincter saving procedures, which have practically replaced the previously done abdominoperineal resection. We performed a study in our institute to evaluate the surgical outcome and complications of rectal cancer. Materials and Methods: This prospectivestudy included 117 patients, treated for primary rectal cancer by low anterior resection (LAR) from May 2007 to December 2010. All patients underwent standard total mesorectal excision (TME) followed by restoration of continuity. Results: The peri-operative mortality rate was 2.5% (3/117). Post-operative complications occurred in 32% of the patients. After a median follow up of 42 months, local recurrences developed in 6 (5%) patients and distant metastasis in 5 (4.2%). The survival rate was 93%. Conclusion: The concept of total mesorectal excision (TME), advances in stapling technology and neoadjuvant therapy have made it possible to preserve the anal sphincter in most of the patients. Rectal cancer needs to be managed especially in a specialized unit for better results. PMID:24455643

  11. An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis.

    PubMed

    Sunzel, Maria; Learoyd, Maria; Li, Jianguo; Li, Yan; Ngo, Ngoc; Edeki, Timi

    2015-12-01

    For patients with normal renal function, the recommended ceftaroline fosamil dose is a 600 mg 1-h intravenous (i.v.) infusion every 12 h (q12h). In patients with a creatinine clearance of ≤30 mL/min, including those with end-stage renal disease (ESRD), the recommended dose is a 200 mg 1-h i.v. infusion q12h. This phase 1 study (NCT01664065) evaluated the pharmacokinetics, safety and tolerability of ceftaroline fosamil 200 mg 1-h i.v. infusion in patients with ESRD. Patients with ESRD (n=8) participated in two treatment periods (ceftaroline fosamil 200 mg administered pre- and post-haemodialysis) separated by >1 week. Healthy volunteers (n=7) received a single 600 mg dose of ceftaroline fosamil. Blood (pre- and post-haemodialysis) and dialysate samples were obtained for pharmacokinetic analysis. In patients with ESRD, the geometric mean [coefficient of variation (%CV)] plasma ceftaroline area under the plasma concentration-time curve from zero to infinity (AUC0-∞) following post-haemodialysis ceftaroline fosamil 200 mg infusion was 64.8 (38.9)μg·h/mL, similar to that in volunteers following a 600 mg infusion [62.7 (9.4)μg·h/mL]. Ceftaroline AUC0-∞ decreased by ca. 50% when infusion was initiated pre-haemodialysis. In the pre-haemodialysis treatment period, 80% of the ceftaroline fosamil dose was recovered in dialysate as ceftaroline (73%) and ceftaroline M-1 (7%). The frequency of adverse events was similar across patients with ESRD (pre- and post-haemodialysis) and volunteers (43%, 50% and 43% of subjects, respectively). Ceftaroline fosamil 200 mg 1-h i.v. infusion q12h, administered post-haemodialysis on dialysis days, is an appropriate dosage regimen for ESRD patients.

  12. Extraperitoneal versus transperitoneal laparoscopic radical cystectomy for selected elderly bladder cancer patients: a single center experience

    PubMed Central

    Feng, Lang; Song, Jian; Wu, Menghua; Tian, Ye; Zhang, Daoxin

    2016-01-01

    ABSTRACT Objective: This study reports the initial experience of extraperitoneal laparoscopic radical cystectomy (ELRC) and compared with transperitoneal laparoscopic radical cystectomy (TLRC) in the treatment of selected elderly bladder cancer patients. Patients and Methods: A total of forty male bladder cancer patients who underwent ELRC (n=19) or TLRC (n=21) with ureterocutaneostomy were investigated. Demographic parameters, perioperative variables, oncological outcomes and follow-up data were retrospectively analyzed. Results: A significantly shorter time to exsufflation (1.5±0.7 vs 2.1±1.1 d; p=0.026) and liquid intake (1.8±0.9 vs 2.8±1.9 d; p=0.035) were observed in the ELRC group compared with the TLRC group. The incidence of postoperative ileus in the ELRC group was lower than the TLRC group (0 vs 9.5%). However, the difference had no statistical significance (p>0.05). The removed lymph node number in the ELRC group was significantly lower than the TLRC group (p<0.001). No significant differences were observed between the two groups in the overall and cancer-free survival rates (p>0.05). Conclusions: ELRC seems to be a safe and feasible surgical strategy for the selected elderly bladder cancer patients with ≤ T2 disease. The surgical and oncological efficacy of the ELRC is similar to that of the TLRC, but with faster intestinal function recovery. Further studies with a large series including different urinary diversions are needed to confirm our results and to better evaluate the benefit of ELRC in bladder cancer patients. PMID:27564274

  13. Single molecule study of heterotypic interactions between mucins possessing the Tn cancer antigen

    PubMed Central

    Haugstad, Kristin E; Stokke, Bjørn T; Brewer, C Fred; Gerken, Thomas A; Sletmoen, Marit

