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Sample records for cancer randomised single

  1. 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quantitative overview using updated individual patient data from all available randomised trials (published and unpublished).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

  2. Treatment of metastatic and recurrent cervix cancer with chemotherapy: a randomised trial comparing hydroxyurea with cisdiamminedichloro-platinum plus methotrexate.

    PubMed

    Bezwoda, W R; Nissenbaum, M; Derman, D P

    1986-01-01

    In a randomised trial comparing single-agent chemotherapy (hydroxyurea) to combination chemotherapy in advanced cervix cancer, response was seen in 57% (including 13% CR) of patients receiving the combination (DDP + MTX) regimen. Responding patients survived significantly longer (11 months) than either those receiving hydroxyurea or those not responding to combination chemotherapy (4 months). Two patients remain in complete remission for 14+ and 17+ months.

  3. 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

  4. Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

    PubMed

    Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

    2016-08-01

    A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen. PMID:27400912

  5. Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review

    PubMed Central

    Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

    2015-01-01

    Objectives We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. Participants Men and women from 30 to 74 years of age. Setting Randomised trials on cancer screening. Design For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. Main outcome measures Relative risk of cancer death. Results In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. Conclusions The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID:26152677

  6. Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery.

    PubMed

    Jenkins, C D; McDonnell, P J; Spalton, D J

    1990-12-01

    Comparatively little attention has been paid to the conjunctival toxicity of antibiotics administered at the time of cataract surgery. We have observed the effect of subconjunctival gentamicin and cefuroxime injection, using colour photography in a randomised single blind trial of 121 patients undergoing routine cataract surgery. Our results suggest that a hyperaemic eye is likely to occur about twice as often in patients injected with gentamicin (p less than 0.001). Gentamicin is associated with more pain postoperatively (p less than 0.05). Significant manifestations of gentamicin toxicity are conjunctival oedema and capillary closure. Cefuroxime has some theoretical advantages over gentamicin in its antibacterial spectrum.

  7. Single port/incision laparoscopic surgery compared with standard three-port laparoscopic surgery for appendicectomy - a randomised controlled trial

    PubMed Central

    2012-01-01

    Background Laparoscopic surgery has become the preferred approach for many procedures because of reduced post-operative pain, better recovery, shorter hospital stay and improved cosmesis. Single incision laparoscopic surgery is one of the many recent variants where either standard ports or a specially designed single multi-channel port is introduced through a single skin incision. While the cosmetic advantage of this is obvious, the evidence base for claims of reduced morbidity and better post-operative recovery is weak. This study aims to compare the effectiveness of single port/incision laparoscopic appendicectomy with standard three-port laparoscopic appendicectomy in adult patients at six weeks post-surgery. We also wish to assess the feasibility of a multicentre randomised controlled trial comparing single port/incision laparoscopic surgery with standard three-port laparoscopic surgery for other surgical techniques. Methods and design Patients diagnosed with suspected appendicitis and requiring surgical treatment will be randomised to receive either standard three-port or single incision laparoscopic surgery. Data will be collected from clinical notes, operation notes and patient reported questionnaires. The following outcomes will be considered: 1. Effectiveness of the surgical procedure in terms of: •patient reported outcomes •clinical outcomes •resource use 2. Feasibility of conducting a randomised controlled trial (RCT) in the emergency surgical setting by quantifying: •patient eligibility •randomisation acceptability •feasibility of blinding participants to the intervention received •completion rates of case report forms and patient reported questionnaires Trial registration ISRCTN66443895 (assigned 10 March 2011, first patient randomised 09 January 2011) PMID:23111090

  8. Single fatherhood due to cancer.

    PubMed

    Yopp, Justin M; Rosenstein, Donald L

    2012-12-01

    Cancer is a leading cause of widowed fatherhood in the USA. Fathers whose spouses have died from cancer constitute a potentially vulnerable population as they adjust to their role as sole or primary caregiver while managing their own grief and that of their children. The importance of addressing the psychological needs of widowed fathers is underscored by data showing that father's coping and emotional availability are closely tied to their bereaved children's mental health. Surprisingly, scant attention has been given to the phenomenon of widowed fatherhood with virtually no clinical resources or research studies devoted to fathers who have lost their wives to cancer. This commentary highlights key challenges facing this underserved population of widowers and calls for development of research agendas and clinical interventions for single fathers due to cancer.

  9. Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial

    PubMed Central

    2010-01-01

    Background Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave. Methods/Design The Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term) and after 9 months (long term). Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List) and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey), impact on functioning and autonomy (Impact on functioning and autonomy questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), physical fitness (aerobic peak capacity, muscle strength), body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level will be measured

  10. Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials.

    PubMed

    Zikos, Efstathios; Ghislain, Irina; Coens, Corneel; Ediebah, Divine E; Sloan, Elizabeth; Quinten, Chantal; Koller, Michael; van Meerbeeck, Jan P; Flechtner, Hans-Henning; Stupp, Roger; Pallis, Athanasios; Czimbalmos, Agnes; Sprangers, Mirjam A G; Bottomley, Andrew

    2014-02-01

    Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

  11. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer

    PubMed Central

    Conroy, T; Yataghène, Y; Etienne, P L; Michel, P; Senellart, H; Raoul, J L; Mineur, L; Rives, M; Mirabel, X; Lamezec, B; Rio, E; Le Prisé, E; Peiffert, D; Adenis, A

    2010-01-01

    Background: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. Methods: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. Results: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82% arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. Conclusion: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial. PMID:20940718

  12. 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

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

    PubMed

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

    2015-10-01

    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

  14. 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

  15. 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

  16. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

    PubMed Central

    2009-01-01

    Summary Background Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings After a median follow-up of 37 months (IQR 24–58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1·16 (95% CI 0·87–1·54; p=0·31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI −4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1·35 (1·06–1·73; p=0·017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1–12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1·04 (0·74–1·45; p=0·83) and for recurrence-free survival was 1·25 (0·93–1·66; p=0·14). Interpretation Our results show no evidence of benefit in terms of overall

  17. 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

  18. Comparing patients' and clinicians' assessment of outcomes in a randomised trial of sentinel node biopsy for breast cancer (the RACS SNAC trial).

    PubMed

    Smith, Michaella J; Gill, P Grantley; Wetzig, Neil; Sourjina, Tatiana; Gebski, Val; Ung, Owen; Campbell, Ian; Kollias, James; Coskinas, Xanthi; Macphee, Avis; Young, Leonie; Simes, R John; Stockler, Martin R

    2009-09-01

    The RACS sentinel node biopsy versus axillary clearance (SNAC) trial compared sentinel-node-based management (SNBM) and axillary lymph-node dissection (ALND) for breast cancer. In this sub study, we sought to determine whether patient ratings of arm swelling, symptoms, function and disability or clinicians' measurements were most efficient at detecting differences between randomized groups, and therefore, which of these outcome measures would minimise the required sample sizes in future clinical trials. 324 women randomised to SNBM and 319 randomised to ALND were included. The primary endpoint of the trial was percentage increase in arm volume calculated from clinicians' measurements of arm circumference at 10 cm intervals. Secondary endpoints included reductions in range of motion and sensation (both measured by clinicians); and, patients' ratings of arm swelling, symptoms and quality of life, using the European Organisation for Research and Treatment of Cancer Breast Cancer Module (EORTC QLM-BR23), the body image after breast cancer questionnaire (BIBC) and the SNAC study specific scales (SSSS). The relative efficiency (RE, the squared ratio of the test statistics, with 95% confidence intervals calculated by bootstrapping) was used to compare these measures in detecting differences between the treatment groups. Patients' self-ratings of arm swelling were generally more efficient than clinicians' measurements of arm volume in detecting differences between treatment groups. The SSSS arm symptoms scale was the most efficient (RE = 7.1) The entire SSSS was slightly less so (RE = 4.6). Patients' ratings on single items were 3-5 times more efficient than clinicians' measurements. Primary endpoints based on patient-rated outcome measures could reduce the required sample size in future surgical trials.

  19. Evaluating holistic needs assessment in outpatient cancer care—a randomised controlled trial: the study protocol

    PubMed Central

    Snowden, Austyn; Young, Jenny; White, Craig; Murray, Esther; Richard, Claude; Lussier, Marie-Therese; MacArthur, Ewan; Storey, Dawn; Schipani, Stefano; Wheatley, Duncan; McMahon, Jeremy; Ross, Elaine

    2015-01-01

    Introduction People living with and beyond cancer are vulnerable to a number of physical, functional and psychological issues. Undertaking a holistic needs assessment (HNA) is one way to support a structured discussion of patients’ needs within a clinical consultation. However, there is little evidence on how HNA impacts on the dynamics of the clinical consultation. This study aims to establish (1) how HNA affects the type of conversation that goes on during a clinical consultation and (2) how these putative changes impact on shared decision-making and self-efficacy. Methods and analysis The study is hosted by 10 outpatient oncology clinics in the West of Scotland and South West England. Participants are patients with a diagnosis of head and neck, breast, urological, gynaecological and colorectal cancer who have received treatment for their cancer. Patients are randomised to an intervention or control group. The control group entails standard care—routine consultation between the patient and clinician. In the intervention group, the patient completes a holistic needs assessment prior to consultation. The completed assessment is then given to the clinician where it informs a discussion based on the patient's needs and concerns as identified by them. The primary outcome measure is patient participation, as determined by dialogue ratio (DR) and preponderance of initiative (PI) within the consultation. The secondary outcome measures are shared decision-making and self-efficacy. It is hypothesised that HNA will be associated with greater patient participation within the consultation, and that shared decision-making and feelings of self-efficacy will increase as a function of the intervention. Ethics and dissemination This study has been given a favourable opinion by the West of Scotland Research Ethics Committee and NHS Research & Development. Study findings will be disseminated through peer-reviewed publications and conference attendance. Trail registration number

  20. A single blinded randomised controlled pilot trial of prism adaptation for improving self-care in stroke patients with neglect.

    PubMed

    Turton, Ailie J; O'Leary, Kelly; Gabb, Judith; Woodward, Rebecca; Gilchrist, Iain D

    2010-04-01

    Prism adaptation has been shown to alleviate the symptoms of unilateral spatial neglect following stroke in single case and small group studies. The purposes of this single blinded pilot randomised controlled trial were to determine the feasibility of delivering prism adaptation treatment in a clinically valid sample and to assess its impact on self-care. Thirty seven right hemisphere stroke patients with unilateral spatial neglect were randomised into either prism adaptation (using 10 dioptre, 6 degree prisms) or sham treatment (using plain glasses) groups. Treatment was delivered each weekday for two weeks. Pointing accuracy, without vision of the finger, was recorded each day before treatment. Outcome was measured, by blinded assessors, four days and eight weeks after the end of treatment using the Catherine Bergego Scale (CBS) and the conventional neuropsychological tests from the Behavioural Inattention Test (BIT). Thirty four patients received treatment: 16 with prisms, 18 sham. Mean compliance was 99% and 97%, respectively. Over the treatment days only the prism treated group showed increased leftward bias in open loop pointing to targets on a touch screen. However, despite the group level changes in pointing behaviour no overall effect of the treatment on self-care or BIT were found.

  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. Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials.

    PubMed Central

    Warwick, J.; Kehoe, S.; Earl, H.; Luesley, D.; Redman, C.; Chan, K. K.

    1995-01-01

    The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor. PMID:8519669

  4. Single Institution Feasibility Trials - Cancer Imaging Program

    Cancer.gov

    Within the CIP program, the current R21 mechanism provides potential funding for small, single institution feasibility trials. The current announcement is titled In Vivo Cancer Imaging Exploratory/Developmental Grants.

  5. Single-Cell Analysis in Cancer Genomics.

    PubMed

    Saadatpour, Assieh; Lai, Shujing; Guo, Guoji; Yuan, Guo-Cheng

    2015-10-01

    Genetic changes and environmental differences result in cellular heterogeneity among cancer cells within the same tumor, thereby complicating treatment outcomes. Recent advances in single-cell technologies have opened new avenues to characterize the intra-tumor cellular heterogeneity, identify rare cell types, measure mutation rates, and, ultimately, guide diagnosis and treatment. In this paper we review the recent single-cell technological and computational advances at the genomic, transcriptomic, and proteomic levels, and discuss their applications in cancer research. PMID:26450340

  6. Routine follow up of breast cancer in primary care: randomised trial.

    PubMed Central

    Grunfeld, E.; Mant, D.; Yudkin, P.; Adewuyi-Dalton, R.; Cole, D.; Stewart, J.; Fitzpatrick, R.; Vessey, M.

    1996-01-01

    OBJECTIVE: To assess the effect on time to diagnosis of recurrence and on quality of life of transferring primary responsibility for follow up of women with breast cancer in remission from hospital to general practice. DESIGN: Randomised controlled trial with 18 month follow up in which women received routine follow up either in hospital or in general practice. SUBJECTS AND SETTING: 296 women with breast cancer in remission receiving regular follow up care at district general hospitals in England. MAIN OUTCOME MEASURES: Time between first presentation of symptoms to confirmation of recurrence; quality of life measured by specific dimensions of the SF-36 schedule, the EORTC symptom scale, and hospital anxiety and depression scale. RESULTS: Most recurrences (18/26, 69%) presented as interval events, and almost half (7/16, 44%) of the recurrences in the hospital group presented first to general practice. The median time to hospital confirmation of recurrence was 21 days in the hospital group (range 1-376 days) and 22 days in the general practice group (range 4-64). The differences between groups in the change in SF-36 mean scores from baseline were small: -1.8 (95% confidence interval -7.2 to 3.5) for social functioning, 0.5 (-4.1 to 5.1) for mental health, and 0.6 (-3.6 to 4.8) for general health perception. The change from baseline in the mean depression score was higher in the general practice group at the mid-trial assessment (difference 0.6, 0.1 to 1.2) but there was no significant difference between groups in the anxiety score or the EORTC scales. CONCLUSION: General practice follow up of women with breast cancer in remission is not associated with increase in time to diagnosis, increase in anxiety, or deterioration in health related quality of life. Most recurrences are detected by women as interval events and present to the general practitioner, irrespective of continuing hospital follow up. PMID:8811760

  7. 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

  8. Conquer fear: protocol of a randomised controlled trial of a psychological intervention to reduce fear of cancer recurrence

    PubMed Central

    2013-01-01

    Background Up to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR). Despite the known negative impact of FCR on psychological wellbeing and quality of life, little research has investigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear) based on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer Fear in a randomised controlled trial (RCT). We aim to compare the efficacy and cost-efficacy of the Conquer Fear Intervention and relaxation training in reducing the impact of FCR. Methods/design This study is a multi-centre RCT with 260 participants randomised either to the Conquer Fear Intervention or relaxation training. Both interventions will be delivered in five sessions over 10 weeks by trained psychologists, psychiatrists and social workers with five or more years experience in oncology. Conquer Fear sessions use attentional training, detached mindfulness, meta-cognitive therapy, values clarification and psycho-education to help patients change the way they regulate and respond to thoughts about cancer recurrence. Relaxation training includes training in progressive and passive muscle relaxation, meditative relaxation, visualisation and “quick relaxation” techniques. Relaxation was chosen to control for therapist time and attention and has good face-validity as an intervention. The primary outcome is fear of cancer recurrence. Secondary outcomes include distress, quality of life, unmet needs, and health care utilisation. Participants complete questionnaires prior to starting the intervention, immediately after completing the intervention, 3 and 6 months later. Eligible participants are early-stage breast or colorectal cancer survivors who have completed hospital-based treatment between 2 months and 5 years prior to study entry and report a score in the clinical range on the Fear of Cancer Recurrence Inventory. The

  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. 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

  11. 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

  12. 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

  13. 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

  14. Case management vocational rehabilitation for women with breast cancer after surgery: a feasibility study incorporating a pilot randomised controlled trial

    PubMed Central

    2013-01-01

    Background There is a paucity of methodologically robust vocational rehabilitation (VR) intervention trials. This study assessed the feasibility and acceptability of a VR trial of women with breast cancer to inform the development of a larger interventional study. Methods Women were recruited in Scotland and randomised to either a case management VR service or to usual care. Data were collected on eligibility, recruitment and attrition rates to assess trial feasibility, and interviews conducted to determine trial acceptability. Sick leave days (primary outcome) were self-reported via postal questionnaire every 4 weeks during the first 6 months post-surgery and at 12 months. Secondary outcome measures were change in employment pattern, quality of life and fatigue. Results Of the 1,114 women assessed for eligibility, 163 (15%) were eligible. The main reason for ineligibility was age (>65 years, n = 637, 67%). Of those eligible, 111 (68%) received study information, of which 23 (21%) consented to participate in the study. Data for 18 (78%) women were analysed (intervention: n = 7; control: n = 11). Participants in the intervention group reported, on average, 53 fewer days of sick leave over the first 6 months post-surgery than those in the control group; however, this difference was not statistically significant (p = 0.122; 95% confidence interval −15.8, 122.0). No statistically significant differences were found for secondary outcomes. Interviews with trial participants indicated that trial procedures, including recruitment, randomisation and research instruments, were acceptable. Conclusions Conducting a pragmatic trial of effectiveness of a VR intervention among cancer survivors is both feasible and acceptable, but more research about the exact components of a VR intervention and choice of outcomes to measure effectiveness is required. VR to assist breast cancer patients in the return to work process is an important component of cancer survivorship plans. Trial

  15. 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

  16. 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.

  17. A Prospective Randomised Phase III Clinical Trial Testing the Role of Prophylactic Cranial Radiotherapy in Patients Treated with Trastuzumab for Metastatic Breast Cancer - Anglo Celtic VII.

    PubMed

    Canney, P; Murray, E; Dixon-Hughes, J; Lewsley, L-A; Paul, J

    2015-08-01

    A high incidence of central nervous system (CNS) metastases has been reported in patients with HER2-positive tumours receiving trastuzumab therapy for metastatic breast cancer. This study tested whether prophylactic cranial irradiation (PCI) could reduce the incidence of CNS metastases in this setting. This was a prospective, randomised phase III trial. Patients were randomised 1:1 to no PCI or PCI delivered at around 6 weeks after study entry. Cognitive function was assessed prospectively. In total, 51 patients were randomised over a 3 year period; 25 received PCI and 26 did not. The cumulative incidence of CNS metastases at 2 years was 32.4% (standard error = 9.8%) on the no PCI arm and 21.0% (standard error = 8.6%) on the PCI arm; the associated hazard ratio was 0.57 (95% confidence interval 0.18-1.74; P = 0.32). There was no evidence of cognitive dysfunction in PCI patients.

  18. 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

  19. 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

  20. 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. PMID:27396647

  1. Randomised controlled trial of single, subacromial injection of methylprednisolone in patients with persistent, post-traumatic impingment of the shoulder

    PubMed Central

    McInerney, J; Dias, J; Durham, S; Evans, A

    2003-01-01

    Objective: To evaluate the impact on recovery, of single subacromial injection of methylprednisolone in patients with persistent, post-traumatic impingement of the shoulder. Design: Randomised, controlled study. Setting: Large accident and emergency department in Leicester, UK. Participants: 98 patients with persistent, post-traumatic impingement of the shoulder. Intervention: Single subacromial injection of methylprednisolone with bupivicaine (group S, n=54) or bupivicaine only (group C, n=44). Main outcome measures: Pain using a 10 cm visual analogue scale (VAS) and active shoulder abduction. Results: Comparison of pain scores by the 10 cm VAS between group and group C showed no statistical difference at 3, 6, or 12 weeks. Mean patient pain scores at 12 weeks were 1.38 in both groups (p=0.99). There were 16 patients in group S (mean age 52 years) with a 10 cm VAS greater than 1 (95% CI CI 0.17 to 0.43), compared with 13 patients (mean age 57 years) in group C (95% CI 0.17 to 0.45). Comparison of active shoulder abduction between group S and group C showed no statistical difference at 3, 6, or 12 weeks. Mean active abduction at 12 weeks was 168.9° in group S and 170.3° in group C (p=0.8). There were 10 patients in group S (mean age 60.5) with active abduction less than 170 at 12 weeks (95% CI 0.09 to 0.31), compared with five patients (mean age 62 years) in group C (95% CI 0.04 to 0.24). Conclusions: Single subacromial injection of methylprednisolone has no beneficial impact on reducing the pain, or the duration of immobility in patients with persistent post-traumatic impingement of the shoulder PMID:12748132

  2. Effect of Fee on Cervical Cancer Screening Attendance—ScreenFee, a Swedish Population-Based Randomised Trial

    PubMed Central

    Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

    2016-01-01

    Background Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Method Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Results Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85–1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Conclusion Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. Trial Registration ClinicalTrials.gov NCT02378324 PMID:26986848

  3. 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

  4. 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

  5. A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness

    PubMed Central

    Linsell, L; Forbes, L J L; Kapari, M; Burgess, C; Omar, L; Tucker, L; Ramirez, A J

    2009-01-01

    Background: There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We aimed to test the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. Methods: We randomised 867 women aged 67–70 years attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted 10-min interaction with a radiographer plus a booklet, a booklet alone or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk, and reported breast checking. Results: At 1 month, the intervention increased the proportion who were breast cancer aware compared with usual care (interaction arm: 32.8% vs 4.1%; odds ratio (OR): 24.0, 95% confidence interval (CI): 7.7–73.7; booklet arm: 12.7% vs 4.1%; OR: 4.4, 95% CI: 1.6–12.0). At 1 year, the effects of the interaction plus booklet, and the booklet, on breast cancer awareness were largely sustained, although the interaction plus booklet remained much more effective. Conclusions: An intervention to equip older women with the knowledge, skills, confidence and motivation to detect breast cancer symptoms and seek help promptly increases breast cancer awareness at 1 year. Future research will evaluate whether the intervention promotes early presentation and reduces breast cancer mortality. PMID:19956161

  6. A phase II randomised trial of 5-fluorouracil with or without interferon alpha-2a in advanced colorectal cancer.

    PubMed Central

    Piga, A.; Cascinu, S.; Latini, L.; Marcellini, M.; Bavosi, M.; Acito, L.; Bascioni, R.; Giustini, L.; Francini, G.; Pancotti, A.; Rossi, G.; Del Papa, M.; Carle, F.; Cellerino, R.

    1996-01-01

    With the association of 5-fluorouracil (5-FU) and alpha-interferon (IFN), objective responses as high as 26 63% have been reported in untreated patients with advanced colorectal cancer. However, grade 3-4 toxicity has also been reported. We have conducted a prospective phase II randomised study comparing 5-FU to 5-FU + IFN, to investigate whether the addition of IFN to a weekly 5-FU regimen devoid of significant toxicity used at our institutions could improve the effectiveness of 5-FU while maintaining acceptable toxicity. Patients with histologically proven advanced colorectal carcinoma were randomised to receive 5-FU 500 mg m-2 intravenous (i.v.) bolus on days 1-5 followed by 5-FU 500 mg m-2 i.v. bolus weekly from day 15, with or without IFN alpha-2a intramuscularly (i.m.) 1.5 mU daily on days 6-12 and 3 mU i.m. daily thereafter. The treatment was administered on an outpatient basis. Response was evaluated every 3 months, and treatment continued until progression or after two consecutive judgements of stable disease. Response rate was the main end point of the study. Of 141 patients eligible, 72 were randomised to 5-FU alone (arm A) and 69 to 5-FU + IFN (arm B). Responses were 9/72 (12.5%) in arm A and 6/69 (8.7%) in arm B; complete responses were three in arm A and two in arm B. Progression-free survival (median 4 months) and survival (median 12 months) were identical in the two arms. Toxicity was almost absent in arm A and moderate in arm B, represented mainly by haematological toxicity (usually leucopenia). In conclusion, overall survival was good in both arms of treatment and toxicity was moderate. While the response rate with 5-FU alone was in accord with the literature data, response to 5-FU + IFN was lower than expected. At least at this dosage and schedule, the association of 5-FU and IFN is no better than 5-FU alone and is of no clinical interest. PMID:8826868

  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. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    PubMed

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-01

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions. PMID:24553755

  9. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    PubMed Central

    2009-01-01

    Background Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769 PMID:19807917

  10. Providing general practice needs-based care for carers of people with advanced cancer: a randomised controlled trial

    PubMed Central

    Mitchell, Geoffrey K; Girgis, Afaf; Jiwa, Moyez; Sibbritt, David; Burridge, Letitia H; Senior, Hugh E

    2013-01-01

    Background Carers of patients with advanced cancer often have health and psychosocial needs, which are frequently overlooked. Aim To meet the needs of carers through a GP consultation directed by a self-completed carer needs checklist. Design and setting Randomised controlled trial in general practice with recruitment through specialist oncology clinics, in Brisbane, Australia. Method Intervention was (a) carer–GP consultations directed by a self-completed checklist of needs at baseline and 3 months; and (b) a GP-Toolkit to assist GPs to address carer-identified needs. Control group received usual care. Outcome measures were intensity of needs, anxiety and depression, and quality of life. Results Total recruitment 392. Overall, no significant differences were detected in the number or intensity of need between groups. Compared to controls, intervention participants with baseline clinical anxiety showed improvements in mental wellbeing (P = 0.027), and those with baseline clinical depression had slower development of anxiety (P = 0.044) at 6 months. For those not anxious, physical wellbeing improved at 1 month (P = 0.040). Carers looking after patients with poor functional status had more physical needs (P = 0.037) at 1 month and more psychological and emotional needs at 3 months (P = 0.034). Those caring for less unwell patients showed improved mental wellbeing at 3 months (P = 0.022). Conclusion The intervention did not influence the number or intensity of needs reported by carers of people with advanced cancer. There was limited impact in people with pre-existing clinical anxiety and depression. For the carer of those most severely affected by advanced cancer, it drew attention to the needs arising from the caregiving role. PMID:24152483

  11. 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

  12. Steps toward improving diet and exercise for cancer survivors (STRIDE): a quasi-randomised controlled trial protocol

    PubMed Central

    2014-01-01

    Background Cancer survivorship rates have increased in developed countries largely due to population ageing and improvements in cancer care. Survivorship is a neglected phase of cancer treatment and is often associated with adverse physical and psychological effects. There is a need for broadly accessible, non-pharmacological measures that may prolong disease-free survival, reduce or alleviate co-morbidities and enhance quality of life. The aim of the Steps TowaRd Improving Diet and Exercise (STRIDE) study is to evaluate the effectiveness of an online-delivered physical activity intervention for increasing walking in cancer survivors living in metropolitan and rural areas of South Australia. Methods/Design This is a quasi-randomised controlled trial. The intervention period is 12-weeks with 3-month follow-up. The trial will be conducted at a university setting and community health services in South Australia. Participants will be insufficiently active and aged 18 years or older. Participants will be randomly assigned to either the intervention or control group. All participants will receive a pedometer but only the intervention group will have access to the STRIDE website where they will report steps, affect and ratings of perceived exertion (RPE) during exercise daily. Researchers will use these variables to individualise weekly step goals to increase walking. The primary outcome measure is steps per day. The secondary outcomes are a) health measures (anthropometric and physiological), b) dietary habits (consumption of core foods and non-core foods) and c) quality of life (QOL) including physical, psychological and social wellbeing. Measures will be collected at baseline, post-intervention and 3-month follow-up. Discussion This protocol describes the implementation of a trial using an online resource to assist cancer survivors to become more physically active. It is an innovative tool that uses ratings of perceived exertion and daily affect to create

  13. Lack of Effect of Lowering LDL Cholesterol on Cancer: Meta-Analysis of Individual Data from 175,000 People in 27 Randomised Trials of Statin Therapy

    PubMed Central

    2012-01-01

    Background Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py

  14. 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

  15. A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC)

    PubMed Central

    Senkus-Konefka, E; Dziadziuszko, R; Bednaruk-Młyński, E; Pliszka, A; Kubrak, J; Lewandowska, A; Małachowski, K; Wierzchowski, M; Matecka-Nowak, M; Jassem, J

    2005-01-01

    A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47–81 years (mean 66), performance status 1–4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC. PMID:15770205

  16. Clinician-led improvement in cancer care (CLICC) - testing a multifaceted implementation strategy to increase evidence-based prostate cancer care: phased randomised controlled trial - study protocol

    PubMed Central

    2014-01-01

    Background Clinical practice guidelines have been widely developed and disseminated with the aim of improving healthcare processes and patient outcomes but the uptake of evidence-based practice remains haphazard. There is a need to develop effective implementation methods to achieve large-scale adoption of proven innovations and recommended care. Clinical networks are increasingly being viewed as a vehicle through which evidence-based care can be embedded into healthcare systems using a collegial approach to agree on and implement a range of strategies within hospitals. In Australia, the provision of evidence-based care for men with prostate cancer has been identified as a high priority. Clinical audits have shown that fewer than 10% of patients in New South Wales (NSW) Australia at high risk of recurrence after radical prostatectomy receive guideline recommended radiation treatment following surgery. This trial will test a clinical network-based intervention to improve uptake of guideline recommended care for men with high-risk prostate cancer. Methods/Design In Phase I, a phased randomised cluster trial will test a multifaceted intervention that harnesses the NSW Agency for Clinical Innovation (ACI) Urology Clinical Network to increase evidence-based care for men with high-risk prostate cancer following surgery. The intervention will be introduced in nine NSW hospitals over 10 months using a stepped wedge design. Outcome data (referral to radiation oncology for discussion of adjuvant radiotherapy in line with guideline recommended care or referral to a clinical trial of adjuvant versus salvage radiotherapy) will be collected through review of patient medical records. In Phase II, mixed methods will be used to identify mechanisms of provider and organisational change. Clinicians’ knowledge and attitudes will be assessed through surveys. Process outcome measures will be assessed through document review. Semi-structured interviews will be conducted to elucidate

  17. On the use of prostate-specific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer.

    PubMed

    Bangma, Chris H; van Schaik, Ron H; Blijenberg, Bert G; Roobol, Monique J; Lilja, Hans; Stenman, Ulf-Håkan

    2010-11-01

    Prostate-specific antigen (PSA) has been the main drive for early detection of prostate cancer (PCa), including in population-based screening as in the European Randomised Study for Screening of Prostate Cancer (ERSPC). The specificity of PSA to indicate men with biopsy detectable prostate cancer can be improved by adding information obtained by new biomarkers, such as PSA isoforms. This improvement is needed to increase the efficacy of the screening procedure for the population-based as well as the individual screening. Various PSA isoforms, kallikreins and molecular markers have been validated in various cohorts from ERSPC of men with and without PCa in order to design the optimal diagnostic procedure for screening asymptomatic men. So far, most promising results have been obtained from the analysis of free PSA, proPSA, nicked PSA and hK2. The use of free PSA in addition to total PSA reduces the number of negative sextant biopsies at a PSA cut-off level of 3 ng/ml at initial screening with 30%, at the cost of losing 10% of detectable cancers that are predominantly well differentiated on histology. Further addition of PSA isoforms and hK2 only improve ROC curves in selected samples by a maximum of 5%. Molecular markers like PCA3 and TMPRSS2 in urine do not appear to be useful but they have been assessed insufficiently so far. The level of PSA at initial screening is highly predictive for the chance of being diagnosed with PCa later on in life. The changes in PSA over time after initial screening (like PSA-velocity and PSA-doubling time) are statistically different between men with detectable cancers versus those without (PSA-doubling time 5.1 versus 6.1 years), but this does not contribute significantly to population-based screening overall. Changes in specificity need to be related to a cost efficacy evaluation in the final analysis of ERSPC. PMID:21047594

  18. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer

    PubMed Central

    Kümmel, S; Krocker, J; Kohls, A; Breitbach, G-P; Morack, G; Budner, M; Blohmer, J-U; Elling, D

    2006-01-01

    We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles, then cyclophosphamide 600 mg m−2, methotrexate 40 mg m−2, and fluorouracil 600 mg m−2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 μg kg day−1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer. PMID:16622463

  19. 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

  20. Randomised trial of expressive writing for distressed metastatic breast cancer patients.

    PubMed

    Mosher, Catherine E; Duhamel, Katherine N; Lam, Joanne; Dickler, Maura; Li, Yuelin; Massie, Mary Jane; Norton, Larry

    2012-01-01

    Women with metastatic breast cancer and significant psychological distress (N = 87) were assigned randomly to engage in four home-based sessions of expressive writing or neutral writing. Women in the expressive writing group wrote about their deepest thoughts and feelings regarding their cancer, whereas women in the neutral writing group wrote about their daily activities in a factual manner. No statistically significant group differences in existential and psychological well-being, fatigue and sleep quality were found at 8-weeks post-writing. However, the expressive writing group reported significantly greater use of mental health services during the study than the neutral writing group (55% vs. 26%, respectively; p < 0.05). Findings suggest that expressive writing may improve the uptake of mental health services among distressed cancer patients, but is not broadly effective as a psychotherapeutic intervention.

  1. Evaluation of a complex intervention to improve activities of daily living of disabled cancer patients: protocol for a randomised controlled study and feasibility of recruitment and intervention

    PubMed Central

    2014-01-01

    Background Many cancer patients have problems performing activities of daily living (ADL). A randomised controlled trial was designed to examine the effects of an ADL intervention in addition to standard treatment and care in a hospital setting. The objective of this article was to present the study and to analyse the feasibility of the recruitment process and the intervention. Methods Adult disabled cancer patients at Næstved Hospital in Denmark were enrolled between 1 March 2010 and 30 June 2011 and randomised into an ADL intervention or to a control group. The intervention was performed by occupational therapists. The feasibility of the recruitment was analysed with regard to success in achieving the estimated number of participants and identification of barriers, and feasibility of the intervention was based on calculations of patient attendance and patient acceptability. The primary outcome of the randomised controlled trial was patients’ health-related quality of life 2 and 8 weeks after baseline. Results A total of 118 disabled cancer patients were enrolled in the study over a time span of 16 months. Very few meetings between occupational therapist and patient were cancelled. Time spent on the intervention varied considerably, but for the majority of patients, time consumption was between 1–3 hours. Conclusions Despite difficulties with recruitment, participation was considered feasible and the intervention was accepted among patients. Missing data in the follow-up period were mostly due to death among participants. Very few participants declined to complete questionnaires during follow-up. PMID:24779438

  2. A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

    PubMed Central

    James, L. E.; Gower, N. H.; Rudd, R. M.; Spiro, S. G.; Harper, P. G.; Trask, C. W.; Partridge, M.; Ruiz de Elvira, M. C.; Souhami, R. L.

    1996-01-01

    We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to

  3. Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials.

    PubMed

    Teleni, Laisa; Chan, Raymond J; Chan, Alexandre; Isenring, Elisabeth A; Vela, Ian; Inder, Warrick J; McCarthy, Alexandra L

    2016-02-01

    Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort.

  4. Randomised, single-masked non-inferiority trial of femtosecond laser-assisted versus manual phacoemulsification cataract surgery for adults with visually significant cataract: the FACT trial protocol

    PubMed Central

    Day, Alexander C; Burr, Jennifer M; Bunce, Catey; Doré, Caroline J; Sylvestre, Yvonne; Wormald, Richard P L; Round, Jeff; McCudden, Victoria; Rubin, Gary; Wilkins, Mark R

    2015-01-01

    Introduction Cataract is one of the leading causes of low vision in the westernised world, and cataract surgery is one of the most commonly performed operations. Laser platforms for cataract surgery are now available, the anticipated advantages of which are broad and may include better visual outcomes through greater precision and reproducibility, and improved safety. FACT is a randomised single masked non-inferiority trial to establish whether laser-assisted cataract surgery is as good as or better than standard manual phacoemulsification. Methods and analysis 808 patients aged 18 years and over with visually significant cataract will be randomised to manual phacoemulsification cataract surgery (standard care) or laser-assisted cataract surgery (intervention arm). Outcomes will be measured at 3 and 12 months after surgery. The primary clinical outcome is uncorrected distance visual acuity (UDVA, logMAR) at 3 months in the study eye recorded by an observer masked to the trial group. Secondary outcomes include UDVA at 12 months, corrected distance visual acuity at 3 and 12 months, complications, endothelial cell loss, patient-reported outcome measures and a health economic analysis conforming to National Institute for Health and Care Excellence standards. Ethics and dissemination Research Ethics Committee Approval was obtained on 6 February 2015, ref: 14/LO/1937. Current protocol: v2.0 (08/04/2015). Study findings will be published in peer-reviewed journals. Trial registration number ISRCTN: 77602616. PMID:26614627

  5. 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.

  6. 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. PMID:25153949

  7. Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer

    PubMed Central

    Emery, Jon; Doorey, Juanita; Jefford, Michael; King, Madeleine; Pirotta, Marie; Hayne, Dickon; Martin, Andrew; Trevena, Lyndal; Lim, Tee; Constable, Roger; Hawks, Cynthia; Hyatt, Amelia; Hamid, Akhlil; Violet, John; Gill, Suki; Frydenberg, Mark; Schofield, Penelope

    2014-01-01

    Introduction Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. Methods and analysis The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. Results of this phase II trial will be reported in peer-reviewed publications and in conference presentations. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12610000938000 PMID:24604487

  8. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    Summary Background The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). Methods In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per

  9. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

    PubMed

    Bramhall, S R; Schulz, J; Nemunaitis, J; Brown, P D; Baillet, M; Buckels, J A C

    2002-07-15

    Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified. PMID

  10. The effect of information about overdetection of breast cancer on women's decision-making about mammography screening: study protocol for a randomised controlled trial

    PubMed Central

    Hersch, Jolyn; Barratt, Alexandra; Jansen, Jesse; Houssami, Nehmat; Irwig, Les; Jacklyn, Gemma; Dhillon, Haryana; Thornton, Hazel; McGeechan, Kevin; Howard, Kirsten; McCaffery, Kirsten

    2014-01-01

    Introduction Women are largely unaware that mammography screening can cause overdetection of inconsequential disease, leading to overdiagnosis and overtreatment of breast cancer. Evidence is lacking about how information on overdetection affects women's breast screening decisions and experiences. This study investigates the consequences of providing information about overdetection of breast cancer to women approaching the age of invitation to mammography screening. Methods and analysis This is a randomised controlled trial with an embedded longitudinal qualitative substudy. Participants are a community sample of women aged 48–50 in New South Wales, Australia, recruited in 2014. Women are randomly allocated to either quantitative only follow-up (n=904) or additional qualitative follow-up (n=66). Women in each stream are then randomised to receive either the intervention (evidence-based information booklet including overdetection, breast cancer mortality reduction and false positives) or a control information booklet (including mortality reduction and false positives only). The primary outcome is informed choice about breast screening (adequate knowledge, and consistency between attitudes and intentions) assessed via telephone interview at 2 weeks postintervention. Secondary outcomes measured at this time include decision process (decisional conflict and confidence) and psychosocial outcomes (anticipated regret, anxiety, breast cancer worry and perceived risk). Women are further followed up at 6 months, 1 and 2 years to assess self-reported screening behaviour and long-term psychosocial outcomes (decision regret, quality of life). Participants in the qualitative stream undergo additional in-depth interviews at each time point to explore the views and experiences of women who do and do not choose to have screening. Ethics and dissemination The study has ethical approval, and results will be published in peer-reviewed journals. This research will help ensure

  11. A prospective randomised study of anatomical single-bundle versus double-bundle anterior cruciate ligament reconstruction: quantitative evaluation using an electromagnetic measurement system.

    PubMed

    Araki, Daisuke; Kuroda, Ryosuke; Kubo, Seiji; Fujita, Norifumi; Tei, Katsumasa; Nishimoto, Koji; Hoshino, Yuichi; Matsushita, Takehiko; Matsumoto, Tomoyuki; Nagamune, Koki; Kurosaka, Masahiro

    2011-03-01

    We conducted a prospective randomised study of anatomical single-bundle (A-SB group) versus double-bundle (A-DB group) anterior cruciate ligament (ACL) reconstruction using the hamstrings tendons. Twenty patients with unilateral ACL deficiency were randomised into two groups. We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group. All of the patients were tested before ACL reconstruction and one year after surgery. The KT-1000 measurements, isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score. For pre- and postoperative stability assessment, we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device (the EMS) for quantitative assessment during the Lachman test and the pivot shift test. There were no significant differences in the KT-1000 measurements, isokinetic muscle peak torque, heel-height difference, and Lysholm score at one-year follow-up between these two groups. The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group. In conclusion, clinical outcomes were equally good in both groups. However, the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction.