    2015-01-01

    Mucins are linear, heavily O-glycosylated proteins with physiological roles that include cell signaling, cell adhesion, inflammation, immune response and tumorgenesis. Cancer-associated mucins often differ from normal mucins by presenting truncated carbohydrate chains. Characterization of the binding properties of mucins with truncated carbohydrate side chains could thus prove relevant for understanding their role in cancer mechanisms such as metastasis and recognition by the immune system. In this work, heterotypic interactions of model mucins that possess the Tn (GalNAcαThr/Ser) and T (Galβ1–3GalNAcαThr/Ser) cancer antigens derived from porcine submaxillary mucin (PSM) were studied using atomic force microscopy. PSM possessing only the Tn antigen (Tn-PSM) was found to bind to PSM analogs possessing a combination of T, Tn and STn antigens as well as biosynthetic analogs of the core 1 blood group A tetrasaccharide (GalNAcα1–3[Fucα1–2] Galβ1–3GalNAcαSer/Thr). The rupture forces for the heterotypic interactions ranged from 18– to 31 pN at a force-loading rate of ∼0.5 nN/s. The thermally averaged distance from the bound complex to the transition state (xβ) was estimated to be in the range 0.37–0.87 nm for the first barrier of the Bell Evans analysis and within 0.34–0.64 nm based on a lifetime analysis. These findings reveal that the binding strength and energy landscape for heterotypic interactions of Tn-PSM with the above mucins, resemble homotypic interactions of Tn-PSM. This suggests common carbohydrate epitope interactions for the Tn cancer antigen with the above mucin analogs, a finding that may be important to the role of the Tn antigen in cancer cells. PMID:25527429

  14. Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Randomized Single-Blind Controlled Pilot Study

    PubMed Central

    Trybulski, R.; Kucharzewski, M.; Kucio, C.; Mikusek, W.; Klakla, K.

    2013-01-01

    The aim of the study was to assess the efficacy of Kinesiology Taping (KT) for treating breast cancer-related lymphedema. Sixty-five women with unilateral stage II and III lymphedema were randomly grouped into the KT group (K-tapes, n = 20), the Quasi KT group (quasi K-tapes, n = 22), or the MCT group (multilayered compression therapy group, n = 23). Skin care, 45 min pneumatic compression therapy, 1 h manual lymphatic drainage, and application of K-tape/Quasi K-tapes/multilayered short-stretch bandages were given every treatment session, 3 times per week for 1 month. Patient evaluation items included limb size and percentage edema. Comparing the changes in K-tapes with quasi K-tapes changes, there were no significant differences (P > 0.05). The edema reduction of multilayered bandages was much better than in results observed in taping groups. The KT appeared to be ineffective at secondary lymphedema after breast cancer treatment. The single-blind, controlled pilot study results suggest that K-tape could not replace the bandage, and at this moment it must not be an alternative choice for the breast cancer-related lymphedema patient. The trial is registered with ACTRN12613001173785. PMID:24377096

  15. Effect of Kinesiology Taping on breast cancer-related lymphedema: a randomized single-blind controlled pilot study.

    PubMed

    Smykla, A; Walewicz, K; Trybulski, R; Halski, T; Kucharzewski, M; Kucio, C; Mikusek, W; Klakla, K; Taradaj, J

    2013-01-01

    The aim of the study was to assess the efficacy of Kinesiology Taping (KT) for treating breast cancer-related lymphedema. Sixty-five women with unilateral stage II and III lymphedema were randomly grouped into the KT group (K-tapes, n = 20), the Quasi KT group (quasi K-tapes, n = 22), or the MCT group (multilayered compression therapy group, n = 23). Skin care, 45 min pneumatic compression therapy, 1 h manual lymphatic drainage, and application of K-tape/Quasi K-tapes/multilayered short-stretch bandages were given every treatment session, 3 times per week for 1 month. Patient evaluation items included limb size and percentage edema. Comparing the changes in K-tapes with quasi K-tapes changes, there were no significant differences (P > 0.05). The edema reduction of multilayered bandages was much better than in results observed in taping groups. The KT appeared to be ineffective at secondary lymphedema after breast cancer treatment. The single-blind, controlled pilot study results suggest that K-tape could not replace the bandage, and at this moment it must not be an alternative choice for the breast cancer-related lymphedema patient. The trial is registered with ACTRN12613001173785.

  16. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells

    PubMed Central

    Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-01-01

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway. PMID:27557491

  17. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells.

    PubMed

    Jing, Zhao; Fei, Weiqiang; Zhou, Jichun; Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-09-20

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.

  18. Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging

    PubMed Central

    Gonda, Kohsuke; Miyashita, Minoru; Higuchi, Hideo; Tada, Hiroshi; Watanabe, Tomonobu M.; Watanabe, Mika; Ishida, Takanori; Ohuchi, Noriaki

    2015-01-01

    In breast cancer, the prognosis of human epidermal growth factor receptor 2 (HER2)-positive patients (20–25%) has been dramatically improved by the clinical application of the anti-HER2 antibody drugs trastuzumab and pertuzumab. However, the clinical outcomes of HER2-negative cases with a poor prognosis have not improved, and novel therapeutic antibody drugs or diagnostic molecular markers of prognosis are urgently needed. Here, we targeted protease-activated receptor 1 (PAR1) as a new biomarker for HER2-negative patients. The developed anti-PAR1 antibody inhibited PAR1 activation by matrix metalloprotease 1 and thereby prevented cancer-cell migration and invasion. To estimate PAR1 expression levels in HER2-negative patient tissues using the antibody, user-friendly immunohistochemistry with fluorescence nanoparticles or quantum dots (QDs) was developed. Previously, immunohistochemistry with QDs was affected by tissue autofluorescence, making quantitative measurement extremely difficult. We significantly improved the quantitative sensitivity of immunohistochemistry with QDs by using an autofluorescence-subtracted image and single-QD imaging. The immunohistochemistry showed that PAR1 expression was strongly correlated with relapse-free survival time in HER2-negative breast cancer patients. Therefore, the developed anti-PAR1 antibody is a strong candidate for use as an anticancer drug and a prognostic biomarker for HER2-negative patients. PMID:26392299

  19. Toxicity of Raw and Purified Single-Walled Carbon Nanotubes in Rat's Lung Epithelial and Cervical Cancer Cells.

    PubMed

    Goornavar, Virupaxi; Biradar, Santoshkumar; Ezeagwu, Christian; Ezeagwu, Dexter; Hall, Joseph C; Ramesh, Govindarajan T