  12. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial

    PubMed Central

    Cuzick, Jack; Pierotti, Paola; Cariaggi, Maria Paola; Palma, Paolo Dalla; Naldoni, Carlo; Ghiringhello, Bruno; Giorgi-Rossi, Paolo; Minucci, Daria; Parisio, Franca; Pojer, Ada; Schiboni, Maria Luisa; Sintoni, Catia; Zorzi, Manuel; Segnan, Nereo; Confortini, Massimo

    2007-01-01

    Objective To compare the accuracy of conventional cytology with liquid based cytology for primary screening of cervical cancer. Design Randomised controlled trial. Setting Nine screening programmes in Italy. Participants Women aged 25-60 attending for a new screening round: 22 466 were assigned to the conventional arm and 22 708 were assigned to the experimental arm. Interventions Conventional cytology compared with liquid based cytology and testing for human papillomavirus. Main outcome measure Relative sensitivity for cervical intraepithelial neoplasia of grade 2 or more at blindly reviewed histology, with atypical cells of undetermined significance or more severe cytology considered a positive result. Results In an intention to screen analysis liquid based cytology showed no significant increase in sensitivity for cervical intraepithelial neoplasia of grade 2 or more (relative sensitivity 1.17, 95% confidence interval 0.87 to 1.56) whereas the positive predictive value was reduced (relative positive predictive value v conventional cytology 0.58, 0.44 to 0.77). Liquid based cytology detected more lesions of grade 1 or more (relative sensitivity 1.68, 1.40 to 2.02), with a larger increase among women aged 25-34 (P for heterogeneity 0.0006), but did not detect more lesions of grade 3 or more (relative sensitivity 0.84, 0.56 to 1.25). Results were similar when only low grade intraepithelial lesions or more severe cytology were considered a positive result. No evidence was found of heterogeneity between centres or of improvement with increasing time from start of the study. The relative frequency of women with at least one unsatisfactory result was lower with liquid based cytology (0.62, 0.56 to 0.69). Conclusion Liquid based cytology showed no statistically significant difference in sensitivity to conventional cytology for detection of cervical intraepithelial neoplasia of grade 2 or more. More positive results were found, however, leading to a lower positive

  13. Cancer: a single disease with a multitude of manifestions?

    PubMed Central

    Grandics, Peter

    2003-01-01

    The relationships of critical nutrients such as plant phenolics, vitamins, minerals and lipids are considered with respect to the incidence of a variety of cancers, and analyzed in terms of how these nutrient deficiencies alter immune function, DNA integrity and cell proliferation. With a significant correlation found between cancer and these nutrient deficiencies, the hypothesis is presented here that nutrition could provide a unifying perception of cancer and recast it as a single disease. This further suggests that a coordinated administration of specific, critical nutrients to cancer patients could lead to the reversal of the disease. It is also proposed that the concurrent presence of a variety of nutritional deficiencies in cancer patients requires a multilevel, systemic approach to this disease as opposed to the single active therapeutic agent approach that is the cornerstone of contemporary research and pharmacology. PMID:14624698

  14. Male breast cancer - a single center experience

    PubMed Central

    Bystricky, Branislav; Kohutek, Filip; Rosik, Andrej

    2016-01-01

    Due to its rarity, male breast cancer remains a poorly characterized disease. The present study obtained retrospective clinicopathological data, treatment patterns and outcomes for all male patients diagnosed with breast cancer in the Oncology Department, Faculty Hospital Trenčín (Trenčín, Slovakia) over the last 20 years from January 1995 to December 2015. A total of 21 patients with male breast cancer were analyzed, with a median patient age of 65.6 years. Two patients were diagnosed with lobular invasive cancer; all others were diagnosed with cancer of a ductal origin. One patient presented with metastatic disease in the pleural cavity. The primary tumors in 8 patients were staged as pT1, whilst 6 patients were staged as pT2 and 7 as pT4. Axillary lymph node involvement was present in 11 patients (52%) and 15 patients were hormone receptor-positive (83%). All but 1 patient underwent mastectomy and surgical staging of the axilla. Adjuvant chemotherapy, radiotherapy and hormone treatment was administered in the same manner as breast cancer treatment in female patients. The median follow-up time was 4.5 years. The 5- and 10-year overall survival rates were 87 and 74%, respectively, and the estimated median disease-free survival for the same population was 9.5 years (95% confidence interval, 6.2–14.6). The survival rates reported in the present retrospective study are comparable with previously published studies. In addition, the current study reported predominant hormone-positive characteristics and rare expression of human epidermal growth factor receptor 2. However, further multi-institutional trials are required to allow for informed treatment decisions in this uncommon disease. PMID:27446481

  15. A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

    PubMed Central

    Fruscio, R; Colombo, N; Lissoni, A A; Garbi, A; Fossati, R; Ieda', N; Torri, V; Mangioni, C

    2008-01-01

    To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77–93%) in the CIP arm and 90% (95% CI 84–96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach. PMID:18253120

  16. 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

  17. 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

  18. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study

    PubMed Central

    Fizazi, Karim; Carducci, Michael; Smith, Matthew; Damião, Ronaldo; Brown, Janet; Karsh, Lawrence; Milecki, Piotr; Shore, Neal; Rader, Michael; Wang, Huei; Jiang, Qi; Tadros, Sylvia; Dansey, Roger; Goessl, Carsten

    2011-01-01

    Summary Background Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. Methods In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. Findings 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab compared with 17·1

  19. Milk supplementation facilitates appetite control in obese women during weight loss: a randomised, single-blind, placebo-controlled trial.

    PubMed

    Gilbert, Jo-Anne; Joanisse, Denis R; Chaput, Jean-Philippe; Miegueu, Pierre; Cianflone, Katherine; Alméras, Natalie; Tremblay, Angelo

    2011-01-01

    Dairy products provide Ca and protein which may facilitate appetite control. Conversely, weight loss is known to increase the motivation to eat. This randomised controlled trial verified the influence of milk supplementation on appetite markers during weight loss. Low Ca consumer women participated in a 6-month energy-restricted programme (-2508 kJ/d or -600 kcal/d) and received either a milk supplementation (1000 mg Ca/d) or an isoenergetic placebo (n 13 and 12, respectively). Fasting appetite sensations were assessed by visual analogue scales. Anthropometric parameters and fasting plasma concentrations of glucose, insulin, leptin, ghrelin and cortisol were measured as well. Both groups showed a significant weight loss (P < 0·0001). In the milk-supplemented group, a time x treatment interaction effect showed that weight loss with milk supplementation induced a smaller increase in desire to eat and hunger (P < 0·05). Unlike the placebo group, the milk-supplemented group showed a lower than predicted decrease in fullness (-17·1 v. -8·8; -2·7 v. 3·3 mm, P < 0·05, measured v. predicted values, respectively). Even after adjustment for fat mass loss, changes in ghrelin concentration predicted those in desire to eat (r 0·56, P < 0·01), hunger (r 0·45, P < 0·05) and fullness (r -0·40, P < 0·05). However, the study did not show a between-group difference in the change in ghrelin concentration in response to the intervention. These results show that milk supplementation attenuates the orexigenic effect of body weight loss. PMID:21205360

  20. 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. PMID:27418551

  1. Primary care endorsement letter and a patient leaflet to improve participation in colorectal cancer screening: results of a factorial randomised trial

    PubMed Central

    Hewitson, P; Ward, A M; Heneghan, C; Halloran, S P; Mant, D

    2011-01-01

    Background: The trial aimed to investigate whether a general practitioner's (GP) letter encouraging participation and a more explicit leaflet explaining how to complete faecal occult blood test (FOBT) included with the England Bowel Cancer Screening Programme invitation materials would improve uptake. Methods: A randomised controlled 2 × 2 factorial trial was conducted in the south of England. Overall, 1288 patients registered with 20 GPs invited for screening in October 2009 participated in the trial. Participants were randomised to either a GP's endorsement letter and/or an enhanced information leaflet with their FOBT kit. The primary outcome was verified with return of the test kit within 20 weeks. Results: Both the GP's endorsement letter and the enhanced procedural leaflet, each increased participation by ∼6% – the GP's letter by 5.8% (95% CI: 4.1–7.8%) and the leaflet by 6.0% (95% CI: 4.3–8.1%). On the basis of the intention-to-treat analysis, the random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP's letter and 1.12 (P=0.029) for the leaflet. In the absence of an interaction, an additive effect for receiving both the GP's letter and leaflet (11.8%, 95% CI: 8.5–16%) was confirmed. The per-protocol analysis indicated that the insertion of an electronic GP's signature on the endorsement letter was associated with increased participation (P=0.039). Conclusion: Including both an endorsement letter from each patient's GP and a more explicit procedural leaflet could increase participation in the English Bowel Cancer Screening Programme by ∼10%, a relative improvement of 20% on current performance. PMID:21829202

  2. 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

  3. Randomised, placebo-controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer.

    PubMed

    Harrington, C; Campbell, G; Wynne, C; Atkinson, C

    2010-06-01

    Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer. PMID:20598010

  4. 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

  5. Direct improvement of quality of life using a tailored quality of life diagnosis and therapy pathway: randomised trial in 200 women with breast cancer

    PubMed Central

    Klinkhammer-Schalke, M; Koller, M; Steinger, B; Ehret, C; Ernst, B; Wyatt, J C; Hofstädter, F; Lorenz, W

    2012-01-01

    Background: Despite thousands of papers, the value of quality of life (QoL) in curing disease remains uncertain. Until now, we lacked tools for the diagnosis and specific treatment of diseased QoL. We approached this problem stepwise by theory building, modelling, an exploratory trial and now a definitive randomised controlled trial (RCT) in breast cancer, whose results we report here. Methods: In all, 200 representative Bavarian primary breast cancer patients were recruited by five hospitals and treated by 146 care professionals. Patients were randomised to either (1) a novel care pathway including diagnosis of ‘diseased' QoL (any QoL measure below 50 points) using a QoL profile and expert report sent to the patient's coordinating practitioner, who arranged QoL therapy consisting of up to five standardised treatments for specific QoL defects or (2) standard postoperative care adhering to the German national guideline for breast cancer. The primary end point was the proportion of patients in each group with diseased QoL 6 months after surgery. Patients were blinded to their allocated group. Results: At 0 and 3 months after surgery, diseased QoL was diagnosed in 70% of patients. The QoL pathway reduced rates of diseased QoL to 56% at 6 months, especially in emotion and coping, compared with 71% in controls (P=0.048). Relative risk reduction was 21% (95% confidence interval (CI): 0–37), absolute risk reduction 15% (95% CI: 0.3–29), number needed to treat (NNT)=7 (95% CI: 3–37). When QoL therapy finished after successful treatment, diseased QoL often returned again, indicating good responsiveness of the QoL pathway. Conclusion: A three-component outcome system including clinician-derived objective, patient-reported subjective end points and qualitative analysis of clinical relevance was developed in the last 10 years for cancer as a complex intervention. A separate QoL pathway was implemented for the diagnosis and treatment of diseased QoL and its

  6. 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

  7. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial

    PubMed Central

    2008-01-01

    Summary Background The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2·0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2·0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. Methods Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy over 5 weeks or 40 Gy in 15 fractions of 2·67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. Findings 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6·0 years (IQR 5·0–6·2) the rate of local-regional tumour relapse at 5 years was 2·2% (95% CI 1·3–3·1) in the 40 Gy group and 3·3% (95% CI 2·2 to 4·5) in the 50 Gy group, representing an absolute difference of −0·7% (95% CI −1·7% to 0·9%)—ie, the absolute difference in local-regional relapse could be up to 1·7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. Interpretation A radiation schedule

  8. 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

  9. Genetic test to stop smoking (GeTSS) trial protocol: randomised controlled trial of a genetic test (Respiragene) and Auckland formula to assess lung cancer risk

    PubMed Central

    2014-01-01

    Background A gene-based estimate of lung cancer risk in smokers has been shown to act as a smoking cessation motivator in hospital recruited subjects. The objective of this trial is to determine if this motivator is as effective in subjects recruited from an NHS primary care unit. Method/Design Subjects will be recruited by mailings using smoking entries on the GP electronic data-base (total practice population = 32,048) to identify smokers who may want to quit. Smoking cessation clinics based on medical centre premises will run for eight weeks. Clinics will be randomised to have the gene-based test for estimation of lung cancer risk or to act as controls groups. The primary endpoint will be smoking cessation at eight weeks and six months. Secondary outcomes will include ranking of the gene-based test with other smoking cessation motivators. Discussion The results will inform as to whether the gene-based test is both effective as motivator and acceptable to subjects recruited from primary care. Trial registration Registered with Clinical Trials.gov, Registration number: NCT01176383. PMID:24884942

  10. 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

  11. 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

  12. A randomised, single-blind technical study comparing the ultrasonic visibility of smooth-surfaced and textured needles in a soft embalmed cadaver model.

    PubMed

    Munirama, S; Joy, J; Columb, M; Habershaw, R; Eisma, R; Corner, G; Cochran, S; McLeod, G

    2015-05-01

    Visibility of the needle tip and shaft is important during ultrasound-guided regional anaesthesia in order to prevent nerve trauma. Tip and shaft visibility is reduced when needles are inserted in-plane at wide angles and out-of-plane at narrow angles to the ultrasound probe. Although textured needles are more reflective than smooth needles, we hypothesised that poor visibility of the tip and shaft still remained using the above angle-probe combinations. In a single-blind study, we compared the visibility of a textured Tuohy needle, a textured single-shot needle and a conventional smooth-surfaced Tuohy needle when inserted into the biceps and deltoid muscles of a soft embalmed cadaver. One hundred and forty-four needles were block-randomised to in-plane and out-of-plane insertions at 30°, 45°, 60° and 75° to the ultrasound beam. Two blinded raters assessed needle tip visibility on video recordings of the insertions using a binary scale (0 = not visible, 1 = visible) and shaft visibility using a 5-point Likert scale. The median (IQR [range]) proportions of visible needle tips were 83% (67-83 [50-100]%) for the textured Tuohy, 75% (67-83 [33-83]%) for the textured single-shot needle and 33% (33-46 [0-50]%) for the smooth-surfaced Tuohy (p = 0.0007). Median (IQR [range]) needle shaft visibility was rated as 4.0 (3.5-4.7 [3.0-4.9]) for the textured Tuohy, 4.0 (3.8-4.5 [2.7-4.9]) for the textured single-shot needle and 3.0 (2.4-3.3 [2.3-3.5]) for the smooth-surfaced Tuohy (p = 0.015). Nevertheless, visibility was reduced at wide angles in-plane and narrow angles out-of-plane both for needle tips (p = 0.004) and shafts (p = 0.005).

  13. High-Dimensional Single-Cell Cancer Biology

    PubMed Central

    Doxie, Deon B.

    2014-01-01

    Cancer cells are distinguished from each other and from healthy cells by features that drive clonal evolution and therapy resistance. New advances in high-dimensional flow cytometry make it possible to systematically measure mechanisms of tumor initiation, progression, and therapy resistance on millions of cells from human tumors. Here we describe flow cytometry techniques that enable a ‘single-cell systems biology’ view of cancer. High-dimensional techniques like mass cytometry enable multiplexed single-cell analysis of cell identity, clinical biomarkers, signaling network phospho-proteins, transcription factors, and functional readouts of proliferation, cell cycle status, and apoptosis. This capability pairs well with a signaling profiles approach that dissects mechanism by systematically perturbing and measuring many nodes in a signaling network. Single-cell approaches enable study of cellular heterogeneity of primary tissues and turn cell subsets into experimental controls or opportunities for new discovery. Rare populations of stem cells or therapy resistant cancer cells can be identified and compared to other types of cells within the same sample. In the long term, these techniques will enable tracking of minimal residual disease (MRD) and disease progression. By better understanding biological systems that control development and cell-cell interactions in healthy and diseased contexts, we can learn to program cells to become therapeutic agents or target malignant signaling events to specifically kill cancer cells. Single-cell approaches that provide deep insight into cell signaling and fate decisions will be critical to optimizing the next generation of cancer treatments combining targeted approaches and immunotherapy. PMID:24671264

  14. 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

  15. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer

    PubMed Central

    Dalgleish, Angus G; Stebbing, Justin; Adamson, Douglas JA; Arif, Seema Safia; Bidoli, Paolo; Chang, David; Cheeseman, Sue; Diaz-Beveridge, Robert; Fernandez-Martos, Carlos; Glynne-Jones, Rob; Granetto, Cristina; Massuti, Bartomeu; McAdam, Karen; McDermott, Raymond; Martín, Andrés J Muñoz; Papamichael, Demetris; Pazo-Cid, Roberto; Vieitez, Jose M; Zaniboni, Alberto; Carroll, Kevin J; Wagle, Shama; Gaya, Andrew; Mudan, Satvinder S

    2016-01-01

    Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study. PMID:27599039

  16. A single-blind randomised controlled trial of the effects of a web-based decision aid on self-testing for cholesterol and diabetes. study protocol

    PubMed Central

    2012-01-01

    Background Self-tests, tests on body materials to detect medical conditions, are widely available to the general public. Self-testing does have advantages as well as disadvantages, and the debate on whether self-testing should be encouraged or rather discouraged is still ongoing. One of the concerns is whether consumers have sufficient knowledge to perform the test and interpret the results. An online decision aid (DA) with information on self-testing in general, and test specific information on cholesterol and diabetes self-testing was developed. The DA aims to provide objective information on these self-tests as well as a decision support tool to weigh the pros and cons of self-testing. The aim of this study is to evaluate the effect of the online decision aid on knowledge on self-testing, informed choice, ambivalence and psychosocial determinants. Methods/Design A single blind randomised controlled trial in which the online decision aid 'zelftestwijzer' is compared to short, non-interactive information on self-testing in general. The entire trial will be conducted online. Participants will be selected from an existing Internet panel. Consumers who are considering doing a cholesterol or diabetes self-test in the future will be included. Outcome measures will be assessed directly after participants have viewed either the DA or the control condition. Weblog files will be used to record participants' use of the decision aid. Discussion Self-testing does have important pros and cons, and it is important that consumers base their decision whether they want to do a self-test or not on knowledge and personal values. This study is the first to evaluate the effect of an online decision aid for self-testing. Trial registration Dutch Trial Register: NTR3149 PMID:22216905

  17. Low-intensity case management increases contact with primary care in recently released prisoners: a single-blinded, multisite, randomised controlled trial

    PubMed Central

    Alati, Rosa; Longo, Marie; Spittal, Matthew J; Boyle, Frances M; Williams, Gail M; Lennox, Nicholas G

    2016-01-01

    Background The world prison population is large and growing. Poor health outcomes after release from prison are common, but few programmes to improve health outcomes for ex-prisoners have been rigorously evaluated. The aim of this study was to evaluate the impact of individualised case management on contact with health services during the first 6 months post-release. Methods Single-blinded, randomised, controlled trial. Baseline assessment with N=1325 adult prisoners in Queensland, Australia, within 6 weeks of expected release; follow-up interviews 1, 3 and 6 months post-release. The intervention consisted of provision of a personalised booklet (‘Passport’) at the time of release, plus up to four brief telephone contacts in the first 4 weeks post-release. Results Of 1179 eligible participants, 1003 (85%) completed ≥1 follow-up interview. In intention-to-treat analyses, 53% of the intervention group and 41% of the control group reported contacting a general practitioner (GP) at 1 month post-release (difference=12%, 95% CI 5% to 19%). Similar effects were observed for GP contact at 3 months (difference=9%, 95% CI 2% to 16%) and 6 months (difference=8%, 95% CI 1% to 15%), and for mental health (MH) service contact at 6 months post release (difference=8%, 95% CI 3% to 14%). Conclusions Individualised case management in the month after release from prison increases usage of primary care and MH services in adult ex-prisoners for at least 6 months post-release. Given the poor health profile of ex-prisoners, there remains an urgent need to develop and rigorously evaluate interventions to increase health service contact in this profoundly marginalised population. Trial registration number ACTRN12608000232336. PMID:26787201

  18. Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

    PubMed Central

    2010-01-01

    Background It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. Methods/Design The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. Discussion This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion

  19. Final results and pharmacoeconomic analysis of a trial comparing two neoadjuvant chemotherapy (CT) regimens followed by surgery in patients with resectable non-small cell lung cancer (NSCLC): a phase II randomised study by the European Lung Cancer Working Party.

    PubMed

    Berghmans, T; Lafitte, J J; Giner, V; Berchier, M C; Scherpereel, A; Lewin, D; Paesmans, M; Meert, A P; Bosschaerts, T; Leclercq, N; Sculier, J P

    2012-09-01

    Induction cisplatin-based CT improves survival in resectable non-small cell lung cancer (NSCLC). We aimed to determine the respective activity of third-generation (gemcitabine-vinorelbine-cisplatin [GVP]) in comparison with second-generation drugs CT (mitomycine-ifosfamide-cisplatin [MIP]) and their cost-effectiveness as neoadjuvant CT before surgery in NSCLC. Patients with histologically proven initially untreated resectable stages I-III NSCLC were randomised between three courses of MIP or GVP followed by surgery. A two-stage Simon design was used for each arm with resectability rate as primary endpoint. A cost minimisation analysis, considering the direct medical costs, was performed in the Belgian and French social security systems. From 2001 to 2007, 140 patients (pts) were randomised (MIP 69, GVP 71). Main characteristics were: stage I/II/III in 52, 37 and 51 pts, squamous histology in 82 pts, male 114 pts, median PS 90. Objective response rates to induction CT were 60% (MIP) and 65% (GVP) (p=0.55). Complete resection rates were 77% (MIP) and 80% (GVP) (p=0.62). Median survival times were 47.2 months (MIP) and 36.6 months (GVP) (p=0.41). Cost-analyses showed significant incremental costs with GVP. In conclusion, while both neoadjuvant chemotherapy regimens shared similar efficacy in patients with resectable NSCLC, costs were significantly higher for third-generation regimens.

  20. Neoadjuvant Bevacizumab plus Chemotherapy versus Chemotherapy Alone to Treat Non-Metastatic Breast Cancer: A Meta-Analysis of Randomised Controlled Trials

    PubMed Central

    Liu, Min-feng; Chen, Lu-jia; Hu, Xiao-lei; Ye, Chang-sheng

    2015-01-01

    Purpose Results from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting. Methods A literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3. Results Nine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18–1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17–1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90–3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09–1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78–2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand–foot syndrome. Conclusions Higher proportions of patients achieved pCR when

  1. Relating Single Cell Heterogeneity To Genotype During Cancer Progression

    NASA Astrophysics Data System (ADS)

    Rajaram, Satwik

    2013-03-01

    Progression of normal cells towards cancer is driven by a series of genetic changes. Traditional population-averaged measurements have found that cell signalling activities are increasingly altered during this progression. Despite the fact that cancer cells are known to be highly heterogeneous, the response of individual pathways to specific genetic changes remains poorly characterized at a single cell level. Do signalling alterations in a pathway reflect a shift of the whole population, or changes to specific subpopulations? Are alterations to pathways independent, or are cells with alterations in one pathway more likely to be abnormal in another due to crosstalk? We are building a computational framework that analyzes immunofluorescence microscopy images of cells to identify alterations in individual pathways at a single-cell level. A primary novelty of our approach is a ``change of basis'' that allows us to understand signalling in cancer cells in terms of the much better understood patterns of signalling in normal cells. This allows us to model heterogeneous populations of cancer cells as a mixture of distinct subpopulations, each with a specific combination of signalling pathways altered beyond the normal baseline. We used this framework to analyze human bronchial epithelial cell lines containing a series of genetic modifications commonly seen in lung cancer. We confirmed expected trends (such as a population-wide epithelial mesenchymal transition following the last of our series of modifications) and are presently studying the relation between the mutational profiles of cancer cells and pathway crosstalk. Our framework will help establish a more natural basis for future investigations into the phenotype-genotype relationship in heterogeneous populations.