    2015-03-01

    The increased applications of carbon nanotubes in the field of drug delivery, bioimaging and biosensors demand nanotubes to be of highest purity, free from metallic impurities and amorphous carbon. All of these sectors require a profound investigation about the toxic effects on human and the environment. Many attempts have been made to purify and surface modify the carbon nanotubes, however a detailed study on the raw and purified material has yet to be conducted. Here we present the toxicity studies of raw and the purified single-walled carbon nanotubes in rat's lung epithelial cell and cervical cancer cells (HeLa). These cells were treated with increasing concentration of 0.5 µg/mL to 50 µg/mL and the various biocompatibility assays were performed. The results showed an increased cell death with purified single-walled carbon nanotubes followed by the depletion of antioxidant levels and activation of the caspase cascade at a rapid rate compared to raw single-walled carbon nanotubes. This suggests that purified single walled carbon nanotubes are more toxic to the cells and exhibit ultra-fine particulate matter like toxicity.

  20. Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment.

    PubMed

    Rana, Suresh; Cheng, Chihyao

    2013-10-01

    The volumetric modulated arc therapy (VMAT) technique, in the form of RapidArc, is widely used to treat prostate cancer. The full-single arc (f-SA) technique in RapidArc planning for prostate cancer treatment provides efficient treatment, but it also delivers a higher radiation dose to the rectum. This study aimed to compare the dosimetric results from the new partial-single arc (p-SA) technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment. In this study, 10 patients with low-risk prostate cancer were selected. For each patient, two sets of RapidArc plans (f-SA and p-SA) were created in the Eclipse treatment planning system. The f-SA plan was created using one full arc, and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors. Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters. The f-SA and p-SA plans showed an average difference of ±1% for the doses to the planning target volume (PTV), and there were no clear differences in dose homogeneity or plan conformity. In comparison to the f-SA technique, the p-SA technique reduced the doses to the rectum by approximately 6.1% to 21.2%, to the bladder by approximately 10.3% to 29.5%, and to the penile bulb by approximately 2.2%. In contrast, the dose to the femoral heads, the integral dose, and the number of monitor units were higher in the p-SA plans by approximately 34.4%, 7.7%, and 9.2%, respectively. In conclusion, it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment. For the same PTV coverage and identical plan optimization parameters, the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.

  1. Are Prenatal Ultrasound Scans Associated with the Autism Phenotype? Follow-Up of a Randomised Controlled Trial

    ERIC Educational Resources Information Center

    Stoch, Yonit K.; Williams, Cori J.; Granich, Joanna; Hunt, Anna M.; Landau, Lou I.; Newnham, John P.; Whitehouse, Andrew J. O.

    2012-01-01

    An existing randomised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype. From 2,834 single pregnancies, 1,415 were selected at random to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy (Intensive) and 1,419 to receive a…

  2. TGFB1 Single Nucleotide Polymorphisms Are Associated With Adverse Quality of Life in Prostate Cancer Patients Treated With Radiotherapy

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Cesaretti, Jamie A.; Atencio, David P.; Peters, Sheila B.A.; Burri, Ryan J.; Stone, Nelson N.; Ostrer, Harry; Rosenstein, Barry S.

    2008-03-01

    Purpose: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. Methods and Materials: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). Results: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). Conclusions: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

  3. Moving to place: childhood cancer treatment decision making in single-parent and repartnered family structures.

    PubMed

    Kelly, Katherine Patterson; Ganong, Lawrence

    2011-03-01

    Few researchers have studied how parents from diverse family structures cope with childhood chronic illness. We designed this study to discern the childhood cancer treatment decision-making (TDM) process in these families. Using grounded theory, we interviewed 15 custodial parents, nonresidential parents, and stepparents who had previously made a major treatment decision for their children with cancer. "Moving to place" was the central psychosocial process by which parents negotiated involvement in TDM. Parents moved toward or were moved away from involvement based on parent position in the family (custodial, nonresidential, and stepparent), prediagnosis family dynamics, and time since diagnosis. Parents used the actions of stepping up, stepping back, being pushed, and stepping away to respond to the need for TDM. Parents faced additional stressors because of their family situations, which affected the TDM process. Findings from this study provide important insight into diverse families and their unique parental TDM experiences.

  4. Intraoperative Radiotherapy for Pancreatic Cancer: 30-Year Experience in a Single Institution in Japan

    SciTech Connect

    Jingu, Keiichi; Tanabe, Takaya; Nemoto, Kenji; Ariga, Hisanori; Umezawa, Rei; Ogawa, Yoshihiro; Takeda, Ken; Koto, Masashi; Sugawara, Toshiyuki; Kubozono, Masaki; Shimizu, Eiji; Abe, Keiko; Yamada, Shogo

    2012-07-15

    Purpose: To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy ({+-} EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. Methods and Materials: Records for 322 patients with pancreatic cancer treated by IORT {+-} EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy were enrolled in the present study. Results: Eighty-three patients underwent gross total resection (R0: 48 patients, R1: 35 patients), and 109 patients underwent only biopsy or palliative resection. Fifty-five patients underwent adjuvant EBRT, and 124 underwent adjuvant chemotherapy. The median doses of IORT and EBRT were 25 and 40 Gy, respectively. The median follow-up period was 37.5 months. At the time of the analysis, 166 patients had disease recurrence, and 35 patients had local failure. The 2-year local control (LC) and overall survival (OS) rates were 71.0% and 16.9%, respectively. Comparison of the results for each decade showed that OS was significantly improved decade by decade (2-year: 25.0% vs. 18.8% vs. 4.2%, p < 0.001). Multivariate analysis showed that degree of resection (R0-1 vs. R2, hazard ratio = 1.97, p = 0.001) and adjuvant chemotherapy (yes vs. no, hazard ratio = 1.54, p = 0.028) had significant impacts on OS. Late gastrointestinal morbidity of Common Terminology Criteria for Adverse Events version 3.0 grade 4 or 5 was observed in four patients. Conclusion: Excellent local control for pancreatic cancer with few cases of severe late toxicity was achieved by using IORT. OS of patients with pancreatic cancer treated by IORT {+-} EBRT improved significantly decade by decade. Multivariate analysis showed that degree of resection and adjuvant chemotherapy had significant impacts on OS.

  5. Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Testicular Cancer: A Single Center Experiences

    PubMed Central

    Nowroozi, Mohamadreza; Ayati, Mohsen; Arbab, Amir; Jamshidian, Hassan; Ghorbani, Hamidreza; Niroomand, Hassan; Taheri Mahmoodi, Mohsen; Amini, Erfan; Salehi, Sohrab; Hakima, Hamid; Fazeli, Farid; Haghdani, Saeid; Ghadian, Alireza

    2015-01-01

    Background: Testicular cancer accounts for about 1 - 1.5% of all malignancies in men. Radical orchiectomy is curative in 75% of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses ≥ 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Objectives: Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center. Patients and Methods: In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center. Results: Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1%), 10 (47.6%) and 3 (14.28%) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8%) had not retrograde ejaculation. Conclusions: PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center. PMID:26539420

  6. A retrospective analysis of survival and prognostic factors of male breast cancer from a single center

    PubMed Central

    2014-01-01

    Background Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. Methods We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients’ OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. Results In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. Conclusions Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease. PMID:24673740

  7. Sub-cellular force microscopy in single normal and cancer cells

    SciTech Connect

    Babahosseini, H.; Carmichael, B.; Strobl, J.S.; Mahmoodi, S.N.; Agah, M.

    2015-08-07

    This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain.

  8. Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress

    PubMed Central

    Du, Zhanwen; Gao, Jinnan; Yang, Shuming; Gorityala, Shashank; Xiong, Xiahui; Deng, Ou; Ma, Zhefu; Yan, Chunhong; Susana, Gonzalo; Xu, Yan; Zhang, Junran

    2016-01-01

    Radiotherapy (RT) remains a standard therapeutic modality for breast cancer patients. However, intrinsic or acquired resistance limits the efficacy of RT. Here, we demonstrate that CHK1 inhibitor AZD7762 alone significantly inhibited the growth of radioresistant breast cancer cells (RBCC). Given the critical role of ATR/CHK1 signaling in suppressing oncogene-induced replication stress (RS), we hypothesize that CHK1 inhibition leads to the specific killing for RBCC due to its abrogation in the suppression of RS induced by oncogenes. In agreement, the expression of oncogenes c-Myc/CDC25A/c-Src/H-ras/E2F1 and DNA damage response (DDR) proteins ATR/CHK1/BRCA1/CtIP were elevated in RBCC. AZD7762 exposure led to significantly higher levels of RS in RBCC, compared to the parental cells. The mechanisms by which CHK1 inhibition led to specific increase of RS in RBCC were related to the interruptions in the replication fork dynamics and the homologous recombination (HR). In summary, RBCC activate oncogenic pathways and thus depend upon mechanisms controlled by CHK1 signaling to maintain RS under control for survival. Our study provided the first example where upregulating RS by CHK1 inhibitor contributes to the specific killing of RBCC, and highlight the importance of the CHK1 as a potential target for treatment of radioresistant cancer cells. PMID:27167194

  9. An Intervention Study on Screening for Breast Cancer Among Single African-American Women Aged 65 and Older

    DTIC Science & Technology

    2000-07-01

    Improving the use of cancer screening for older women. Cancer 1993;72:1084-7. 2. Dewar MA, Hall K, Perchalski J. Cervical cancer screening: past...Brackbill RM, Bewerse BA, Sanderson LM. Cancer screening behaviors among U.S. women: breast cancer, 1987-1989, and cervical cancer , 1988-1989. MMWR...A nurse practionner intervention to increase breast and cervical cancer screening for poor, elderly black women. J Gen Intern Med 1993;8:173- 8. 31

  10. Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

    PubMed Central

    White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

    2016-01-01

    Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for

  11. Surgery for Type B Ankle Fracture Treatment: a Combined Randomised and Observational Study (CROSSBAT)

    PubMed Central

    Harris, Ian A; Naylor, Justine M

    2017-01-01

    Background Isolated type B ankle fractures with no injury to the medial side are the most common type of ankle fracture. Objective This study aimed to determine if surgery is superior to non-surgical management for the treatment of these fractures. Methods A pragmatic, multicentre, single-blinded, combined randomised controlled trial and observational study. Setting Participants between 18 and 65 years with a type B ankle fracture and minimal talar shift were recruited from 22 hospitals in Australia and New Zealand. Participants willing to be randomised were randomly allocated to undergo surgical fixation followed by mobilisation in a walking boot for 6 weeks. Those treated non-surgically were managed in a walking boot for 6 weeks. Participants not willing to be randomised formed the observational cohort. Randomisation stratified by site and using permuted variable blocks was administered centrally. Outcome assessors were blinded for the primary outcomes. Primary outcomes Patient-reported ankle function using the American Academy of Orthopaedic Surgeons Foot and Ankle Outcomes Questionnaire (FAOQ) and the physical component score (PCS) of the SF-12v2 General Health Survey at 12 months postinjury. Primary analysis was intention to treat; the randomised and observational cohorts were analysed separately. Results From August 2010 to October 2013, 160 people were randomised (80 surgical and 80 non-surgical); 139 (71 surgical and 68 non-surgical) were analysed as intention to treat. 276 formed the observational cohort (19 surgical and 257 non-surgical); 220 (18 surgical and 202 non-surgical) were analysed. The randomised cohort demonstrated that surgery was not superior to non-surgery for the FAOQ (49.8 vs 53.0; mean difference 3.2 (95% CI 0.4 to 5.9), p=0.028), or the PCS (53.7 vs 53.2; mean difference 0.6 (−2.9 to 1.8), p=0.63). 23 (32%) and 10 (14%) participants had an adverse event in the surgical and non-surgical groups, respectively. Similar results were

  12. Significance of a single CA 125 assay combined with ultrasound in the early detection of ovarian and endometrial cancer.