  2. Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

    PubMed Central

    Symonds, R Paul; Gourley, Charlie; Davidson, Susan; Carty, Karen; McCartney, Elaine; Rai, Debbie; Banerjee, Susana; Jackson, David; Lord, Rosemary; McCormack, Mary; Hudson, Emma; Reed, Nicholas; Flubacher, Maxine; Jankowska, Petra; Powell, Melanie; Dive, Caroline; West, Catharine M L; Paul, James

    2015-01-01

    Summary Background Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median

  3. 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

  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. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial

    PubMed Central

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

    2016-01-01

    Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59–74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81–1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour. PMID:27069473

  6. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

    PubMed

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

    2016-01-01

    Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.

  7. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

    PubMed

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

    2016-01-01

    Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour. PMID:27069473

  8. The muscle mass, omega-3, diet, exercise and lifestyle (MODEL) study – a randomised controlled trial for women who have completed breast cancer treatment

    PubMed Central

    2014-01-01

    Background Loss of lean body mass (LBM) is a common occurrence after treatment for breast cancer and is related to deleterious metabolic health outcomes [Clin Oncol, 22(4):281–288, 2010; Appl Physiol Nutr Metab, 34(5):950–956, 2009]. The aim of this research is to determine the effectiveness of long chain omega-3 fatty acids (LCn-3s) and exercise training alone, or in combination, in addressing LBM loss in breast cancer survivors. Methods/design A total of 153 women who have completed treatment for breast cancer in the last 12 months, with a Body Mass Index (BMI) of 20 to 35 kg/m2, will be randomly assigned to one of 3 groups: 3g/d LCn-3s (N-3), a 12-week nutrition and exercise education program plus olive oil (P-LC) or the education program plus LCn-3s (EX+N-3). Participants randomised to the education groups will be blinded to treatment, and will receive either olive oil placebo (OO+N-3) or LCn-3 provision, while the N-3 group will be open label. The education program includes nine 60-75min sessions over 12 weeks that will involve breast cancer specific healthy eating advice, plus a supervised exercise session run as a resistance exercise circuit. They will also be advised to conduct the resistance training and aerobic training 5 to 7 days per week collectively. Outcome measures will be taken at baseline, 12-weeks and 24-weeks. The primary outcome is % change in LBM as measured by the air displacement plethysmograhy. Secondary outcomes include quality of life (FACT-B + 4) and inflammation (C-Reactive protein: CRP). Additional measures taken will be erythrocyte fatty acid analysis, fatigue, physical activity, menopausal symptoms, dietary intake, joint pain and function indices. Discussion This research will provide the first insight into the efficacy of LCn-3s alone or in combination with exercise in breast cancer survivors with regards to LBM and quality of life. In addition, this study is designed to improve evidence-based dietetic practice, and how

  9. 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

  10. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial

    PubMed Central

    2008-01-01

    Summary Background The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. Methods Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. Findings 749 women were assigned to the 50 Gy group, 750 to the 41·6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5·1 years (IQR 4·4–6·0) the rate of local-regional tumour relapse at 5 years was 3·6% (95% CI 2·2–5·1) after 50 Gy, 3·5% (95% CI 2·1–4·3) after 41·6 Gy, and 5·2% (95% CI 3·5–6·9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2% (95% CI −1·3% to 2·6%) after 41·6 Gy and 0·9% (95% CI −0·8% to 3·7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in

  11. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group.

    PubMed Central

    1995-01-01

    OBJECTIVE--To evaluate the effect of cytotoxic chemotherapy on survival in patients with non-small cell lung cancer. DESIGN--Meta-analysis using updated data on individual patients from all available randomised trials, both published and unpublished. SUBJECTS--9387 patients (7151 deaths) from 52 randomised clinical trials. MAIN OUTCOME MEASURE--Survival. RESULTS--The results for modern regimens containing cisplatin favoured chemotherapy in all comparisons and reached conventional levels of significance when used with radical radiotherapy and with supportive care. Trials comparing surgery with surgery plus chemotherapy gave a hazard ratio of 0.87 (13% reduction in the risk of death, equivalent to an absolute benefit of 5% at five years). Trials comparing radical radiotherapy with radical radiotherapy plus chemotherapy gave a hazard ratio of 0.87 (13% reduction in the risk of death; absolute benefit of 4% at two years), and trials comparing supportive care with supportive care plus chemotherapy 0.73 (27% reduction in the risk of death; 10% improvement in survival at one year). The essential drugs needed to achieve these effects were not identified. No difference in the size of effect was seen in any subgroup of patients. In all but the radical radiotherapy setting, older trials using long term alkylating agents tended to show a detrimental effect of chemotherapy. This effect reached conventional significance in the adjuvant surgical comparison. CONCLUSION--At the outset of this meta-analysis there was considerable pessimism about the role of chemotherapy in non-small cell lung cancer. These results offer hope of progress and suggest that chemotherapy may have a role in treating this disease. PMID:7580546

  12. 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

  13. Single-blinded, randomised preliminary study evaluating the effects of 2 Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty

    PubMed Central

    Tzeng, Chung-Yuh; Chang, Shih-Liang; Wu, Chih-Cheng; Chang, Chu-Ling; Chen, Wen-Gii; Tong, Kwok-Man; Huang, Kui-Chou; Hsieh, Ching-Liang

    2015-01-01

    Objective To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA), Methods In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 (Zusanli) and GB34 (Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann–Whitney test was used to show the difference between two groups and the Kruskal–Wallis test to show the difference between the three groups. Results The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p<0.001) and 90.7±94.8 min in the NPG (p<0.001); there was no difference between the EAG and NPG groups (p>0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups. Conclusions In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen. PMID:25910930

  14. Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

    PubMed Central

    Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

    2015-01-01

    Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

  15. 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.

  16. 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

  17. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial

    PubMed Central

    Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus; Embleton, Andrew; Ledermann, Jonathan A; Pujade-Lauraine, Eric; Kristensen, Gunnar; Carey, Mark S; Beale, Philip; Cervantes, Andrés; Park-Simon, Tjoung-Won; Rustin, Gordon; Joly, Florence; Mirza, Mansoor R; Plante, Marie; Quinn, Michael; Poveda, Andrés; Jayson, Gordon C; Stark, Dan; Swart, Ann Marie; Farrelly, Laura; Kaplan, Richard; Parmar, Mahesh K B; Perren, Timothy J

    2015-01-01

    Summary Background The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. Methods ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I–IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb–IV), with an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Findings Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6–56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the

  18. Attitudes towards massage modify effects of manual therapy in breast cancer survivors: a randomised clinical trial with crossover design.

    PubMed

    Fernández-Lao, C; Cantarero-Villanueva, I; Díaz-Rodríguez, L; Cuesta-Vargas, A I; Fernández-Delas-Peñas, C; Arroyo-Morales, M

    2012-03-01

    Our aims were to investigate the immediate effect of myofascial release on heart rate variability and mood state, and the influence of attitude towards massage in breast cancer survivors with cancer-related fatigue. Twenty breast cancer survivors reporting moderate to high cancer-related fatigue participated in this crossover study. All patients presented to the laboratory at the same time of the day on two occasions separated by a 2-week interval. At each session, they received either a massage intervention or control intervention. Holter electrocardiogram recordings and Profile of Mood States questionnaire (six domains: tension-anxiety, depression-dejection, anger-hostility, vigour, fatigue, confusion) were obtained before and immediately after each intervention. The attitude towards massage scale was collected before the first session in all breast cancer survivors. The results showed a significant session × time interaction for standard deviation of the normal-to-normal interval (SDNN) (F= 5.063, P= 0.039), square root of mean squared differences of successive normal-to-normal intervals (RMSSD) (F= 8.273, P= 0.010), high-frequency component (HF) (F= 7.571, P= 0.013), but not for index heart rate variability (F= 3.451, P= 0.080), low-frequency component (LF) (F= 0.014, P= 0.997) and ratio LF/HF (F= 3.680, P= 0.072): significant increases in SDNN, RMSSD and HF domain (P < 0.05) were observed after the manual therapy intervention, with no changes after placebo (P > 0.6). No influence of the attitude scale on heart rate variability results was found. A significant session × time interaction was also found for fatigue (F= 5.101, P= 0.036) and disturbance of mood (F= 6.690, P= 0.018) scales of the Profile of Mood States: patients showed a significant decrease in fatigue and disturbance of mood (P < 0.001) after manual therapy, with no changes after placebo (P > 0.50). A significant influence of the attitude scale was observed in tension-anxiety, depression

  19. Single molecule targeted sequencing for cancer gene mutation detection.

    PubMed

    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. 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

  1. Birth after caesarean study – planned vaginal birth or planned elective repeat caesarean for women at term with a single previous caesarean birth: protocol for a patient preference study and randomised trial

    PubMed Central

    Dodd, Jodie M; Crowther, Caroline A; Hiller, Janet E; Haslam, Ross R; Robinson, Jeffrey S

    2007-01-01

    Background For women who have a caesarean section in their preceding pregnancy, two care policies for birth are considered standard: planned vaginal birth and planned elective repeat caesarean. Currently available information about the benefits and harms of both forms of care are derived from retrospective and prospective cohort studies. There have been no randomised trials, and recognising the deficiencies in the literature, there have been calls for methodologically rigorous studies to assess maternal and infant health outcomes associated with both care policies. The aims of our study are to assess in women with a previous caesarean birth, who are eligible in the subsequent pregnancy for a vaginal birth, whether a policy of planned vaginal birth after caesarean compared with a policy of planned repeat caesarean affects the risk of serious complications for the woman and her infant. Methods/Design Design: Multicentred patient preference study and a randomised clinical trial. Inclusion Criteria: Women with a single prior caesarean presenting in their next pregnancy with a single, live fetus in cephalic presentation, who have reached 37 weeks gestation, and who do not have a contraindication to a planned VBAC. Trial Entry & Randomisation: Eligible women will be given an information sheet during pregnancy, and will be recruited to the study from 37 weeks gestation after an obstetrician has confirmed eligibility for a planned vaginal birth. Written informed consent will be obtained. Women who consent to the patient preference study will be allocated their preference for either planned VBAC or planned, elective repeat caesarean. Women who consent to the randomised trial will be randomly allocated to either the planned vaginal birth after caesarean or planned elective repeat caesarean group. Treatment Groups: Women in the planned vaginal birth group will await spontaneous onset of labour whilst appropriate. Women in the elective repeat caesarean group will have this

  2. Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study.

    PubMed

    Mansi, Janine L; Yellowlees, Ann; Lipscombe, Julian; Earl, Helena M; Cameron, David A; Coleman, Robert E; Perren, Timothy; Gallagher, Christopher J; Quigley, Mary; Crown, John; Jones, Alison L; Highley, Martin; Leonard, Robert C F; Evans, T R Jeffry

    2010-08-01

    To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours > or = 3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) i/v or doxorubicin (50 mg/m(2)) plus docetaxel (75 mg/m(2)) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both disease-free and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

  3. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials

    PubMed Central

    Chang, Joe Y; Senan, Suresh; Paul, Marinus A; Mehran, Reza J; Louie, Alexander V; Balter, Peter; Groen, Harry J M; McRae, Stephen E; Widder, Joachim; Feng, Lei; van den Borne, Ben E E M; Munsell, Mark F; Hurkmans, Coen; Berry, Donald A; van Werkhoven, Erik; Kresl, John J; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J A; Carpenter, Larry S; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J; Smit, Egbert F; Roth, Jack A

    2015-01-01

    Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40.2 months (IQR 23.0–47.3) for the SABR group and 35.4 months (18.9–40.7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0.14 [95% CI 0.017–1.190], log-rank p=0.037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0.69 [95% CI 0.21–2.29], log-rank p=0.54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib

  4. 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

  5. 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

  6. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial

    PubMed Central

    Valle, Juan W; Wasan, Harpreet; Lopes, Andre; Backen, Alison C; Palmer, Daniel H; Morris, Karen; Duggan, Marian; Cunningham, David; Anthoney, D Alan; Corrie, Pippa; Madhusudan, Srinivasan; Maraveyas, Anthony; Ross, Paul J; Waters, Justin S; Steward, Will P; Rees, Charlotte; Beare, Sandy; Dive, Caroline; Bridgewater, John A

    2015-01-01

    Summary Background Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival. Methods In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK. Patients were eligible if they had an ECOG performance status of 0–1 and an estimated life expectancy of longer than 3 months. Patients were given first-line cisplatin and gemcitabine chemotherapy (25 mg/m2 cisplatin and 1000 mg/m2 gemcitabine [on days 1 and 8 every 21 days, for up to eight cycles]) with either 20 mg oral cediranib or placebo once a day until disease progression. We randomly assigned patients (1:1) with a minimisation algorithm, incorporating the stratification factors: extent of disease, primary disease site, previous treatment, ECOG performance status, and centre. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00939848, and was closed on Sept 30, 2014; results of the final analysis for the primary endpoint are presented. Findings Between April 5, 2011, and Sept 28, 2012, we enrolled 124 patients (62 in each group). With a median follow-up of 12·2 months (IQR 7·3–18·5), median progression-free survival was 8·0 months (95% CI 6·5–9·3) in the cediranib group and 7·4 months (5·7–8·5) in the placebo group (HR 0·93, 80% CI 0·74–1·19, 95% CI 0·65–1·35; p=0·72). Patients who received cediranib had more grade 3–4 toxic effects than did patients who received placebo: hypertension (23 [37%] vs

  7. 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

  8. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics

    PubMed Central

    Sculier, J P; Paesmans, M; Lecomte, J; Van Cutsem, O; Lafitte, J J; Berghmans, T; Koumakis, G; Florin, M C; Thiriaux, J; Michel, J; Giner, V; Berchier, M C; Mommen, P; Ninane, V; Klastersky, J

    2001-01-01

    The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m−2, vindesine 3 mg m−2, ifosfamide 5 g m−2; all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.   http://www.bjcancer.com PMID:11720426

  9. 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

  10. 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.

  11. 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.

  12. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial

    PubMed Central

    Paterson, Alexander H G; Anderson, Stewart J; Lembersky, Barry C; Fehrenbacher, Louis; Falkson, Carla I; King, Karen M; Weir, Lorna M; Brufsky, Adam M; Dakhil, Shaker; Lad, Thomas; Baez-Diaz, Luis; Gralow, Julie R; Robidoux, André; Perez, Edith A; Zheng, Ping; Geyer, Charles E; Swain, Sandra M; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

    2016-01-01

    Summary Background Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. Methods NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1–3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945. Findings Median follow-up was 90·7 months (IQR 82·7–100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78–1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67–1·05; p=0·13), recurrence-free interval (0·83, 0·67–1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55–1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55–1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57–0·99; p=0·045), bone metastasis-free interval (0·62, 0·40–0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43–0·91; p=0·014), but not for overall survival (0·80, 0·61–1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or

  13. INvolvement of breast CAncer patients during oncological consultations: a multicentre randomised controlled trial—the INCA study protocol

    PubMed Central

    Goss, Claudia; Ghilardi, Alberto; Deledda, Giuseppe; Buizza, Chiara; Bottacini, Alessandro; Del Piccolo, Lidia; Rimondini, Michela; Chiodera, Federica; Mazzi, Maria Angela; Ballarin, Mario; Bighelli, Irene; Strepparava, Maria Grazia; Molino, Annamaria; Fiorio, Elena; Nortilli, Rolando; Caliolo, Chiara; Zuliani, Serena; Auriemma, Alessandra; Maspero, Federica; Simoncini, Edda Lucia; Ragni, Fulvio; Brown, Richard; Zimmermann, Christa

    2013-01-01

    Introduction Studies on patient involvement show that physicians make few attempts to involve their patients who ask few questions if not facilitated. On the other hand, the patients who participate in the decision-making process show greater treatment adherence and have better health outcomes. Different methods to encourage the active participation during oncological consultation have been described; however, similar studies in Italy are lacking. The aims of the present study are to (1) assess the effects of a preconsultation intervention to increase the involvement of breast cancer patients during the consultation, and (2) explore the role of the attending companions in the information exchange during consultation. Methods and analysis All female patients with breast cancer who attend the Oncology Out-patient Services for the first time will provide an informed consent to participate in the study. They are randomly assigned to the intervention or to the control group. The intervention consists of the presentation of a list of relevant illness-related questions, called a question prompt sheet. The primary outcome measure of the efficacy of the intervention is the number of questions asked by patients during the consultation. Secondary outcomes are the involvement of the patient by the oncologist; the patient's perceived achievement of her information needs; the patient's satisfaction and ability to cope; the quality of the doctor–patient relationship in terms of patient-centeredness; and the number of questions asked by the patient's companions and their involvement during the consultation. All outcome measures are supposed to significantly increase in the intervention group. Ethics and dissemination The study was approved by the local Ethics Committee of the Hospital Trust of Verona. Study findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration ClinicalTrials.gov identifier: NCT01510964 PMID:23645911

  14. Formation of solid tumors by a single multinucleated cancer cel

    PubMed Central

    Weihua, Zhang; Lin, Qingtang; Ramoth, Asa J.; Fan, Dominic; Fidler, Isaiah J.

    2011-01-01

    BACKGROUND Large multinucleated cells (MNC) commonly exist in tumorigenic cancer cell lines widely used in research, but their contributions to tumorigenesis are unknown. METHODS In this study, we characterized MNCs in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at a single cell level. RESULTS We observed that MNCs originated from a rare subpopulation of mononuclear cells; MNCs were positive for a senescent marker, β-galacosidase (SA-β-Gal); MNCs were responsible for the majority of clonogenic activity when cultured in hard agar; MNCs were more resistant to chemotherapeutic agents than were mononuclear cells; MNCs could undergo asymmetric division (producing mononuclear cells) and self-renewal in vitro and in vivo; and, most importantly a single MNC produced orthotopic subcutaneous tumors (composed mainly of mononuclear cells) that gave rise to spontaneous lung metastases in nude mice. CONCLUSIONS MNCs can be growth-arrested under stress, are highly resistant to chemotherapy, and can generate clonal orthotopic metastatic tumors PMID:21365635

  15. 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

  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. 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

  18. 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

  19. 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.

  20. 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. PMID:27210845

  1. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

    PubMed Central

    Moriwaki, Toshikazu; Yamamoto, Yoshiyuki; Gosho, Masahiko; Kobayashi, Mariko; Sugaya, Akinori; Yamada, Takeshi; Endo, Shinji; Hyodo, Ichinosuke

    2016-01-01

    Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS). Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated. Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents. Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development. PMID:27031848

  2. 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

  3. 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.

  4. 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

  5. Cancer Prevalence among Physicians in Korea: A Single Center Study

    PubMed Central

    Kim, Hye Lin; Park, Hae Jin; Sim, Yun Hye; Choi, Eun Young; Shim, Kyung Won; Lee, Sang Wha; Lee, Hong Soo

    2016-01-01

    Background There is little research regarding whether working as a physician affects cancer risk. Moreover, there is no research on cancer prevalence among physicians in Korea. This study utilized the Korea National Cancer Incidence Database to determine whether the prevalence of cancer among physicians differs from the prevalence of cancer within the general population. Methods We analyzed the medical records of a representative sample of 382 doctors who underwent a health examination between 2010 and 2013 at a health examination center in a Ewha Womans University Medical Center.Cancer incidence was measured as cases that were eventually diagnosed as cancer according to a biopsy. Results We collected medical records from 382 physicians (mean age, 51.9±8.1 years) and calculated the standardized prevalence ratios compared to the general population. Thirty physicians (9 male and 21 female) were identified as having cancer. Physicians had a significantly higher prevalence of cancer compared to the general population.Cancer prevalence in male physicians was found to be 2.47 times higher than the prevalence expected within the general population (P=0.006). Among female physicians, cancer prevalence was 3.94 times higher than that in the general population (P<0.001). Conclusion This study revealed that physicians had a higher prevalence of cancer compared to the general population in Korea, which suggests that there may be a problem present in the health care of physicians. Changes to the working environment of physicians will be needed to reduce the high prevalence of cancer among physicians. PMID:27073607

  6. Prostate cancer marker panel with single cell sensitivity in urine

    PubMed Central

    Nickens, Kristen P.; Ali, Amina; Scoggin, Tatiana; Tan, Shyh‐Han; Ravindranath, Lakshmi; McLeod, David G.; Dobi, Albert; Tacha, David; Sesterhenn, Isabell A.; Srivastava, Shiv

    2015-01-01

    Background Over one million men undergo prostate biopsies annually in the United States, a majority of whom due to elevated serum PSA. More than half of the biopsies turn out to be negative for prostate cancer (CaP). The limitations of both the PSA test and the biopsy procedure have led to the development for more precise CaP detection assays in urine (e.g., PCA3, TMPRSS2‐ERG) or blood (e.g., PHI, 4K). Here, we describe the development and evaluation of the Urine CaP Marker Panel (UCMP) assay for sensitive and reproducible detection of CaP cells in post‐digital rectal examination (post‐DRE) urine. Methods The cellular content of the post‐DRE urine was captured on a translucent filter membrane, which is placed on Cytoclear slides for direct evaluation by microscopy and immuno‐cytochemistry (ICC). Cells captured on the membrane were assayed for PSA and Prostein expression to identify prostate epithelial cells, and for ERG and AMACR to identify prostate tumor cells. Immunostained cells were analyzed for quantitative and qualitative features and correlated with biopsy positive and negative status for malignancy. Results The assay was optimized for single cell capture sensitivity and downstream evaluations by spiking a known number of cells from established CaP cell lines, LNCaP and VCaP, into pre‐cleared control urine. The cells captured from the post‐DRE urine of subjects, obtained prior to biopsy procedure, were co‐stained for ERG, AMACR (CaP specific), and Prostein or PSA (prostate epithelium specific) rendering a whole cell based analysis and characterization. A feasibility cohort of 63 post‐DRE urine specimens was assessed. Comparison of the UCMP results with blinded biopsy results showed an assay sensitivity of 64% (16 of 25) and a specificity of 68.8% (22 of 32) for CaP detection by biopsy. Conclusions This pilot study assessing a minimally invasive CaP detection assay with single cell sensitivity cell‐capture and characterization from the

  7. Duration of cortisol suppression following a single dose of dexamethasone in healthy volunteers: a randomised double-blind placebo-controlled trial.