    PubMed

    Vuento, M H; Stenman, U H; Pirhonen, J P; Mäkinen, J I; Laippala, P J; Salmi, T A

    1997-01-01

    We evaluated the utility of a single CA 125 measurement in combination with transvaginal sonography for early detection of ovarian and endometrial cancer in asymptomatic postmenopausal women. A sample of peripheral blood was taken from 1291 apparently healthy postmenopausal women, who were examined by conventional and color Doppler ultrasound for early detection of ovarian and endometrial cancer. Serum CA 125 was determined in all samples 3 years later by the IMx CA 125 assay (Abbott Laboratories, Abbott Park, IL). The cutoff level based on the 99th percentile was 30 U/ml. Elevated values were controlled by repeat sonography and an additional determination of CA 125. Record linkage with the files of the Finnish Cancer Registry was performed 3 1/2 years after the primary sonographic screening. The mean CA 125 concentration was 8.1 U/ml (range 0-1410 U/ml). Fourteen of the 1291 women had a CA 125 level greater than 30 U/ml. None of these had signs of either endometrial or ovarian malignancy in the primary sonography screening. Among the other women three cases of endometrial carcinoma (all stage Ib) and one ovarian carcinoma (stage Ia with borderline malignancy) were detected by sonography. All these patients had a CA 125 value <30 U/ml, the mean value being 11.4 U/ml (range 7.5-16.7 U/ml). During follow-up of 3.5 years, one stage Ia ovarian carcinoma, one abdominal carcinomatosis, and two endometrial carcinomas (both stage Ib) were diagnosed. In these patients the mean value for CA 125 was 12.7 U/ml (range 2.5-30.9 U/ml) at the primary sonography screening. A single CA 125 measurement provides no advantage in the early detection of ovarian and endometrial cancer in asymptomatic postmenopausal women compared with transvaginal sonography. The vast majority of women with an elevated CA 125 value have some reason other than an ovarian or endometrial malignancy for this finding.

  13. Rehabilitation Enablement in Chronic Heart Failure—a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers: rationale and protocol for a single-centre pilot randomised controlled trial

    PubMed Central

    Lang, C C; Smith, K; Jolly, K; Davis, R; Hayward, C; Wingham, J; Abraham, C; Green, C; Warren, F C; Britten, N; Greaves, C J; Doherty, P; Austin, J; Van Lingen, R; Singh, S; Buckingham, S; Paul, K; Taylor, R S; Dalal, H M

    2016-01-01

    Introduction The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. Methods and analysis A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. Ethics and dissemination The study is approved by the East of Scotland Research Ethics

  14. Treatment of Common Bile Duct Obstruction by Pancreatic Cancer Using Various Stents: Single-Center Experience

    SciTech Connect

    Nakamura, Toshifumi; Hirai, Ritsuko; Kitagawa, Mutsuo; Takehira, Yasunori; Yamada, Masami; Tamakoshi, Katsutoshi; Kobayashi, Yoshimasa; Nakamura, Hirotoshi; Kanamori, Masao

    2002-10-15

    Purpose: To compare the effectiveness of various means of stenting in patients with biliary obstruction caused by pancreatic cancer in a retrospective analysis. Methods: Sixty-two patients with biliary obstruction due to unresectable pancreatic cancer underwent biliary stenting. On the basis of the findings obtained by percutaneous transhepatic cholangiography(10 patients) and endoscopic retrograde cholangiography (52 patients),the site of obstruction was distal to the hilar confluence,predominantly especially in the middle to lower third of the common bile duct. Polyurethane-covered Wallstents (9 mm in diameter) we reinserted in 13 patients, while uncovered Wallstents (10 mm in diameter)were used in 10 patients and plastic stents (10 Fr and 12 Fr) were used in 39 patients. Results: Stenting was successful in 34 patients (87.2%) treated with plastic stents and in 22 patients(95.7%) treated with Wallstents. Effective biliary drainage was achieved in 32 out of 34 patients (94.1%) treated with plastic stents and in 21 out of 22 patients (95.5%) treated with Wallstents. The cumulative patency rate was significantly higher for the uncovered and covered Wallstents compared to plastic stents, but was not significantly higher for covered than for uncovered Wallstents. Stentocclusion occurred in 23 patients (70%; all by clogging) from the plastic stent group, in two patients (22%; by tumor ingrowth) from the uncovered Wallstent group, and in one patient (9%; by clogging) from the covered Wallstent group. The survival rate showed no significant difference among the three stent groups. Conclusion: The Wallstent is effective for long-term palliation in patients with obstruction caused by pancreatic cancer invading the middle to lower part of the common bile duct. The covered Wallstent can prevent tumor ingrowth, a problem with the uncovered Wallstent. However, it may be necessary to take measures to prevent the migration or clogging of covered Wallstents.