    PubMed

    Elston, M S; Conaglen, H M; Hughes, C; Tamatea, J A U; Meyer-Rochow, G Y; Conaglen, J V

    2013-09-01

    The synthetic glucocorticoid dexamethasone is administered to many patients receiving a general anaesthetic to reduce the risk of postoperative nausea and vomiting. Dexamethasone is known to suppress the hypothalamic-pituitary-adrenal axis; however, the duration of this suppression following the standard anti-emetic intravenous dose of 4 to 8 mg used with anaesthesia is unknown. A randomised controlled double-blind crossover trial assessing the effects of 8 mg intravenous dexamethasone versus saline control was performed in ten healthy male volunteers. The adrenal, thyroid and gonadal axes and glucose levels were assessed over a four-day period after dexamethasone administration. All participants had normal baseline hypothalamic-pituitary-adrenal axis function. No difference in cortisol levels was demonstrated at four or eight hours after dexamethasone administration compared with placebo. At 24 hours post dexamethasone, the cortisol had dropped to less than 5% of baseline and returned to normal during the subsequent day. Increased plasma glucose levels were also observed in the dexamethasone group as compared with placebo. A dose of 8 mg of dexamethasone results in significant suppression of the hypothalamic-pituitary-adrenal axis and elevated plasma glucose levels. The cortisol suppression is maximal at approximately 24 hours post dose.

  8. 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

  9. Sequential or alternating administration of docetaxel (Taxotere®) combined with FEC in metastatic breast cancer: a randomised phase II trial

    PubMed Central

    Spielmann, M; Tubiana-Hulin, M; Namer, M; Mansouri, H; Bougnoux, P h; Tubiana-Mathieu, N; Lotz, V; Eymard, J C

    2002-01-01

    The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere® 100 mg m−2 docetaxel and FEC 75 cyclophosphamide 500 mg m−2, fluorouracil 500 mg m−2 and epirubicin 75 mg m−2, in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3–4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (⩽9%) developed grade 3–4 non-haematological toxicities. Relative dose intensity was 97–99% for all regimens. All treatment regimens were active and well tolerated. British Journal of Cancer (2002) 86, 692–697. DOI: 10.1038/sj/bjc/6600165 www.bjcancer.com © 2002 Cancer Research UK PMID:11875727

  10. The Convergent Cancer Evolution toward a Single Cellular Destination.

    PubMed

    Chen, Han; He, Xionglei

    2016-01-01

    The essence of Darwin's theory is that evolution is driven by purposeless mutations that are subsequently selected by natural environments, so there is often no predefined destination in organismal evolution. Using gene expressions of 107 cell types, we built a functional space of human cells to trace the evolutionary trajectory of 18 types of solid tumor cancers. We detected a dominant evolving trend toward the functional status of embryonic stem cells (ESC) for approximately 3,000 tumors growing in distinct tissue environments. This pattern remained the same after excluding known cancer/ESC signature genes (∼ 3,000 genes) or excluding all oncogenic gene sets (∼ 12,000 genes) annotated in MSigDB, suggesting a convergent evolution of the overall functional status in cancers. In support of this, the functional distance to ESC served as a common prognostic indicator for cancers of various types, with shorter distance corresponding to poor prognosis, which was true even when randomly selected gene sets were considered. Thus, regardless of the external environments, cancer evolution is a directional process toward a defined cellular destination, a finding reconciling development and evolution, the two seemingly incompatible philosophies both adopted by the cancer research community, and also raising new questions to evolutionary biology.

  11. 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

  12. Rationale, design, and implementation protocol of the Dutch clinical practice guideline Pain in patients with cancer: a cluster randomised controlled trial with short message service (SMS) and interactive voice response (IVR)

    PubMed Central

    2011-01-01

    Background One-half of patients with cancer have pain. In nearly one out of two cancer patients with pain, this was undertreated. Inadequate pain control still remains an important problem in this group of patients. Therefore, in 2008 a national, evidence-based multidisciplinary clinical practice guideline 'pain in patients with cancer' has been developed. Yet, publishing a guideline is not enough. Implementation is needed to improve pain management. An innovative implementation strategy, Short Message Service with Interactive Voice Response (SVS-IVR), has been developed and pilot tested. This study aims to evaluate on effectiveness of this strategy to improve pain reporting, pain measurement and adequate pain therapy. In addition, whether the active role of the patient and involvement of caregivers in pain management may change. Methods/design A cluster randomised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherlands, with three hospitals in the intervention and three in the control condition. Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention. The intervention includes training of professionals (medical oncologists, nurses, and general practitioners) and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients, pain management by medical oncologists, nurses, and general practitioners, and decrease pain intensity. Discussion This innovative implementation strategy with technical tools and the involvement of patients, may enhance the use of the guideline 'pain in patients with cancer' for pain management. Short Message Service alerts may serve as a tool to support self-management of patients. Therefore, the SMS-IVR intervention may increase the feeling of having control over one's life. Trail registration Netherlands Trial Register (NTR): NTR2739 PMID:22142327

  13. Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial

    PubMed Central

    Green, Jonathan; Charman, Tony; Pickles, Andrew; Wan, Ming W; Elsabbagh, Mayada; Slonims, Vicky; Taylor, Carol; McNally, Janet; Booth, Rhonda; Gliga, Teodora; Jones, Emily J H; Harrop, Clare; Bedford, Rachael; Johnson, Mark H

    2015-01-01

    Summary Background Risk markers for later autism identified in the first year of life present plausible intervention targets during early development. We aimed to assess the effect of a parent-mediated intervention for infants at high risk of autism on these markers. Methods We did a two-site, two-arm assessor-blinded randomised controlled trial of families with an infant at familial high risk of autism aged 7–10 months, testing the adapted Video Interaction to Promote Positive Parenting (iBASIS-VIPP) versus no intervention. Families were randomly assigned to intervention or no intervention groups using a permuted block approach stratified by centre. Assessors, but not families or therapists, were masked to group assignment. The primary outcome was infant attentiveness to parent. Regression analysis was done on an intention-to-treat basis. This trial is registered with ISCRTN Registry, number ISRCTN87373263. Findings We randomly assigned 54 families between April 11, 2011, and Dec 4, 2012 (28 to intervention, 26 to no intervention). Although CIs sometimes include the null, point estimates suggest that the intervention increased the primary outcome of infant attentiveness to parent (effect size 0·29, 95% CI −0·26 to 0·86, thus including possibilities ranging from a small negative treatment effect to a strongly positive treatment effect). For secondary outcomes, the intervention reduced autism-risk behaviours (0·50, CI −0·15 to 1·08), increased parental non-directiveness (0·81, 0·28 to 1·52), improved attention disengagement (0·48, −0·01 to 1·02), and improved parent-rated infant adaptive function (χ2[2] 15·39, p=0·0005). There was a possibility of nil or negative effect in language and responsivity to vowel change (P1: ES–0·62, CI −2·42 to 0·31; P2: −0·29, −1·55 to 0·71). Interpretation With the exception of the response to vowel change, our study showed positive estimates across a wide range of behavioural and brain function

  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. Diagnosis of colorectal cancer using Raman spectroscopy of laser-trapped single living epithelial cells

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Qin, Yejun; Zheng, Feng; Sun, Menghong; Shi, Daren

    2006-07-01

    A single-cell diagnostic technique for epithelial cancers is developed by utilizing laser trapping and Raman spectroscopy to differentiate cancerous and normal epithelial cells. Single-cell suspensions were prepared from surgically removed human colorectal tissues following standard primary culture protocols and examined in a near-infrared laser-trapping Raman spectroscopy system, where living epithelial cells were investigated one by one. A diagnostic model was built on the spectral data obtained from 8 patients and validated by the data from 2 new patients. Our technique has potential applications from epithelial cancer diagnosis to the study of cell dynamics of carcinogenesis.

  16. 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

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

    PubMed

    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

    2013-12-24

    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.

  18. 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

  19. 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

  20. 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

  1. Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal.

    PubMed

    Whyte, Sophie; Pandor, Abdullah; Stevenson, Matt

    2012-12-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of bevacizumab (Roche Products) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with metastatic colorectal cancer (mCRC), as part of the Institute's Single Technology Appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology provided within the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a phase III, multicentre, multinational, two-arm, randomized, open-label study with the primary objective of confirming the non-inferiority of oxaliplatin plus capecitabine (XELOX) compared with oxaliplatin plus 5-fluorouracil and folinic acid (FOLFOX-4) in adult patients with histologically confirmed mCRC who had not previously been treated. The ERG considered that the NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free and overall survival when bevacizumab is added to either XELOX or FOLFOX-4. The ERG considered that the size of the actual treatment effect of bevacizumab was uncertain due to trial design limitations, imbalance of a known prognostic factor, relatively short treatment duration compared with that allowed within the trial protocol, and interpretation of the statistical analyses. The manufacturer's submission included a de novo economic evaluation using a cost-effectiveness model built in Microsoft® Excel. The ERG

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

    PubMed

    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

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

    PubMed

    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.

  4. 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

  5. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25907226

  7. 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.

  8. Polyphenol- and fibre-rich dried fruits with green tea attenuate starch-derived postprandial blood glucose and insulin: a randomised, controlled, single-blind, cross-over intervention.

    PubMed

    Nyambe-Silavwe, H; Williamson, G

    2016-08-01

    Polyphenol- and fibre-rich foods (PFRF) have the potential to affect postprandial glycaemic responses by reducing glucose absorption, and thus decreasing the glycaemic response of foods when consumed together. A randomised, single-blind, cross-over study was conducted on sixteen healthy volunteers to test whether PFRF could attenuate postprandial blood glucose in healthy volunteers when added to a source of carbohydrate (starch in bread). This is the first study to examine the effects of a meal comprised of components to inhibit each stage of the biochemical pathway, leading up to the appearance of glucose in the blood. The volunteers were fasted and attended four visits: two control visits (bread, water, balancing sugars) and two test visits (single and double dose of PFRF) where they consumed bread, water and PFRF. Blood samples were collected at 0 (fasted), 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption. The PFRF components were tested for α-amylase and α-glucosidase inhibitory potential in vitro. Plasma glucose was lower after consumption of both doses compared with controls: lower dose, change in mean incremental areas under the glucose curves (IAUC)=-27·4 (sd 7·5) %, P<0·001; higher dose, IAUC=-49·0 (sd 15·3) %, P<0·001; insulin IAUC was also attenuated by-46·9 (sd 13·4) %, P<0·01. Consistent with this, the polyphenol components of the PFRF inhibited α-amylase (green tea, strawberry, blackberry and blackcurrant) and α-glucosidase (green tea) activities in vitro. The PFRF have a pronounced and significant lowering effect on postprandial blood glucose and insulin response in humans, due in part to inhibition of α-amylase and α-glucosidase, as well as glucose transport. PMID:27278405

  9. Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

    PubMed Central

    Khalil, Eltahir A. G.; Weldegebreal, Teklu; Younis, Brima M.; Omollo, Raymond; Musa, Ahmed M.; Hailu, Workagegnehu; Abuzaid, Abuzaid A.; Dorlo, Thomas P. C.; Hurissa, Zewdu; Yifru, Sisay; Haleke, William; Smith, Peter G.; Ellis, Sally; Balasegaram, Manica; EL-Hassan, Ahmed M.; Schoone, Gerard J.; Wasunna, Monique; Kimutai, Robert; Edwards, Tansy; Hailu, Asrat

    2014-01-01

    Background Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. Methodology A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. Principal Findings The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. Conclusions The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. Trials Registration www.clinicaltrials.gov NCT00832208 PMID:24454970

  10. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial

    PubMed Central

    Patz, Edward F; Greco, Erin; Gatsonis, Constantine; Pinsky, Paul; Kramer, Barnett S; Aberle, Denise R

    2016-01-01

    Summary Background Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. Methods We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55–74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385. Findings Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97–408·26] per 100 000 person-years vs 661·23 [622·07–702·21]) and had lower lung cancer

  11. Single-Nucleotide Polymorphism to Associate Cancer Risk.

    PubMed

    Shaw, Victoria; Bullock, Katie; Greenhalf, William

    2016-01-01

    Genetic heterogeneity explains variation in predisposition for cancer. Whole-genome analysis allows risk to be quantified, giving better targeted screening and quantification of the personalized risk posed by environmental factors. Array-based approaches to whole-genome analysis are rapidly being overtaken by next-generation sequencing (NGS). In this review the different platforms currently available for NGS are compared and the opportunities and risks of this approach are discussed: including the informatics packages required and the ethical issues. Methods applicable to the personal genome machine (PGM) are given as an example of workflows.

  12. Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression

    PubMed Central

    Kim, Min Su; Lee, Ha Na; Kim, Hae Jong; Myung, Soon Chul

    2015-01-01

    ABSTRACT We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02–0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author's knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors. PMID:26689513

  13. 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

  14. Down's syndrome-associated Single Minded 2 gene as a pancreatic cancer drug therapy target.

    PubMed

    DeYoung, Maurice Phil; Tress, Matthew; Narayanan, Ramaswamy

    2003-10-01

    We report here a pancreatic cancer drug therapy utility of a gene involved in Down's syndrome. Single Minded 2 gene (SIM2) from Down's Syndrome Critical Region was expressed in pancreatic cancer-derived cell lines as well as in tumor tissues, but not in the normal pancreas. A related member of the SIM family, SIM1, did not show similar specificity. Inhibition by antisense technology of one of the isoforms of SIM2, the short-form (SIM2-s) expression in the CAPAN-1 pancreatic cancer cell line, caused a pronounced growth inhibition and induced cell death through apoptosis. The specificity of antisense was inferred from inhibition of SIM2-s mRNA but not the related members of SIM family. In view of the high mortality rate of pancreatic cancer patients, these findings have important implications for the future of pancreatic cancer treatment.

  15. A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer.

    PubMed

    Liu, Ben; Zhang, Xining; Song, Fengju; Liu, Qun; Dai, Hongji; Zheng, Hong; Cui, Ping; Zhang, Lina; Zhang, Wei; Chen, Kexin

    2016-06-01

    A single-nucleotide polymorphism (SNP) locus rs16917496 (T > C) within the 3'-untranslated region (3'-UTR) of SET8 was associated with susceptibility in several malignancies including breast cancer. To further elucidate the prognostic relevance of this SNP in breast cancer, we conducted a clinical study as well as SET8 expression analysis in a cohort of 1,190 breast cancer patients. We demonstrated the expression levels of SET8 in TT genotype were higher than in CC genotypes, and high levels of SET8 were associated with poor survival. SET8 expression was significantly higher in breast tumor tissue than in paired adjacent normal tissue. In addition, survival analysis in 315 patients showed SNP rs16917496 was an independent prognostic factor of breast cancer outcome with TT genotype associated with poor survival compared with CC/CT genotypes. Thus, this SNP may serve as a genetic prognostic factor and a treatment target for breast cancer. Future studies are warranted.

  16. Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial

    PubMed Central

    Colombo, N; McMeekin, D S; Schwartz, P E; Sessa, C; Gehrig, P A; Holloway, R; Braly, P; Matei, D; Morosky, A; Dodion, P F; Einstein, M H; Haluska, F

    2013-01-01

    Background: This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer. Methods: Women with measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more. Results: In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%). Conclusion: Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted. PMID:23403817

  17. SUCCINCT: An Open-label, Single-arm, Non-randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-line Treatment for Patients with Advanced Urothelial Carcinoma

    PubMed Central

    Geldart, Thomas; Chester, John; Casbard, Angela; Crabb, Simon; Elliott, Tony; Protheroe, Andrew; Huddart, Robert A.; Mead, Graham; Barber, Jim; Jones, Robert J.; Smith, Joanna; Cowles, Robert; Evans, Jessica; Griffiths, Gareth

    2015-01-01

    Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2–15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40–63%) were progression free. Median overall survival was 12 mo (95% CI, 9–15) and was heavily influenced by Bajorin prognostic group. Grade 3–4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended. Patient summary The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity. PMID:25465968

  18. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine†

    PubMed Central

    Montgomery, Stuart A; Nielsen, Rebecca Z; Poulsen, Lis H; Häggström, Lars

    2014-01-01

    Objective This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine (10–20 mg/day) versus agomelatine (25–50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin–noradrenaline reuptake inhibitor (SNRI) monotherapy. Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms (Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life (EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale). Results Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p < 0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence. Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated. PMID:25087600

  19. Does a strategy to promote shared decision-making reduce medical practice variation in the choice of either single or double embryo transfer after in vitro fertilisation? A secondary analysis of a randomised controlled trial

    PubMed Central

    Brabers, Anne E M; van Dijk, Liset; Groenewegen, Peter P; van Peperstraten, Arno M; de Jong, Judith D

    2016-01-01

    Objectives The hypothesis that shared decision-making (SDM) reduces medical practice variations is increasingly common, but no evidence is available. We aimed to elaborate further on this, and to perform a first exploratory analysis to examine this hypothesis. This analysis, based on a limited data set, examined how SDM is associated with variation in the choice of single embryo transfer (SET) or double embryo transfer (DET) after in vitro fertilisation (IVF). We examined variation between and within hospitals. Design A secondary analysis of a randomised controlled trial. Setting 5 hospitals in the Netherlands. Participants 222 couples (woman aged <40 years) on a waiting list for a first IVF cycle, who could choose between SET and DET (ie, ≥2 embryos available). Intervention SDM via a multifaceted strategy aimed to empower couples in deciding how many embryos should be transferred. The strategy consisted of decision aid, support of IVF nurse and the offer of reimbursement for an extra treatment cycle. Control group received standard IVF care. Outcome measure Difference in variation due to SDM in the choice of SET or DET, both between and within hospitals. Results There was large variation in the choice of SET or DET between hospitals in the control group. Lower variation between hospitals was observed in the group with SDM. Within most hospitals, variation in the choice of SET or DET appeared to increase due to SDM. Variation particularly increased in hospitals where mainly DET was chosen in the control group. Conclusions Although based on a limited data set, our study gives a first insight that including patients’ preferences through SDM results in less variation between hospitals, and indicates another pattern of variation within hospitals. Variation that results from patient preferences could be potentially named the informed patient rate. Our results provide the starting point for further research. Trial registration number NCT00315029; Post-results. PMID

  20. Effects of an exercise and manual therapy program on physical impairments, function and quality-of-life in people with osteoporotic vertebral fracture: a randomised, single-blind controlled pilot trial

    PubMed Central

    2010-01-01

    Background This randomised, single-blind controlled pilot trial aimed to determine the effectiveness of a physiotherapy program, including exercise and manual therapy, in reducing impairments and improving physical function and health-related quality of life in people with a history of painful osteoporotic vertebral fracture. Methods 20 participants were randomly allocated to an intervention (n = 11) or control (n = 9) group. The intervention group attended individual sessions with an experienced clinician once a week for 10 weeks and performed daily home exercises with adherence monitored by a self-report diary. The control group received no treatment. Blinded assessment was conducted at baseline and 11 weeks. Questionnaires assessed self-reported changes in back pain, physical function, and health-related quality of life. Objective measures of thoracic kyphosis, back and shoulder muscle endurance (Timed Loaded Standing Test), and function (Timed Up and Go test) were also taken. Results Compared with the control group, the intervention group showed significant reductions in pain during movement (mean difference (95% CI) -1.8 (-3.5 to -0.1)) and at rest (-2.0 (-3.8 to -0.2)) and significantly greater improvements in Qualeffo physical function (-4.8 (-9.2 to -0.5)) and the Timed Loaded Standing test (46.7 (16.1 to 77.3) secs). For the perceived change in back pain over the 10 weeks, 9/11 (82%) participants in the intervention group rated their pain as 'much better' compared with only 1/9 (11%) participants in the control group. Conclusion Despite the modest sample size, these results support the benefits of exercise and manual therapy in the clinical management of patients with osteoporotic vertebral fractures, but need to be confirmed in a larger sample. Trail registration NCT00638768 PMID:20163739

  1. 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

  2. Prevention of surgical site infection in lower limb skin lesion excisions with single dose oral antibiotic prophylaxis: a prospective randomised placebo-controlled double-blind trial

    PubMed Central

    Smith, Samuel C; Heal, Clare F; Buttner, Petra G

    2014-01-01

    Objectives To determine the effectiveness of a single perioperative prophylactic 2 g dose of cephalexin in preventing surgical site infection (SSI) following excision of skin lesions from the lower limb. Design Prospective double-blinded placebo-controlled trial testing for difference in infection rates. Setting Primary care in regional North Queensland, Australia. Participants 52 patients undergoing lower limb skin lesion excision. Interventions 2 g dose of cephalexin 30–60 min before excision. Main outcome measures Incidence of SSI. Results Incidence of SSI was 12.5% (95% CI 2.7% to 32.4%) in the cephalexin group compared with 35.7% (95% CI 18.6% to 55.9%) in the placebo group (p=0.064). This represented an absolute reduction of 23.21% (95% CI −0.39% to 46.82%), relative reduction of 65.00% (95% CI −12.70% to 89.13%) and number-needed-to-treat of 4.3. Conclusions Administration of a single 2 g dose of cephalexin 30–60 min before skin lesion excision from the lower limb may produce a reduction in the incidence of infection; however, this study was underpowered to statistically determine this. Trial registration number ACTRN12611000595910. PMID:25079934

  3. Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research

    PubMed Central

    2013-01-01

    Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing approaches for directly elucidating phosphoprotein signaling networks in cancer cells or for capturing high-resolution snapshots of immune system function in patients with various disease conditions. We discuss advances in single-cell proteomics platforms, with an emphasis on microchip methods. These methods can provide a direct correlation of morphological, functional and molecular signatures at the single-cell level. We also provide examples of how those platforms are being applied to both fundamental biology and clinical studies, focusing on immune-system monitoring and phosphoprotein signaling networks in cancer. PMID:23998271

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

    PubMed

    Chéry, Lisly; Lam, Hung-Ming; 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

    2014-10-30

    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.

  5. Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients.

    PubMed

    Veronesi, U; Salvadori, B; Luini, A; Greco, M; Saccozzi, R; del Vecchio, M; Mariani, L; Zurrida, S; Rilke, F

    1995-09-01

    Breast conservation has become well-established in the treatment of early mammary carcinoma. However, a standardised treatment modality has not emerged. We have analysed the data from 1,973 patients treated in three consecutive randomised trials by four different radiosurgical procedures: Halsted mastectomy, quadrantectomy plus radiotherapy, lumpectomy plus radiotherapy, and quadrantectomy without radiotherapy, to compare the outcomes of these procedures in terms of local recurrence rate and overall survival. Eligibility criteria were similar in the three trials, and comparability between the four subgroups was excellent. Median follow-up for all patients was 82 months. The annual rates of local recurrence varied markedly according to the treatment. Patients treated with Halsted mastectomy and quadrantectomy plus radiotherapy had low annual rates of local recurrence (0.20 and 0.46, respectively) while both lumpectomy plus radiotherapy and quadrantectomy without radiotherapy had significantly higher rates (2.45 and 3.28, respectively). Patients under 45 years of age had a much higher incidence of local recurrences, while in women over 55 years local recurrences were much less frequent. Overall survival curves were identical in the four groups of patients, so that the three breast conserving radiosurgical procedures had the same survival rates as Halsted mastectomy. However, local recurrence rates were markedly influenced by the treatment method, patient age and specific histological features.

  6. Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer

    PubMed Central

    Galardi, Francesca; Pestrin, Marta; Gabellini, Stefano; Simi, Lisa; Mancini, Irene; Vannucchi, Alessandro Maria; Pazzagli, Mario; Di Leo, Angelo; Pinzani, Pamela

    2016-01-01

    Circulating Tumor Cells (CTCs) represent a “liquid biopsy” of the tumor potentially allowing real-time monitoring of cancer biology and therapies in individual patients. The purpose of the study was to explore the applicability of a protocol for the molecular characterization of single CTCs by Next Generation Sequencing (NGS) in order to investigate cell heterogeneity and provide a tool for a personalized medicine approach. CTCs were enriched and enumerated by CellSearch in blood from four metastatic breast cancer patients and singularly isolated by DEPArray. Upon whole genome amplification 3–5 single CTCs per patient were analyzed by NGS for 50 cancer-related genes. We found 51 sequence variants in 25 genes. We observed inter- and intra-patient heterogeneity in the mutational status of CTCs. The highest number of somatic deleterious mutations was found in the gene TP53, whose mutation is associated with adverse prognosis in breast cancer. The discordance between the mutational status of the primary tumor and CTCs observed in 3 patients suggests that, in advanced stages of cancer, CTC characteristics are more closely linked to the dynamic modifications of the disease status. In one patient the mutational profiles of CTCs before and during treatment shared only few sequence variants. This study supports the applicability of a non-invasive approach based on the liquid biopsy in metastatic breast cancer patients which, in perspective, should allow investigating the clonal evolution of the tumor for the development of new therapeutic strategies in precision medicine. PMID:27034166

  7. A randomised, single blinded trial, assessing the effect of a two week preoperative very low calorie diet on laparoscopic cholecystectomy in obese patients

    PubMed Central

    Burnand, Katherine M.; Lahiri, Rajiv P.; Burr, Nicholas; Jansen van Rensburg, Lize; Lewis, Michael P.N.

    2016-01-01

    Background Laparoscopic cholecystectomy (LC) can be technically challenging in the obese. The primary aim of the trial was to establish whether following a Very Low Calorie Diet (VLCD) for two weeks pre-operatively reduces operation time. Secondary outcomes included perceived operative difficulty and length of hospital stay. Methods A single-blinded, randomized controlled trial of consecutive patients with symptomatic gallstones and BMI >30 kg/m2 46 patients were randomized to a VLCD or normal diet for two weeks prior to LC. Food diaries were used to document dietary intake. The primary outcome measure was operation time. Secondary outcomes were length of stay, weight change operative complications, day case rates and perceived difficulty of operation. Results The VLCD was well tolerated and had significantly greater preoperative weight loss (3.48 kg vs. 0.98 kg; p < 0.0001). Median operative time was significantly reduced by 6 min in the VLCD group (25 vs. 31 min; p = 0.0096). There were no differences in post-operative complications, length of stay, or day case rates between the groups. Dissection of Calot's triangle was deemed significantly easier in the VLCD group. Conclusion A two week VLCD prior to elective laparoscopic cholecystectomy in obese patients is safe, well tolerated and was shown to significantly reduce pre-operative weight and operative time. Trial registration ISRCTN: 61630192. http://www.isrctn.com/ISRCTN61630192 Trial registration. PMID:27154810

  8. The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party.

    PubMed Central

    Stephens, R. J.; Girling, D. J.; Bleehen, N. M.; Moghissi, K.; Yosef, H. M.; Machin, D.

    1996-01-01

    The role of post-operative radiotherapy for patients with non-small-cell lung cancer (NSCLC) is unclear despite five previous randomised trials. One deficiency with these trials was that they did not include adequate TNM staging, and so the present randomised trial was designed to compare surgery alone (S) with surgery plus post-operative radiotherapy (SR) in patients with pathologically staged T1-2, N1-2. M0 NSCLC. Between July 1986 and October 1993, 308 patients (154 S, 154 SR) were entered from 16 centres in the UK. The median age of the patients was 62 years, 74% were male, > 85% had normal or near normal levels of general condition, activity and breathlessness, 68% had squamous carcinoma, 52% had had a pneumonectomy, 63% had N1 disease and 37% N2 disease. SR patients received 40 Gy in 15 fractions starting 4-6 weeks post-operatively. Overall there was no advantage to either group in terms of survival, although definite local recurrence and bony metastases appeared less frequently and later in the SR group. In a subgroup analysis, in the N1 group no differences between the treatment groups were seen, but in the N2 group SR patients appeared to gain a one month survival advantage, delayed time to local recurrence and time to appearance of the bone metastases. There is, therefore, no clear indication for post-operative radiotherapy in N1 disease, but the question remains unresolved in N2 disease. PMID:8761382

  9. Randomised, phase II, placebo-controlled, trial of fulvestrant plus vandetanib in postmenopausal women with bone only or bone predominant, hormone-receptor-positive metastatic breast cancer (MBC): the OCOG ZAMBONEY study.

    PubMed

    Clemons, Mark J; Cochrane, Brandy; Pond, Gregory R; Califaretti, Nadia; Chia, Stephen K L; Dent, Rebecca Alexandra; Song, Xinni; Robidoux, Andre; Parpia, Sameer; Warr, David; Rayson, Daniel; Pritchard, Kathleen I; Levine, Mark N

    2014-07-01

    Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used as surrogate measures of response to bone-targeted therapies. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases. We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in breast cancer patients with bone metastases. Postmenopausal patients with bone predominant, hormone-receptor-positive metastatic breast cancer were randomised to F (500 mg IM days 1, 15, 29, then monthly) with either vandetanib (100 mg PO OD) (FV) or placebo (FP). The primary objective was uNTx response. Secondary objectives included PFS, OS, RECIST response, pain scores and toxicity. Sixty-one patients were allocated to FV and 68 to FP. Out of 127 analyzable patients, an uNTx response occurred in 66 % for FV and 54 % for FP (p = 0.21). No difference was detected between groups for PFS; HR = 0.95 (95 % CI 0.65-1.38) or OS HR = 0.69 (95 % CI 0.37-1.31). For the 62 patients with measurable disease, clinical benefit rates were 41 and 43 %, respectively (p = 0.47). Serious adverse events were similar, 3.3 % for FV versus 5.9 % for FP. Elevated baseline uNTx (>65 nM BCE/mmol Cr) was prognostic for PFS, HR = 1.55 (95 % CI 1.04-2.30) and for OS, HR = 2.32 (95 % CI 1.25-4.33). The addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS. PMID:24924416

  10. 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. PMID:23901300

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

    PubMed Central

    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. PMID:23901300

  12. Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial.

    PubMed

    Reid, Marie; Hammersley, Richard; Duffy, Maresa; Ballantyne, Carrie

    2014-02-01

    To investigate whether obese women can compensate for sucrose added to the diet when it is given blind, rather than gaining weight or exhibiting dysfunctional regulation of intake, in the present study, forty-one healthy obese (BMI 30-35 kg/m²) women (age 20-50 years), not currently dieting, were randomly assigned to consume sucrose (n 20) or aspartame (n 21) drinks over 4 weeks in a parallel single-blind design. Over the 4 weeks, one group consumed 4 × 250 ml sucrose drinks (total 1800 kJ/d) and the other group consumed 4 × 250 ml aspartame drinks. During the baseline week and experimental weeks, body weight and other biometric data were measured and steps per day, food intake using 7 d unweighed food diaries, and mood using ten- or seven-point Likert scales four times a day were recorded. At the end of the experiment, the participants weighed 1·72 (SE 0·47) kg less than the value predicted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) model; the predicted body weight accounted for 94·3% of the variance in the observed body weight and experimental group accounted for a further 1·1% of the variance in the observed body weight, showing that women consuming sucrose drinks gained significantly less weight than predicted. The reported daily energy intake did not increase significantly, and sucrose supplements significantly reduced the reported voluntary sugar, starch and fat intake compared with aspartame. There were no effects on appetite or mood. Over 4 weeks, as part of everyday eating, sucrose given blind in soft drinks was partially compensated for by obese women, as in previous experiments with healthy and overweight participants.

  13. Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study

    PubMed Central

    2014-01-01

    Background Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. Methods/Design Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. Discussion Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We

  14. The first five years of single-cell cancer genomics and beyond.

    PubMed

    Navin, Nicholas E

    2015-10-01

    Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five years, there has been extraordinary progress in technological developments and research applications, but these efforts represent only the tip of the iceberg. In the coming years, SCS will greatly improve our understanding of invasion, metastasis, and therapy resistance during cancer progression. These tools will also have direct translational applications in the clinic, in areas such as early detection, noninvasive monitoring, and guiding targeted therapy. In this perspective, I discuss the progress that has been made and the myriad of unexplored applications that still lie ahead in cancer research and medicine. PMID:26430160

  15. The first five years of single-cell cancer genomics and beyond.

    PubMed

    Navin, Nicholas E

    2015-10-01

    Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five years, there has been extraordinary progress in technological developments and research applications, but these efforts represent only the tip of the iceberg. In the coming years, SCS will greatly improve our understanding of invasion, metastasis, and therapy resistance during cancer progression. These tools will also have direct translational applications in the clinic, in areas such as early detection, noninvasive monitoring, and guiding targeted therapy. In this perspective, I discuss the progress that has been made and the myriad of unexplored applications that still lie ahead in cancer research and medicine.

  16. Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility.

    PubMed

    Murali, Abitha; Nalinakumari, K R; Thomas, Shaji; Kannan, S

    2014-09-01

    Alterations in the regulation of the cell cycle are strongly linked to tumorigenesis, so genetic variants in genes critical to control of the cycle are good candidates to have their association with susceptibility to oral cancer assessed. In this hospital-based, case-control study of 445 patients who had been newly-diagnosed with oral cancer and 449 unaffected controls, we used a multigenic approach to examine the associations among a panel of 10 selected polymorphisms in the pathway of the cell cycle that were possibly susceptible to oral cancer. Six of 9 single nucleotide polymorphisms in the cell cycle showed significant risks for oral cancer, the highest risk being evident for p27 (rs34329; Odds ratio 3.05, 95% CI 2.12 to 4.40). A significant risk of oral cancer was also evident for individual polymorphisms of cyclin E (rs1406), cyclin H (rs3093816), cyclin D1-1 (rs647451), cyclin D2 (rs3217901) and Rb1-2 (rs3092904). The risk of oral cancer increased significantly as the number of unfavourable genotypes in the pathway increased, and so the results point to a stronger combined effect of polymorphisms in important cell cycle regulatory genes on predisposition to oral cancer. PMID:24947332

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

    PubMed Central

    Gao, Bo; Russell, Amanda; Beesley, Jonathan; Chen, Xiao Qing; Healey, Sue; Henderson, Michelle; Wong, Mark; Emmanuel, Catherine; Galletta, Laura; Johnatty, Sharon E.; Bowtell, David; Bowtell, David; Chenevix-Trench, Georgia; deFazio, Anna; Gertig, Dorota; Green, Adle; Webb, Penelope; Hung, Jillian; Moore, Sue; Traficante, Nadia; Fereday, Sian; Harrap, Karen; Sadkowsky, Troy; Pandeya, Nirmala; Stuart-Harris, Robin; Kirsten, Fred; Rutovitz, Josie; Clingan, Peter; Glasgow, Amanda; Proietto, Anthony; Braye, Stephen; Otton, Greg; Shannon, Jennifer; Bonaventura, Tony; Stewart, James; Begbie, Stephen; Friedlander, Michael; Bell, David; Baron-Hay, Sally; Ferrier, Alan; Gard, Greg; Nevell, David; Pavlakis, Nick; Valmadre, Sue; Young, Barbara; Camaris, Catherine; Crouch, Roger; Edwards, Lyndal; Hacker, Neville; Marsden, Donald; Robertson, Greg; Beale, Phillip; Beith, Jane; Carter, Jonothan; Dalrymple, Chris; Hamilton, Anne; Houghton, Roger; Russell, Peter; Links, Matthew; Grygiel, John; Hill, Jane; Brand, Alison; Byth, Karen; Jaworski, Richard; Harnett, Paul; Sharma, Raghwa; Achen, Anita; Wain, Gerard; Ward, Bruce; Papadimos, David; Crandon, Alex; Cummings, Margaret; Horwood, Ken; Obermair, Andreas; Perrin, Lew; Wyld, David; Nicklin, Jim; Davy, Margaret; Oehler, Martin K; Hall, Chris; Dodd, Tom; Healy, Tabitha; Pittman, Ken; Henderson, Doug; Miller, John; Pierdes, John; Blomfield, Penny; Challis, David; McIntosh, Robert; Parker, Andrew; Brown, Bob; Rome, Robert; Allen, David; Grant, Peter; Hyde, Simon; Laurie, Rohan; Robbie, Melissa; Healy, David; Jobling, Tom; Manolitsas, Tom; McNealage, Jane; Rogers, Peter; Susil, Beatrice; Sumithran, Eric; Simpson, Ian; Phillips, Kelly; Rischin, Danny; Fox, Stephen; Johnson, Daryl; Waring, Paul; Lade, Stephen; Loughrey, Maurice; O’Callaghan, Neil; Murray, William; Billson, Virginia; Pyman, Jan; Neesham, Debra; Quinn, Michael; Underhill, Craig; Bell, Richard; Ng, Leong-Fook; Blum, Robert; Ganju, Vinod; Hammond, Ian; Leung, Yee; McCartney, Anthony; Buck, Martin; Haviv, Izak; Purdie, David; Whiteman, David; Zeps, Nikolajs; Malt, Mary-Rose; Mellon, Anne; Robertson, Randall; Bergh, Trish Vanden; Jones, Marian; Mackenzie, Patricia; Maidens, Jane; Nattress, Kath; Chiew, Yoke-Eng; Stenlake, Annie; Sullivan, Helen; Alexander, Barbara; Ashover, Pat; Brown, Sue; Corrish, Tracy; Green, Lyn; Jackman, Leah; Ferguson, Kaltin; Martin, Karen; Martyn, Adam; Ranieri, Barbara; White, Jo; Jayde, Victoria; Bowes, Leanne; Mamers, Pamela; Galletta, Laura; Giles, Debra; Hendley, Joy; Alsop, Katherine; Schmidt, Trudy; Shirley, Helen; Ball, Colleen; Young, Cherry; Viduka, Suzanna; Tran, Hoa; Bilic, Sanela; Glavinas, Lydia; Brooks, Julia; Haber, Michelle; Norris, Murray; Harnett, Paul; Chenevix-Trench, Georgia; Balleine, Rosemary L.; deFazio, Anna

    2014-01-01

    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. PMID:24810093

  18. [Single-cell detection of EGFR gene mutation in circulating tumor cells in lung cancer].

    PubMed

    Shuai, Sun; Yuliang, Deng

    2015-12-01

    Circulating tumor cells (CTCs) are cells that shed from a primary tumor and enter the peripheral blood circulation. The CTCs are closely associated with tumor development and metastasis because of its high heterogeneity. However, there are still no effective methods to detect single-cell heterogeneity of the CTCs. To this end, we developed a method to detect gene mutation in CTCs at the single-cell level and applied it to the detection of EGFR gene mutation in single lung cancer CTC. Specifically, the rare CTCs were captured from blood using an integrated microfluidic system, and then were released into a microchip with thousands of nanoliter wells to isolate single CTC. The single CTC was then transferred into a PCR tube under the microscope for single-cell genome amplification and detection of EGFR gene mutation. We firstly modified chip and capillary and optimized PCR conditions (annealing temperature, number of cycles) using non-small-cell lung cancer (NSCLC) cell lines A549, NCI-H1650 and NCI-H1975 as samples, which showed maximal amplification after 30 cycles with an annealing temperature at 59℃. We then successfully detected blood samples from NSCLC patients using this method. 5 CTCs were obtained from 2 mL patient's blood and the sequencing of EGFR exons 18, 19, 20 and 21 showed no mutations. Our results demonstrated that this method is sensitive enough to detect gene mutation in single CTC and has guiding significance in clinic research. PMID:26704950

  19. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

    PubMed Central

    Wilkins, Anna; Mossop, Helen; Syndikus, Isabel; Khoo, Vincent; Bloomfield, David; Parker, Chris; Logue, John; Scrase, Christopher; Patterson, Helen; Birtle, Alison; Staffurth, John; Malik, Zafar; Panades, Miguel; Eswar, Chinnamani; Graham, John; Russell, Martin; Kirkbride, Peter; O'Sullivan, Joe M; Gao, Annie; Cruickshank, Clare; Griffin, Clare; Dearnaley, David; Hall, Emma

    2015-01-01

    Summary Background Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. Methods The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b–T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry

  20. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS):a randomised, multicentre, open-label, phase 3 non-inferiority trial

    PubMed Central

    Donker, Mila; van Tienhoven, Geertjan; Straver, Marieke E; Meijnen, Philip; van de Velde, Cornelis J H; Mansel, Robert E; Cataliotti, Luigi; Westenberg, A Helen; Klinkenbijl, Jean H G; Orzalesi, Lorenzo; Bouma, Willem H; van der Mijle, Huub C J; Nieuwenhuijzen, Grard A P; Veltkamp, Sanne C; Slaets, Leen; Duez, Nicole J; de Graaf, Peter W; van Dalen, Thijs; Marinelli, Andreas; Rijna, Herman; Snoj, Marko; Bundred, Nigel J; Merkus, Jos W S; Belkacemi, Yazid; Petignat, Patrick; Schinagl, Dominic A X; Coens, Corneel; Messina, Carlo G M; Bogaerts, Jan; Rutgers, Emiel J T

    2014-01-01

    Summary Background If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods Patients with T1–2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1–8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary

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

    PubMed Central

    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. PMID:26301412

  2. 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.

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

    PubMed

    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.

  4. High-Resolution CT Imaging of Single Breast Cancer Microcalcifications In Vivo

    PubMed Central

    Inoue, Kazumasa; Liu, Fangbing; Hoppin, Jack; Lunsford, Elaine P.; Lackas, Christian; Hesterman, Jacob; Lenkinski, Robert E.; Fujii, Hirofumi; Frangioni, John V.

    2010-01-01

    Microcalcification is a hallmark of breast cancer and a key diagnostic feature for mammography. We recently described the first robust animal model of breast cancer microcalcification. In this study, we hypothesized that high-resolution computed tomography (CT) could potentially detect the genesis of a single microcalcification in vivo and quantify its growth over time. Using a commercial CT scanner, we systematically optimized acquisition and reconstruction parameters. Two ray-tracing image reconstruction algorithms were tested, a voxel-driven “fast” cone beam algorithm (FCBA) and a detector-driven “exact” cone beam algorithm (ECBA). By optimizing acquisition and reconstruction parameters, we were able to achieve a resolution of 104 µm full-width at half maximum (FWHM). At an optimal detector sampling frequency, ECBA provided a 28 µm (21%) FWHM improvement in resolution over FCBA. In vitro, we were able to image a single 300 µm by 100 µm hydroxyapatite crystal. In a syngeneic rat model of breast cancer, we were able to detect the genesis of a single microcalcification in vivo and follow its growth longitudinally over weeks. Taken together, this study provides an in vivo “gold standard” for the development of calcification-specific contrast agents and a model system for studying the mechanism of breast cancer microcalcification. PMID:21504703

  5. 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.