  15. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial

    PubMed Central

    Davies, Christina; Pan, Hongchao; Godwin, Jon; Gray, Richard; Arriagada, Rodrigo; Raina, Vinod; Abraham, Mirta; Alencar, Victor Hugo Medeiros; Badran, Atef; Bonfill, Xavier; Bradbury, Joan; Clarke, Michael; Collins, Rory; Davis, Susan R; Delmestri, Antonella; Forbes, John F; Haddad, Peiman; Hou, Ming-Feng; Inbar, Moshe; Khaled, Hussein; Kielanowska, Joanna; Kwan, Wing-Hong; Mathew, Beela S; Müller, Bettina; Nicolucci, Antonio; Peralta, Octavio; Pernas, Fany; Petruzelka, Lubos; Pienkowski, Tadeusz; Rajan, Balakrishnan; Rubach, Maryna T; Tort, Sera; Urrútia, Gerard; Valentini, Miriam; Wang, Yaochen; Peto, Richard

    2013-01-01

    Summary Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality

  16. HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor.

    PubMed

    Ben-Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M; Ma, Cynthia X; Ellis, Matthew J

    2015-09-01

    Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient's functional status. This partial response lasted 11 months, and when the patient's cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2-mutated solid tumors is warranted.

  17. Mesoscopic modeling of cancer photothermal therapy using single-walled carbon nanotubes and near infrared radiation: insights through an off-lattice Monte Carlo approach

    NASA Astrophysics Data System (ADS)

    Gong, Feng; Hongyan, Zhang; Papavassiliou, Dimitrios V.; Bui, Khoa; Lim, Christina; Duong, Hai M.

    2014-05-01

    Single-walled carbon nanotubes (SWNTs) are promising heating agents in cancer photothermal therapy when under near infrared radiation, yet few efforts have been focused on the quantitative understanding of the photothermal energy conversion in biological systems. In this article, a mesoscopic study that takes into account SWNT morphologies (diameter and aspect ratio) and dispersions (orientation and concentration), as well as thermal boundary resistance, is performed by means of an off-lattice Monte Carlo simulation. Results indicate that SWNTs with orientation perpendicular to the laser, smaller diameter and better dispersion have higher heating efficiency in cancer photothermal therapy. Thermal boundary resistances greatly inhibit thermal energy transfer away from SWNTs, thereby affecting their heating efficiency. Through appropriate interfacial modification around SWNTs, compared to the surrounding healthy tissue, a higher temperature of the cancer cell can be achieved, resulting in more effective cancer photothermal therapy. These findings promise to bridge the gap between macroscopic and microscopic computational studies of cancer photothermal therapy.

  18. Robotic surgery of locally advanced gastric cancer: a single-surgeon experience of 41 cases.

    PubMed

    Vasilescu, C; Procopiuc, L

    2012-01-01

    The mainstay of curative gastric cancer treatment is open gastric resection with regional lymph node dissection. Minimally invasive surgery is yet to become an established technique with a well defined role. Robotic surgery has by-passed some of the limitations of conventional laparoscopy and has proven both safe and feasible. We present our initial experience with robotic surgery based on 41 gastric cancer patients. We especially wish to underline the advantages of the robotic system when performing the digestive tract anastomoses. We present the techniques of end-to-side eso-jejunoanastomoses (using a circular stapler or manual suture) and side-to-side eso-jejunoanastomoses. In our hands, the results with circular stapled anastomoses were good and we advocate against manual suturing when performing anastomoses in robotic surgery. Moreover, we recommend performing totally intracorporeal anastomoses which have a better post-operative outcome, especially in obese patients. We present three methods of realising the total intracorporeal eso-jejuno-anastomosis with a circular stapler: manual purse-string suture, using the OrVil and the double stapling technique. The eso-jejunoanastomosis is one of the most difficult steps in performing the total gastrectomy, but these techniques allow the surgeon to choose the best option for each case. We consider that surgeons who undertake total gastrectomies must have a special training in performing these anastomoses.

  19. Sub-cellular force microscopy in single normal and cancer cells.

    PubMed

    Babahosseini, H; Carmichael, B; Strobl, J S; Mahmoodi, S N; Agah, M

    2015-08-07

    This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures.

  20. Vinorelbine with or without Trastuzumab in Metastatic Breast Cancer: A Retrospective Single Institution Series

    PubMed Central

    Stravodimou, Athina; Zaman, Khalil; Voutsadakis, Ioannis A.

    2014-01-01

    Background. We report our experience with vinorelbine, a widely used chemotherapeutic, in unselected metastatic breast cancer patients treated in clinical routine. Patients and Methods. The data of all patients with metastatic breast cancer receiving vinorelbine with or without trastuzumab during a six year period were reviewed. Patients received vinorelbine intravenous 25–30 mg/m2 or 60–80 mg/m2 orally in days 1 and 8 of a 21 day cycle. Results. Eighty-seven women were included. Sixty-two patients received vinorelbine alone and 25 patients received vinorelbine in combination with trastuzumab. In 67 patients this was the first line treatment for metastatic disease and in 20 patients it was 2nd or later line of treatment. The median TTP was six months (range: 1–45). The median overall survival was 11.5 months (range: 1–83). Seventy patients were evaluable for response. In patients receiving first line treatment 44.4% had a response while in the second and subsequent lines setting 12.5% of patients responded (P = 0.001). Objective response was obtained in 63.6% of patients receiving concomitant trastuzumab and in 25% of patients receiving vinorelbine alone (P = 0.0002). Conclusion. This study confirms a high disease control rate. Response rate and TTP were superior in first line treatment compared to subsequent lines. PMID:25006504

  1. Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway.