  6. 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

  7. Distinctions between dynamic characteristics of the single EG5 motor protein along neural vs. cancerous microtubules.

    PubMed

    Feizabadi, Mitra Shojania; Jun, Yonggun; Reddy, J N Babu

    2016-09-30

    The kinesin 5 motor contributes critically to mitosis, and is often upregulated in cancer. In vitro motility studies of kinesin 5 moving along bovine brain microtubules indicate that the motors have limited processivity. Cancer cells have abnormal mitotic behavior, so one might wonder whether the functional properties of kinesin 5 change in such a background. Because there could be multiple unknown changes in cancerous vs normal cells, we chose to address this question in a controlled in vitro environment. Specifically, through a series of parallel experiments along bovine brain vs. breast cancer microtubules, we quantified the in vitro motility characteristics of single Eg5 molecular motors along these two types of microtubules, combining the utilization of an optical trapping technique with a study of motion in the unloaded regime. The obtained values indicate that Eg5 processivity is 40% less along MCF7 microtubules, compared to that measured on bovine brain MTs. Interestingly, not all single-molecule properties are altered, as the velocity of the single motor doesn't show any significant changes on either track, though the binding time along MCF7 microtubules is almost 25% shorter. The current results, in conjunction with our previously reported outcomes of the evaluation of the Eg5's characteristics under external load, show that in transition from no-load to high-load regime, the Eg5 binding time has less sensitivity on MCF7 as compared to bovine brain MTs. This finding is intriguing, as it suggests that, potentially, groups of Eg5 motors function more effectively in the cancer background of a large ensemble, possibly contributing to faster mitosis in cancer cells.

  8. Distinctions between dynamic characteristics of the single EG5 motor protein along neural vs. cancerous microtubules.

    PubMed

    Feizabadi, Mitra Shojania; Jun, Yonggun; Reddy, J N Babu

    2016-09-30

    The kinesin 5 motor contributes critically to mitosis, and is often upregulated in cancer. In vitro motility studies of kinesin 5 moving along bovine brain microtubules indicate that the motors have limited processivity. Cancer cells have abnormal mitotic behavior, so one might wonder whether the functional properties of kinesin 5 change in such a background. Because there could be multiple unknown changes in cancerous vs normal cells, we chose to address this question in a controlled in vitro environment. Specifically, through a series of parallel experiments along bovine brain vs. breast cancer microtubules, we quantified the in vitro motility characteristics of single Eg5 molecular motors along these two types of microtubules, combining the utilization of an optical trapping technique with a study of motion in the unloaded regime. The obtained values indicate that Eg5 processivity is 40% less along MCF7 microtubules, compared to that measured on bovine brain MTs. Interestingly, not all single-molecule properties are altered, as the velocity of the single motor doesn't show any significant changes on either track, though the binding time along MCF7 microtubules is almost 25% shorter. The current results, in conjunction with our previously reported outcomes of the evaluation of the Eg5's characteristics under external load, show that in transition from no-load to high-load regime, the Eg5 binding time has less sensitivity on MCF7 as compared to bovine brain MTs. This finding is intriguing, as it suggests that, potentially, groups of Eg5 motors function more effectively in the cancer background of a large ensemble, possibly contributing to faster mitosis in cancer cells. PMID:27590585

  9. A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat

    PubMed Central

    2011-01-01

    Background Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. Methods In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. Results Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in

  10. 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

  11. 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.

  12. Single-port versus multi-port laparoscopic surgery for colon cancer in elderly patients

    PubMed Central

    Tokuoka, Masayoshi; Ide, Yoshihito; Takeda, Mitsunobu; Hirose, Hajime; Hashimoto, Yasuji; Matsuyama, Jin; Yokoyama, Shigekazu; Fukushima, Yukio; Sasaki, Yo

    2016-01-01

    The safety of single-incision laparoscopic surgery (SLS) in elderly patients with colorectal cancer has not been established. The aim of the current study was to compare the outcomes of SLS and multi-port laparoscopic surgery (MLS) and to assess the feasibility of SLS in colorectal cancer patients aged ≥70 years. A retrospective case-control study of colon cancer patients undergoing elective surgical intervention between 2011 and 2014 was conducted. A total of 129 patients with colon cancer underwent surgery and were included in the analysis. Data regarding patient demographics, surgical variables, oncological outcomes and short-term outcomes were evaluated for statistical significance to compare MLS (n=79) and SLS (n=50) in colon cancer patients. No significant differences were observed in patient characteristics. No case required re-admission within 30 days post surgery. The mean surgery times were similar for the MLS and SLS groups when cases with left and right hemicolectomies were combined (207.7 and 215.9 min, respectively; P=0.47). In addition, overall perioperative outcomes, including blood loss, number of lymph nodes harvested, size of the surgical margin and complications, were similar between these groups. Thus, we suggest that SLS can be performed safely in elderly patients with colon cancer. PMID:27446454

  13. Predictive criteria of insignificant prostate cancer: what is the correspondence of linear extent to percentage of cancer in a single core?

    PubMed Central

    Billis, Athanase; Quintal, Maisa M.Q; Freitas, Leandro L.L; Costa, Larissa B. E.; Ferreira, Ubirajara

    2015-01-01

    Objective The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein’s criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein’s criterion “no single core with >50% cancer” has no correspondence in linear extent. The aim of this study is to find a possible correspondence. Materials and Methods From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein’s criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. Results Comparing the clinicopathologic findings with Epstein’s criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. Conclusion To pathologists that use Epstein’s criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that “no single core with >50% cancer” may correspond to >2.5 mm in linear extent. PMID:26005981

  14. 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

  15. 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

  16. Tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel.

    PubMed

    Vaidya, Gaurang Nandkishor; Acevedo, Russell

    2015-02-01

    Tumor lysis syndrome (TLS) is an oncologic emergency characterized by spillage of intracellular material into the blood caused by disruption of massive load of tumor cells. It is more commonly reported in hematological cancers and can have fatal consequences due to renal and multi-organ failure and arrhythmias due to electrolyte imbalance. We describe a case with metastatic breast cancer who presented with TLS after a single dose of paclitaxel, second such case in literature. The development of a risk stratification score to assess the need for hospitalization or close observation of these patients and the documentation of appropriate preventive strategies could help prevent such fatal occurrences. TLS should be included in the differential when cancer patients on treatment present with acute decompensation. PMID:25178848

  17. Tunable SERS-Tags-Hidden Gold Nanorattles for Theranosis of Cancer Cells with Single Laser Beam

    NASA Astrophysics Data System (ADS)

    Chen, Zhaolong; Yu, Dexin; Huang, Yu; Zhang, Zhengjun; Liu, Ting; Zhan, Jinhua

    2014-10-01

    With the use of gold nanostructures, photothermal therapy (PTT) of cancer has great advantages compared to conventional methods, such as noninvasive targeted destruction and easily operation. Generally speaking, respective diagnosis and therapy of tumor require at least two instruments, leading to incongruence of tumor borders between diagnosis and therapy. To tackle this problem, tunable SERS-tags-hidden gold nanorattles (STHGNRs) have been designed and developed here for theranosis of cancer with single laser beam. The surface plasma resonance peak of STHGNRs can be tuned from visible region to near-infrared region by controlling the cavity size and shell thickness. The outer shells not only improve the stability of the SERS reporters but also enhance the brightness by more than two order magnitude compared to gold nanoparticles. In vitro study, immuno STHGNRs can serve as theranosis agents simultaneously for sensitive and efficient theranosis of cancer cells.

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

    PubMed Central

    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; 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

    2016-01-01

    Human cancers, including breast cancers, are comprised of clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution1,2, underpinning important emergent features such as drug resistance and metastasis3–7. 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 tumours8–10. However the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours has not been systematically examined at single cell resolution. Here we show by both 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 utilizing patient-derived breast cancer xenoengraftment. PMID:25470049

  19. A single-molecule force spectroscopy study of the interactions between lectins and carbohydrates on cancer and normal cells

    NASA Astrophysics Data System (ADS)

    Zhao, Weidong; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

    2013-03-01

    The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells.The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c3nr00553d

  20. Single-Step Nanoplasmonic VEGF165 Aptasensor for Early Cancer Diagnosis

    PubMed Central

    Cho, Hansang; Yeh, Erh-Chia; Sinha, Raghu; Laurence, Ted A.; Bearinger, Jane P.; Lee, Luke P.

    2012-01-01

    Early cancer diagnosis is very important for prevention or mitigation of metastasis. However, we must improve the diagnosis and assessment of cancer by an effective and efficient method. Here, we report a single-step detection method using nanoplasmonic aptamer sensor (aptasensor), targeting a vascular endothelial growth factor-165 (VEGF165), a predominant biomarker of cancer angiogenesis. Our single-step detection is accomplished by: (1) specific target recognition by an aptamer-target molecule interaction; (2) direct readouts of the target recognition. The readout is achieved by inactivation of surface plasmon enhancement of fluorescent probes preattached to the aptamers. Our aptasensor provides the appropriate sensitivity for clinical diagnostics with a wide range of linear detection from 25 pg/mL to 25 µg/mL (= from 1.25 pM to1.25 µM), high specificity for VEGF165 against PDGF-BB, osteopontin (OPN), VEGF121, and NaCl, and temporal/thermal/biological stability. In experiments with 100 % serum and saliva from clinical samples, readouts of the aptasensor and an ELISA for VEGF165 show good agreement within the limit of the ELISA kit. We envision that our developed aptasensor holds utility for point-of-care cancer prognostics by incorporating simplicity in detection, low-cost for test, and required small sample volume. PMID:22880609

  1. Single-step nanoplasmonic VEGF165 aptasensor for early cancer diagnosis.

    PubMed

    Cho, Hansang; Yeh, Erh-Chia; Sinha, Raghu; Laurence, Ted A; Bearinger, Jane P; Lee, Luke P

    2012-09-25

    Early cancer diagnosis is very important for the prevention or mitigation of metastasis. However, effective and efficient methods are needed to improve the diagnosis and assessment of cancer. Here, we report a single-step detection method using a nanoplasmonic aptamer sensor (aptasensor), targeting a vascular endothelial growth factor-165 (VEGF(165)), a predominant biomarker of cancer angiogenesis. Our single-step detection is accomplished by (1) specific target recognition by an aptamer-target molecule interaction and (2) direct readouts of the target recognition. The readout is achieved by inactivation of surface plasmon enhancement of fluorescent probes preattached to the aptamers. Our aptasensor provides the appropriate sensitivity for clinical diagnostics with a wide range of linear detection from 25 pg/mL to 25 μg/mL (=from 1.25 pM to 1.25 μM), high specificity for VEGF(165) against PDGF-BB, osteopontin (OPN), VEGF(121), NaCl, and temporal/thermal/biological stability. In experiments with 100% serum and saliva from clinical samples, readouts of the aptasensor and an ELISA for VEGF(165) show good agreement within the limit of the ELISA kit. We envision that our developed aptasensor holds utilities for point-of-care cancer prognostics by incorporating simplicity in detection, low-cost for test, and required small sample volumes. PMID:22880609

  2. 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.

  3. 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.

  4. 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

  5. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial

    PubMed Central

    Fitzgerald, Kevin; Frank-Kamenetsky, Maria; Shulga-Morskaya, Svetlana; Liebow, Abigail; Bettencourt, Brian R; Sutherland, Jessica E; Hutabarat, Renta M; Clausen, Valerie A; Karsten, Verena; Cehelsky, Jeffrey; Nochur, Saraswathy V; Kotelianski, Victor; Horton, Jay; Mant, Timothy; Chiesa, Joseph; Ritter, James; Munisamy, Malathy; Vaishnaw, Akshay K; Gollob, Jared A; Simon, Amy

    2015-01-01

    Summary Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. Methods We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Findings Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from

  6. Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics.

    PubMed

    Manikandan, Mayakannan; Munirajan, Arasambattu Kannan

    2014-02-01

    Cancer, a complex genetic disease involving uncontrolled cell proliferation, is caused by inactivation of tumor suppressor genes and activation of oncogenes. A vast majority of these cancer causing genes are known targets of microRNAs (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA interaction and can significantly affect gene expression. We hypothesized that 3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post-transcriptional regulation, resulting in overexpression of oncogenic proteins, tumor initiation, progression, and modulation of drug response in cancer patients. Therefore, we developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further, 8 SNPs amidst them had the potential to determine therapeutic outcome in cancer patients. Functional annotation suggested that altogether these SNPs occur in proto-oncogenes enriched for kinase activities. We provide detailed in silico evidence for the functional effect of these candidate SNPs in various types of cancer.

  7. Association of single nucleotide polymorphism rs6983267 with the risk of prostate cancer

    PubMed Central

    Yang, Yuan; Wang, Wenjing; Zhang, Liangcai; Zhang, Shihua; Liu, Guiyou; Yu, Yingcui; Liao, Mingzhi

    2016-01-01

    Many studies have investigated the association between single nucleotide polymorphism (SNP) rs6983267 and the risk of prostate cancer. However, results of these studies are inconsistent. Therefore, we summarised available data and performed a meta-analysis to determine this association. Relevant articles were identified by searching the PubMed, Web of Science and Embase database. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects model. We used dominant model (GG + TG vs TT), recessive model (GG vs TG + TT) and additive model (GG +TT vs TG) to determine the association between the rs6983267 polymorphism and risk of prostate cancer. Summary, 9 studies involving 8726 participants were included in this meta-analysis. Overall, though no association was observed between the rs6983267 polymorphism and risk of prostate cancer, subgroup analysis according to ethnicity showed a significant association between the rs6983267 polymorphism and risk of prostate cancer among white European men [recessive model: GG vs TG + TT, OR=1.21, (95% CI: 1.03, 1.42), P=0.02]. Our results indicate that the GG genotype of the rs6983267 polymorphism will increase individual susceptibility to prostate cancer in white European men. PMID:27009866

  8. Association of single nucleotide polymorphism rs6983267 with the risk of prostate cancer.

    PubMed

    Yang, Yuan; Wang, Wenjing; Zhang, Liangcai; Zhang, Shihua; Liu, Guiyou; Yu, Yingcui; Liao, Mingzhi

    2016-05-01

    Many studies have investigated the association between single nucleotide polymorphism (SNP) rs6983267 and the risk of prostate cancer. However, results of these studies are inconsistent. Therefore, we summarised available data and performed a meta-analysis to determine this association. Relevant articles were identified by searching the PubMed, Web of Science and Embase database. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects model. We used dominant model (GG + TG vs TT), recessive model (GG vs TG + TT) and additive model (GG +TT vs TG) to determine the association between the rs6983267 polymorphism and risk of prostate cancer. Summary, 9 studies involving 8726 participants were included in this meta-analysis. Overall, though no association was observed between the rs6983267 polymorphism and risk of prostate cancer, subgroup analysis according to ethnicity showed a significant association between the rs6983267 polymorphism and risk of prostate cancer among white European men [recessive model: GG vs TG + TT, OR=1.21, (95% CI: 1.03, 1.42), P=0.02]. Our results indicate that the GG genotype of the rs6983267 polymorphism will increase individual susceptibility to prostate cancer in white European men.

  9. A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer

    PubMed Central

    Song, Fengju; Liu, Qun; Dai, Hongji; Zheng, Hong; Cui, Ping; Zhang, Lina; Zhang, Wei; Chen, Kexin

    2016-01-01

    A single-nucleotide polymorphism (SNP) locus rs16917496 (T > C) within the 3′-untranslated region (3′-UTR) of SET8 was associated with susceptibility in several malignancies including breast cancer. To further elucidate the prognostic relevance of this SNP in breast cancer, we conducted a clinical study as well as SET8 expression analysis in a cohort of 1,190 breast cancer patients. We demonstrated the expression levels of SET8 in TT genotype were higher than in CC genotypes, and high levels of SET8 were associated with poor survival. SET8 expression was significantly higher in breast tumor tissue than in paired adjacent normal tissue. In addition, survival analysis in 315 patients showed SNP rs16917496 was an independent prognostic factor of breast cancer outcome with TT genotype associated with poor survival compared with CC/CT genotypes. Thus, this SNP may serve as a genetic prognostic factor and a treatment target for breast cancer. Future studies are warranted. PMID:27144429

  10. Analysis of the association of HOTAIR single nucleotide polymorphism (rs920778) and risk of cervical cancer.

    PubMed

    Qiu, Haifeng; Liu, Qiuli; Li, Juan; Wang, Xiujuan; Wang, Yuan; Yuan, Zhongfu; Li, Jing; Pei, Dong-Sheng

    2016-07-01

    We recently demonstrated that overexpression of HOTAIR (Hox transcript antisense intergenic RNA) was associated with tumor progression and radio-resistance in human cervical cancer. Considering the single nucleotide polymorphism (SNP) rs920778 (C>T) could influence HOTAIR expression and cancer predisposition in other malignancies, we herein investigated the association between rs920778 status and cervical cancer susceptibility in a Chinese population. Using the specific TaqMan PCR assay, we genotyped rs920778 in 215 cervical cancer patients and 430 age-matched healthy controls. As shown in our data, TT genotype of rs920778 was significantly correlated with the upregulation of HOTAIR (p = 0.008). Compared with the healthy control, TT genotype and T allele notably indicated a much higher risk of cervical cancer [TT genotype: odds ratio (OR) = 2.186, 95% confidence interval (CI) = 1.378-3.466, p = 0.003; T allele: OR = 1.556, 95% CI = 1.221-1.981]. In addition, we also found that the TT genotype of rs920778 was correlated with advanced tumor stage (p = 0.039), highly histological grade (p = 0.013), lympho node metastasis (p < 0.001) and positive infection of high risk HPV (p < 0.001). Among the patients who underwent concurrent chemo-radiotherapy, TT genotype carriers present notably resistance to the combination of EBRT + ICBT + cisplatin (p = 0.023). In conclusion, we firstly reported that TT genotype of HOTAIR rs920778 was significantly associated with the cervical cancer susceptibility. Moreover, the TT genotype of rs920778 might be a potent prognostic marker in cervical cancer patients.

  11. Single-nucleotide polymorphisms in PSCA and the risk of breast cancer in a Chinese population

    PubMed Central

    Wang, Meng; Wang, Xijing; Fu, Sidney W.; Liu, Xinghan; Jin, Tianbo; Kang, Huafeng; Ma, Xiaobin; Lin, Shuai; Guan, Haitao; Zhang, Shuqun; Liu, Kang; Dai, Cong; Zhu, Yuyao; Dai, Zhijun

    2016-01-01

    This study explored the associations between common PSCA single-nucleotide polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560 breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was significantly associated with a high risk of breast cancer (homozygote model, odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06–2.59; recessive, OR: 1.64, 95% CI: 1.06–2.53). And stratification by menopausal status revealed an association of the minor allele of rs2294008 with breast cancer risk among premenopausal (homozygote model, OR: 2.41, 95% CI: 1.03–5.66; recessive, OR: 2.80, 95 % CI: 1.21–6.47) and postmenopausal women (allele model, OR: 1.29, 95% CI: 1.01–1.65). Rs2978974 influenced the breast cancer risk among postmenopausal women in heterozygote model (OR: 1.47, 95% CI: 1.05–2.07). When stratified by clinicopathologic features, the T allele of rs2294008 was associated with progesterone receptor status (homozygote model, OR: 1.98, 95% CI: 1.08–3.63; recessive, OR: 1.87, 95% CI: 1.04–3.37), and the rs2976392 polymorphism was associated with high lymph node metastasis risk in homozygote model (OR: 2.09, 95%CI: 1.01–4.31). Further haplotype analysis suggested that Trs2294008 Ars2976392 Grs2978974 haplotype enhances breast cancer risk (OR:1.52, 95%CI:1.23-1.89, P<0.001). Therefore, among Chinese Han women, the PSCA rs2294008, rs2978974, and rs2976392 minor alleles are associated with increased breast cancer risk especially in progesterone receptor positive breast cancer patients, with breast cancer risk in postmenopausal women, and with high lymph node metastasis risk, respectively. Moreover, Trs2294008 Ars2976392 Grs2978974 haplotype was associated with significantly increased risk of breast cancer. PMID:27050280

  12. Parallel single cancer cell whole genome amplification using button-valve assisted mixing in nanoliter chambers.

    PubMed

    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.

  13. 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

  14. Parallel single cancer cell whole genome amplification using button-valve assisted mixing in nanoliter chambers.

    PubMed

    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

  15. A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel/prednisone in patients with castration-resistant prostate cancer.

    PubMed

    Wiechno, Paweł; Somer, Bradley G; Mellado, Begoña; Chłosta, Piotr L; Cervera Grau, José Manuel; Castellano, Daniel; Reuter, Christoph; Stöckle, Michael; Kamradt, Jörn; Pikiel, Joanna; Durán, Ignacio; Wedel, Steffen; Callies, Sophie; André, Valérie; Hurt, Karla; Brown, Jacqueline; Lahn, Michael; Heinrich, Bernhard

    2014-03-01

    Castration-resistant prostate cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups. PMID:24246407

  16. 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

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

    PubMed

    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 Central

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

    2016-01-01

    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. PMID:27677461

  19. Diagnosis of pelvic lymph node metastasis in prostate cancer using single optical fiber probe.

    PubMed

    Denkçeken, Tuba; Canpolat, Murat; Baykara, Mehmet; Başsorgun, İbrahim; Aktaş-Samur, Anıl

    2016-09-01

    Elastic light single-scattering spectroscopy system (ELSSS) is a biomedical tool which is used for detection of cancerous tissues ex-vivo. ELSSS spectra depend primarily on the size of scatterers in the tissue and are not directly related to changes in the absorption which are caused by variations of the biological macromolecules. In the present study, we aimed to detect metastasis in the pelvic lymph node by using combination of Principal Components Analysis (PCA) and Linear Discriminant Analysis (LDA). Single-scattering spectra in the 450-750nm wavelength regions were obtained from the total of 83 reactive lymph node and 12 metastatic lymph node samples from 10 prostatic cancer patients. The ELSSS spectral data were compared against the "gold standard" histopathology results. Data analyses were done via using PCA, followed by LDA. Receiver Operating Characteristic (ROC) curve analysis was employed for differentiating performance. The classification based on discriminant score provided sensitivity of 100% and specificity of 96.4%, in differentiating non-metastatic (reactive) from metastatic pelvic lymph nodes, with a Positive Predictive Value (PPV) of 0.8, a Negative Predictive Value (NPV) of 0.99 and the area under the ROC curve (AUC) of 0.99, respectively. In this study, it was shown that ELSSS system can accurately distinguish reactive and metastatic pelvic lymph nodes of prostate cancer with high PPV and NPV. It can be concluded that diagnostic accuracy of ELSSS system allows detecting metastatic tissues during operation.

  20. 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.

  1. 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

  2. In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Khlebtsov, Nicolai G.; Tuchin, Valery V.

    2006-12-01

    A new photoacoustic flow cytometry was developed for real-time detection of circulating cells, nanoparticles, and contrast agents in vivo. Its capability, integrated with photothermal and optical clearing methods, was demonstrated using a near-infrared tunable laser to characterize the in vivo kinetics of Indocyanine Green alone and single cancer cells labeled with gold nanorods and Indocyanine Green in the vasculature of the mouse ear. In vivo applications are discussed, including selective nanophotothermolysis of metastatic squamous cells, label-free detection of melanoma cells, study of pharmokinetics, and immune response to apoptotic and necrotic cells, with potential translation to humans. The threshold sensitivity is estimated as one cancer cell in the background of 107 normal blood cells.

  3. 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.

  4. Cervical cancer screening: Safety, acceptability, and feasibility of a single-visit approach in Bulawayo, Zimbabwe

    PubMed Central

    Fallala, Muriel S.

    2015-01-01

    Background Cervical cancer is the commonest cancer amongst African women, and yet preventative services are often inadequate. Aim The purpose of the study was to assess the safety, acceptability and feasibility of visual inspection with acetic acid and cervicography (VIAC) followed by cryotherapy or a loop electrical excision procedure (LEEP) at a single visit for prevention of cancer of the cervix. Setting The United Bulawayo Hospital, Zimbabwe. Methods The study was descriptive, using retrospective data extracted from electronic medical records of women attending the VIAC clinic. Over 24 months 4641 women visited the clinic and were screened for cervical cancer using VIAC. Cryotherapy or LEEP was offered immediately to those that screened positive. Treated women were followed up at three months and one year. Results The rate of positive results on VIAC testing was 10.8%. Of those who were eligible, 17.0% received immediate cryotherapy, 44.1% received immediate LEEP, 1.9% delayed treatment, and 37.0% were referred to a gynaecologist. No major complications were recorded after cryotherapy or LEEP. Amongst those treated 99.5% expressed satisfaction with their experience. Only 3.2% of those treated at the clinic had a positive result on VIAC one year later. The service was shown to be feasible to sustain over time with the necessary consumables. There were no service-related treatment postponements and the clinic staff and facility were able to meet the demand for the service. Conclusion A single-visit approach using VIAC, followed by cryotherapy or LEEP, proved to be safe, acceptable and feasible in an urban African setting in Bulawayo, Zimbabwe. Outcomes a year later suggested that treatment had been effective. PMID:26245601

  5. 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

  6. Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study

    PubMed Central

    Bonnefoi, H.; Jacot, W.; Saghatchian, M.; Moldovan, C.; Venat-Bouvet, L.; Zaman, K.; Matos, E.; Petit, T.; Bodmer, A.; Quenel-Tueux, N.; Chakiba, C.; Vuylsteke, P.; Jerusalem, G.; Brain, E.; Tredan, O.; Messina, C. G. M.; Slaets, L.; Cameron, D.

    2015-01-01

    Background Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. Patients and methods Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. Results From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3–4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. Conclusions This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce

  7. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial

    PubMed Central

    Herbst, Roy S; Sun, Yan; Eberhardt, Wilfried E E; Germonpré, Paul; Saijo, Nagahiro; Zhou, Caicun; Wang, Jie; Li, Longyun; Kabbinavar, Fairooz; Ichinose, Yukito; Qin, Shukui; Zhang, Li; Biesma, Bonne; Heymach, John V; Langmuir, Peter; Kennedy, Sarah J; Tada, Hiroomi; Johnson, Bruce E

    2011-01-01

    Summary Background Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC). Methods Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB–IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 IV every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov, number NCT00312377. Findings 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus docetaxel alone (hazard ratio [HR] 0·79, 97·58% CI 0·70–0·90; p<0·0001); median PFS was 4·0 months in the vandetanib group versus 3·2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0·79, 0·62–1·00, p=0·024); median PFS was 4·6 months in the vandetanib group versus 4·2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel

  8. 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

  9. Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study.

    PubMed

    Wheler, Jennifer J; Janku, Filip; Naing, Aung; Li, Yali; Stephen, Bettzy; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Karp, Daniel; Falchook, Gerald S; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Anderson, Roosevelt; Ke, Danxia; Miller, Vincent; Yelensky, Roman; Lee, J Jack; Hong, David S; Kurzrock, Razelle

    2016-07-01

    Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly targeted drugs. We report the findings of a prospective, single-center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N = 122/188, 65%) or unmatched therapy (N = 66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1-14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease ≥6 months/partial/complete remission [22% (high scores) vs. 9% (low scores), P = 0.024], longer time-to-treatment failure [hazard ratio (HR) = 0.52; 95% confidence interval (CI) = 0.36-0.74; P = 0.0003], and survival (HR = 0.65; 95% CI = 0.43-1.0; P = 0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented. Cancer Res; 76(13); 3690-701. ©2016 AACR. PMID:27197177

  10. 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

  11. Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk.

    PubMed

    Rogler, Anja; Hoja, Sabine; Socher, Eileen; Nolte, Elke; Wach, Sven; Wieland, Wolf; Hofstädter, Ferdinand; Goebell, Peter J; Wullich, Bernd; Hartmann, Arndt; Stoehr, Robert

    2013-01-01

    In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1 mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242. PMID:24133576

  12. Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk

    PubMed Central

    Rogler, Anja; Hoja, Sabine; Socher, Eileen; Nolte, Elke; Wach, Sven; Wieland, Wolf; Hofstädter, Ferdinand; Goebell, Peter J; Wullich, Bernd; Hartmann, Arndt; Stoehr, Robert

    2013-01-01

    In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1 mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242. PMID:24133576

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

    PubMed Central

    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

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. 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 tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. 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

  14. [Biological implant in single-stage reconstruction of mammary gland for cancer].

    PubMed

    Zikiriakhodzhaev, A D; Ermoshchenkova, M V

    2015-01-01

    Brief literature review about features of biological implants application for mammary gland reconstruction is presented in the article. Possible complications after such materials use, first experience of acellular dermal matrix administration for single-stage mammary gland reconstruction in 6 patients with breast cancer are also described. We offered surgical techniques, complications and methods of its treatment. We presented advantages of biological implant use which are consisted in decrease of surgical damage and duration of surgery, opportunity for enlargement of pocket for implant, decrease of pain syndrome. PMID:25909549

  15. A single nucleotide polymorphism of the TNRC9 gene associated with breast cancer risk in Chinese Han women.

    PubMed

    Chen, F; Zhou, J; Xue, Y; Yang, S; Xiong, M; Li, Y; Liu, Q

    2014-01-01

    A single nucleotide polymorphism (SNP) in the TNRC9 gene was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry. We investigated whether TNRC9 polymorphisms are associated with risk of breast cancer in Chinese women of the Han nationality. We genotyped the SNPs rs3803662, rs1362548, rs1123428 in 870 women, including 388 breast cancer patients and 482 healthy controls, via the PCR-single strand conformation polymorphism procedure and by sequence detection. We found that the T allele and the TT genotype of the SNP rs38033662 is significantly associated with risk for breast cancer in Chinese Han women; however, no significant association was found for rs1362548 or rs1123428. We conclude that SNP rs3803662 is a putative risk factor for breast cancer in Chinese Han women.

  16. Prevalence of Precancerous Conditions and Gastric Cancer Based upon the National Cancer Screening Program in Korea for 7 Years, Single Center Experience

    PubMed Central

    Kang, Ji Hyuk; Lim, Yun Jeong; Kang, Jung Hyun; Yang, Jae Nam; Shin, Seung Min; Choi, Jae Hyeuk; Lee, Jin Ho

    2015-01-01

    Aims. Gastric cancer is the second most prevalent cancer and the third leading cause of cancer-related deaths in Korea. The National Cancer Screening Program (NCSP) has implemented esophagogastroduodenoscopy (EGD) biennially for all Koreans starting in their 40s. This study was conducted to estimate the clinical relevance of NCSP through identifying the prevalence of gastric disease, including cancer. Materials and Methods. Data from 40,821 subjects who received the screening EGD in the single center for 7 years were retrospectively investigated. Results. The overall prevalence of nonatrophic/atrophic/metaplastic gastritis, peptic ulcer, adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC) was 44.28%, 27.97%, 14.95%, 0.59%, 0.43%, 0.21%, and 0.09%, respectively. The prevalence of metaplastic gastritis, peptic ulcer, adenoma, EGC, and AGC was significantly higher in men than in women. The prevalence of preneoplastic/neoplastic disease significantly increased with age. Judged from the ratio of EGC to AGC, the proportion of EGC made up to 70% of all cancers. Conclusions. Screening endoscopy starting for people in their 40s should be strongly recommended for the elderly. Through the NCSP, the early detection of gastric cancer might contribute to the decreased mortality rate due to gastric cancer in Korea. PMID:25642244

  17. Single-cell Western blotting after whole-cell imaging to assess cancer chemotherapeutic response.

    PubMed

    Kang, Chi-Chih; Lin, Jung-Ming G; Xu, Zhuchen; Kumar, Sanjay; Herr, Amy E

    2014-10-21

    Intratumor heterogeneity remains a major obstacle to effective cancer therapy and personalized medicine. Current understanding points to differential therapeutic response among subpopulations of tumor cells as a key challenge to successful treatment. To advance our understanding of how this heterogeneity is reflected in cell-to-cell variations in chemosensitivity and expression of drug-resistance proteins, we optimize and apply a new targeted proteomics modality, single-cell western blotting (scWestern), to a human glioblastoma cell line. To acquire both phenotypic and proteomic data on the same, single glioblastoma cells, we integrate high-content imaging prior to the scWestern assays. The scWestern technique supports thousands of concurrent single-cell western blots, with each assay comprised of chemical lysis of single cells seated in microwells, protein electrophoresis from those microwells into a supporting polyacrylamide (PA) gel layer, and in-gel antibody probing. We systematically optimize chemical lysis and subsequent polyacrylamide gel electrophoresis (PAGE) of the single-cell lysate. The scWestern slides are stored for months then reprobed, thus allowing archiving and later analysis as relevant to sparingly limited, longitudinal cell specimens. Imaging and scWestern analysis of single glioblastoma cells dosed with the chemotherapeutic daunomycin showed both apoptotic (cleaved caspase 8- and annexin V-positive) and living cells. Intriguingly, living glioblastoma subpopulations show up-regulation of a multidrug resistant protein, P-glycoprotein (P-gp), suggesting an active drug efflux pump as a potential mechanism of drug resistance. Accordingly, linking of phenotype with targeted protein analysis with single-cell resolution may advance our understanding of drug response in inherently heterogeneous cell populations, such as those anticipated in tumors.

  18. Solo Intracorporeal Esophagojejunostomy Reconstruction Using a Laparoscopic Scope Holder in Single-Port Laparoscopic Total Gastrectomy for Early Gastric Cancer.

    PubMed

    Ahn, Sang-Hoon; Son, Sang-Yong; Jung, Do Hyun; Park, Young Suk; Shin, Dong Joon; Park, Do Joong; Kim, Hyung-Ho

    2015-06-01

    Single-incision laparoscopic total gastrectomy for gastric cancer has recently been reported by Seoul National University Bundang Hospital. However, this is not a popular procedure primarily because of the technical difficulties involved in achieving consistent intracorporeal esophagojejunostomy. At Seoul National University Bundang Hospital, we recently introduced a simple, easy-to-use, low-profile laparoscopic manual scope holder that enables the maintenance of a stable field of view, the most demanding condition in single-port gastrectomy. In this technical report, we describe in detail the world's first solo single-incision laparoscopic total gastrectomy with D1+ lymph node dissection and intracorporeal esophagojejunostomy for proximal early gastric cancer.

  19. 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

  20. A collagen-binding EGFR single-chain Fv antibody fragment for the targeted cancer therapy.

    PubMed

    Liang, Hui; Li, Xiaoran; Chen, Bing; Wang, Bin; Zhao, Yannan; Zhuang, Yan; Shen, He; Zhang, Zhijun; Dai, Jianwu

    2015-07-10

    Collagen, a primary component of the extracellular matrix (ECM), is highly expressed in a variety of cancers and influences the tumor microenvironment by increasing the recruitment of macrophages and endothelial cells. Therefore, collagen is a highly promising target for cancer therapy. The collagen-binding domain (CBD) can dynamically bind to collagen and achieve the sustained release of CBD-fused protein in the collagen network. Here, we developed a collagen-binding epidermal growth factor receptor (EGFR) antibody fragment for targeting the collagen-rich ECM in tumors. The single chain fragment variable (scFv) of cetuximab was fused to CBD (CBD-scFv) and expressed in Pichia pastoris. CBD-scFv preserved the antigen binding domain and anti-tumor activity of cetuximab in vitro. Moreover, CBD-scFv displayed a collagen binding ability due to the function of CBD. In vivo experiments revealed that CBD-scFv bound to collagen and achieved sustained release in tumors. Furthermore, CBD-scFv significantly suppressed the growth of tumors in A431 xenografts. Therefore, CBD-scFv had a potential therapeutic value for the collagen-rich carcinomas. The specific target and sustained release of CBD-scFv in tumors could be a new approach for targeted drug delivery in cancer therapy.

  1. Vascular targeted single-walled carbon nanotubes for near-infrared light therapy of cancer

    NASA Astrophysics Data System (ADS)

    Prickett, Whitney M.; Van Rite, Brent D.; Resasco, Daniel E.; Harrison, Roger G.

    2011-11-01

    A new approach for targeting carbon nanotubes to the tumor vasculature was tested using human endothelial cells and MCF-7 breast cancer cells in vitro. Single-walled carbon nanotubes were functionalized with the F3 peptide using a polyethylene glycol linker to target nucleolin, a protein found on the surface of endothelial cells in the vasculature of solid tumors. Confocal microscopy and Raman analysis confirmed that the conjugate was internalized by actively dividing endothelial cells. Dividing endothelial cells were used to mimic these cells in the tumor vasculature. Incubation with the conjugate for 8 h or more caused significant cell death in both actively dividing endothelial cells and MCF-7 breast cancer cells, an effect that is hypothesized to be due to the massive uptake of the conjugate. This targeted cell killing was further enhanced when coupled with near-infrared laser treatment. For confluent (non-dividing) endothelial cells, no cytotoxic effect was seen for incubation alone or incubation coupled with laser treatment. These results are promising and warrant further studies using this conjugate for cancer treatment in vivo.

  2. Single-cell states in the estrogen response of breast cancer cell lines.

    PubMed

    Casale, Francesco Paolo; Giurato, Giorgio; Nassa, Giovanni; Armond, Jonathan W; Oates, Chris J; Corá, Davide; Gamba, Andrea; Mukherjee, Sach; Weisz, Alessandro; Nicodemi, Mario

    2014-01-01

    Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. PMID:24586334

  3. Single-Cell States in the Estrogen Response of Breast Cancer Cell Lines

    PubMed Central

    Casale, Francesco Paolo; Giurato, Giorgio; Nassa, Giovanni; Armond, Jonathan W.; Oates, Chris J.; Corá, Davide; Gamba, Andrea; Mukherjee, Sach; Weisz, Alessandro; Nicodemi, Mario

    2014-01-01

    Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. PMID:24586334

  4. Proteomic Consequences of a Single Gene Mutation in a Colorectal Cancer Model

    PubMed Central

    2011-01-01

    The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signaling, occur in up to 60% of CRC tumors. Here we examine the proteomic consequences of a single gene mutation by using an isogenic CRC cell culture model in which wildtype APC expression has been ectopically restored. Using LC–MS/MS label free shotgun proteomics, over 5000 proteins were identified in SW480Null (mutant APC) and SW480APC (APC restored). We observed 155 significantly differentially expressed proteins between the two cell lines, with 26 proteins showing opposite expression trends relative to gene expression measurements. Protein changes corresponded to previously characterized features of the APCNull phenotype: loss of cell adhesion proteins, increase in cell cycle regulators, alteration in Wnt signaling related proteins, and redistribution of β-catenin. Increased expression of RNA processing and isoprenoid biosynthetic proteins occurred in SW480Null cells. Therefore, shotgun proteomics reveals proteomic differences associated with a single gene change, including many novel differences that fall outside known target pathways. PMID:22103262

  5. Multidisciplinary Service Utilization Pattern by Advanced Head and Neck Cancer Patients: A Single Institution Study

    PubMed Central

    Junn, Jacqueline C.; Kim, Irene A.; Zahurak, Marianna L.; Tan, Marietta; Fan, Katherine Y.; Lake, Spencer T.; Zaboli, David; Messing, Barbara P.; Ulmer, Karen; Harrer, Karen B.; Gold, Dorothy; Ryniak, Keri L.; Zinreich, Eva S.; Tang, Mei; Levine, Marshall A.; Blanco, Ray G.; Saunders, John R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Purpose. To analyze the patterns and associations of adjunctive service visits by head and neck cancer patients receiving primary, concurrent chemoradiation therapy. Methods. Retrospective chart review of patients receiving adjunctive support during a uniform chemoradiation regimen for stages III-IV head and neck squamous cell carcinoma. Univariate and multivariate models for each outcome were obtained from simple and multivariate linear regression analyses. Results. Fifty-two consecutive patients were assessed. Female gender, single marital status, and nonprivate insurance were factors associated with an increased number of social work visits. In a multivariate analysis, female gender and marital status were related to increased social work services. Female gender and stage IV disease were significant for increased nursing visits. In a multivariate analysis for nursing visits, living greater than 20 miles between home and hospital was a negative predictive factor. Conclusion. Treatment of advanced stage head and neck cancer with concurrent chemoradiation warrants a multidisciplinary approach. Female gender, single marital status, and stage IV disease were correlated with increased utilization of social work and nursing services. Distance over 20 miles from the center was a negative factor. This information may help guide the treatment team to allocate resources for the comprehensive care of patients. PMID:23118755

  6. 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.

  7. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial

    PubMed Central

    Buzdar, Aman U; Suman, Vera J; Meric-Bernstam, Funda; Leitch, A Marilyn; Ellis, Matthew J; Boughey, Judy C; Unzeitig, Gary; Royce, Melanie; McCall, Linda M; Ewer, Michael S; Hunt, Kelly K

    2014-01-01

    Summary Background Neoadjuvant chemotherapy with trastuzumab for patients with HER2-positive breast cancer can produce a pathological complete response in the breast in 30–65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. Methods This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2 (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m2 and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. Findings From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56.5%, 95% CI 47.8–64.9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54.2%, 95% CI 45.7–62.6) who received concurrent

  8. 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

  9. Functional and Structural Consequences of Damaging Single Nucleotide Polymorphisms in Human Prostate Cancer Predisposition Gene RNASEL.

    PubMed

    Datta, Amit; Mazumder, Md Habibul Hasan; Chowdhury, Afrin Sultana; Hasan, Md Anayet

    2015-01-01

    A commonly diagnosed cancer, prostate cancer (PrCa), is being regulated by the gene RNASEL previously known as PRCA1 codes for ribonuclease L which is an integral part of interferon regulated system that mediates antiviral and antiproliferative role of the interferons. Both somatic and germline mutations have been implicated to cause prostate cancer. With an array of available Single Nucleotide Polymorphism data on dbSNP this study is designed to sort out functional SNPs in RNASEL by implementing different authentic computational tools such as SIFT, PolyPhen, SNPs&GO, Fathmm, ConSurf, UTRScan, PDBsum, Tm-Align, I-Mutant, and Project HOPE for functional and structural assessment, solvent accessibility, molecular dynamics, and energy minimization study. Among 794 RNASEL SNP entries 124 SNPs were found nonsynonymous from which SIFT predicted 13 nsSNPs as nontolerable whereas PolyPhen-2 predicted 28. SNPs found on the 3' and 5' UTR were also assessed. By analyzing six tools having different perspectives an aggregate result was produced where nine nsSNPs were found to be most likely to exert deleterious effect. 3D models of mutated proteins were generated to determine the functional and structural effect of the mutations on ribonuclease L. The initial findings were reinforced by the results from I-Mutant and Project HOPE