    PubMed

    Li, Senpeng; Zhang, Shuo; Jin, Xing; Tan, Xuejie; Lou, Jianfang; Zhang, Xiumei; Zhao, Yunxue

    2014-10-30

    Silver complexes have been shown to possess antimicrobial and anticancer properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, was synthesized in our previous study. In this study, we offer evidence that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis was associated with the levels of intracellular ROS. The further study revealed that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the caspase-3 activation and led to the translocation of apoptosis inducing factor and endonucleaseG to the nucleus. These findings have important implications for the development of silver complexes for anticancer applications.

  2. Graphene oxide-encoded Ag nanoshells with single-particle detection sensitivity towards cancer cell imaging based on SERRS.

    PubMed

    Yim, DaBin; Kang, Homan; Jeon, Su-Ji; Kim, Hye-In; Yang, Jin-Kyoung; Kang, Tae Wook; Lee, Sangyeop; Choo, Jaebum; Lee, Yoon-Sik; Kim, Jin Woong; Kim, Jong-Ho

    2015-05-21

    Developing ultrasensitive Raman nanoprobes is one of the emerging interests in the field of biosensing and bioimaging. Herein, we constructed a new type of surface-enhanced resonance Raman scattering nanoprobe composed of an Ag nanoshell as a surface-enhanced Raman scattering-active nanostructure, which was encapsulated with 4,7,10-trioxa-1,13-tridecanediamine-functionalized graphene oxide as an ultrasensitive Raman reporter exhibiting strong resonance Raman scattering including distinct D and G modes. The designed nanoprobe was able to produce much more intense and simpler Raman signals even at a single particle level than the Ag nanoshell bearing a well-known Raman reporter, which is beneficial for the sensitive detection of a target in a complex biological system. Finally, this ultrasensitive nanoprobe successfully demonstrated its potential for bioimaging of cancer cells using Raman spectroscopy.

  3. Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data

    PubMed Central

    Zhang, Bo; Liu, Dajiang J.; Muscat, Joshua E.; Langan, Sara T.; Connor, James R.

    2017-01-01

    Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119–0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474–0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients’ survival in the TCGA data set of GBM. PMID:28358914

  4. Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

    PubMed Central

    ZHAO, YA-NAN; HE, DONG-NING; WANG, YA-DI; LI, JUN-JIE; HA, MIN-WEN

    2016-01-01

    The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method. PMID:27073578

  5. Patient-Specific Quality Assurance for Prostate Cancer Patients Receiving Spot Scanning Proton Therapy Using Single-Field Uniform Dose

    SciTech Connect

    Zhu, X. Ronald; Poenisch, Falk; Song, Xiaofei; Johnson, Jennifer L.; Ciangaru, George; Taylor, M. Brad; Lii, Ming Fwu; Martin, Craig; Arjomandy, Bijan; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh nhu; Gillin, Michael T.; Sahoo, Narayan

    2011-10-01

    Purpose: To describe our experiences with patient-specific quality assurance (QA) for patients with prostate cancer receiving spot scanning proton therapy (SSPT) using single-field uniform dose (SFUD). Methods and Materials: The first group of 249 patients with prostate cancer treated with SSPT using SFUD was included in this work. The scanning-beam planning target volume and number of monitor units were recorded and checked for consistency. Patient-specific dosimetric measurements were performed, including the point dose for each plan, depth doses, and two-dimensional (2D) dose distribution in the planes perpendicular to the incident beam direction for each field at multiple depths. The {gamma}-index with 3% dose or 3-mm distance agreement criteria was used to evaluate the 2D dose distributions. Results: We observed a linear relationship between the number of monitor units and scanning-beam planning target volume. The difference between the measured and calculated point doses (mean {+-} SD) was 0.0% {+-} 0.7% (range, -2.9% to 1.8%). In general, the depth doses exhibited good agreement except at the distal end of the spread-out Bragg peak. The pass rate of {gamma}-index (mean {+-} SD) for 2D dose comparison was 96.2% {+-} 2.6% (range, 90-100%). Discrepancies between the measured and calculated dose distributions primarily resulted from the limitation of the model used by the treatment planning system. Conclusions: We have established a patient-specific QA program for prostate cancer patients receiving SSPT using SFUD.

  6. Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer.

    PubMed

    Trejo-de la O, A; Hernández-Sancén, P; Maldonado-Bernal, C

    2014-04-01

    Innate and adaptive immune responses in humans have evolved as protective mechanisms against infectious microorganisms. Toll-like receptors (TLRs) have an important role in the recognition of invading microorganisms. TLRs are the first receptors to detect potential pathogens and to initiate the immune response, and they form the crucial link between the innate and adaptive immune responses. TLRs also have an important role in the pathophysiology of infectious and inflammatory diseases. Increasing data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single-nucleotide polymorphisms (SNPs) within TLR genes, resulting in an altered susceptibility to infectious or inflammatory disease that might contribute to the pathogenesis of complex diseases such as cancer. The associations between diseases and SNPs are in the early stage of discovery. Important clinical insights are emerging, and these polymorphisms provide new understanding of common diseases. This review summarizes and discusses the studies that shed light on the relevance of these polymorphisms in human infectious and inflammatory diseases and cancer.

  7. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain

    PubMed Central

    Coluccio, Maria Laura; Gentile, Francesco; Das, Gobind; Nicastri, Annalisa; Perri, Angela Mena; Candeloro, Patrizio; Perozziello, Gerardo; Proietti Zaccaria, Remo; Gongora, Juan Sebastian Totero; Alrasheed, Salma; Fratalocchi, Andrea; Limongi, Tania; Cuda, Giovanni; Di Fabrizio, Enzo

    2015-01-01

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10−12 M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components. PMID:26601267

  8. EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion.

    PubMed

    Sugiyama, Nami; Gucciardo, Erika; Tatti, Olga; Varjosalo, Markku; Hyytiäinen, Marko; Gstaiger, Matthias; Lehti, Kaisa

    2013-04-29

    Changes in EphA2 signaling can affect cancer cell-cell communication and motility through effects on actomyosin contractility. However, the underlying cell-surface interactions and molecular mechanisms of how EphA2 mediates these effects have remained unclear. We demonstrate here that EphA2 and membrane-anchored membrane type-1 matrix metalloproteinase (MT1-MMP) were selectively up-regulated and coexpressed in invasive breast carcinoma cells, where, upon physical interaction in same cell-surface complexes, MT1-MMP cleaved EphA2 at its Fibronectin type-III domain 1. This cleavage, coupled with EphA2-dependent Src activation, triggered intracellular EphA2 translocation, as well as an increase in RhoA activity and cell junction disassembly, which suggests an overall repulsive effect between cells. Consistent with this, cleavage-prone EphA2-D359I mutant shifted breast carcinoma cell invasion from collective to rounded single-cell invasion within collagen and in vivo. Up-regulated MT1-MMP also codistributed with intracellular EphA2 in invasive cells within human breast carcinomas. These results reveal a new proteolytic regulatory mechanism of cell-cell signaling in cancer invasion.

  9. EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion

    PubMed Central

    Sugiyama, Nami; Gucciardo, Erika; Tatti, Olga; Varjosalo, Markku; Hyytiäinen, Marko; Gstaiger, Matthias

    2013-01-01

    Changes in EphA2 signaling can affect cancer cell–cell communication and motility through effects on actomyosin contractility. However, the underlying cell–surface interactions and molecular mechanisms of how EphA2 mediates these effects have remained unclear. We demonstrate here that EphA2 and membrane-anchored membrane type-1 matrix metalloproteinase (MT1-MMP) were selectively up-regulated and coexpressed in invasive breast carcinoma cells, where, upon physical interaction in same cell–surface complexes, MT1-MMP cleaved EphA2 at its Fibronectin type-III domain 1. This cleavage, coupled with EphA2-dependent Src activation, triggered intracellular EphA2 translocation, as well as an increase in RhoA activity and cell junction disassembly, which suggests an overall repulsive effect between cells. Consistent with this, cleavage-prone EphA2-D359I mutant shifted breast carcinoma cell invasion from collective to rounded single-cell invasion within collagen and in vivo. Up-regulated MT1-MMP also codistributed with intracellular EphA2 in invasive cells within human breast carcinomas. These results reveal a new proteolytic regulatory mechanism of cell–cell signaling in cancer invasion. PMID:23629968

  10. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    SciTech Connect

    Filippi, Andrea Riccardo; Badellino, Serena; Ceccarelli, Manuela; Guarneri, Alessia; Franco, Pierfrancesco; Monagheddu, Chiara; Spadi, Rosella; Ragona, Riccardo; Racca, Patrizia; Ricardi, Umberto

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  11. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain.

    PubMed

    Coluccio, Maria Laura; Gentile, Francesco; Das, Gobind; Nicastri, Annalisa; Perri, Angela Mena; Candeloro, Patrizio; Perozziello, Gerardo; Proietti Zaccaria, Remo; Gongora, Juan Sebastian Totero; Alrasheed, Salma; Fratalocchi, Andrea; Limongi, Tania; Cuda, Giovanni; Di Fabrizio, Enzo

    2015-09-01

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10(-12) M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components.

  12. Historical controls for metastatic pancreatic cancer: benchmarks for planning and analyzing single-arm phase II trials.

    PubMed

    Philip, Philip A; Chansky, Kari; LeBlanc, Michael; Rubinstein, Lawrence; Seymour, Lesley; Ivy, S Percy; Alberts, Steven R; Catalano, Paul J; Crowley, John

    2014-08-15

    We compiled and analyzed a database of cooperative group trials in advanced pancreatic cancer to develop historical benchmarks for overall survival (OS) and progression-free survival (PFS). Such benchmarks are essential for evaluating new therapies in a single-arm setting. The analysis included patients with untreated metastatic pancreatic cancer receiving regimens that included gemcitabine, between 1995 and 2005. Prognostic baseline factors were selected by their significance in Cox regression analysis. Outlier trial arms were identified by comparing individual 6-month OS and PFS rates against the entire group. The dataset selected for the generation of OS and PFS benchmarks was then tested for intertrial arm variability using a logistic-normal model with the selected baseline prognostic factors as fixed effects and the individual trial arm as a random effect. A total of 1,132 cases from eight trials qualified. Performance status and sex were independently significant for OS, and performance status was prognostic for PFS. Outcomes for one trial (NCCTG-034A) were significantly different from the other trial arms. When this trial was excluded, the remaining trial arms were homogeneous for OS and PFS outcomes after adjusting for performance status and sex. Benchmark values for 6-month OS and PFS are reported along with a method for using these values in future study design and analysis. The benchmark survival values were generated from a dataset that was homogeneous between trials. The benchmarks can be used to enable single-arm phase II trials using a gemcitabine platform, especially under certain circumstances. Such circumstances might be when a randomized control arm is not practically feasible, an early signal of activity of an experimental agent is being explored such as in expansion cohorts of phase I studies, and in patients who are not candidates for combination cytotoxic therapy.

  13. A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes

    NASA Astrophysics Data System (ADS)

    Lamprecht, C.; Plochberger, B.; Ruprecht, V.; Wieser, S.; Rankl, C.; Heister, E.; Unterauer, B.; Brameshuber, M.; Danzberger, J.; Lukanov, P.; Flahaut, E.; Schütz, G.; Hinterdorfer, P.; Ebner, A.

    2014-03-01

    In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors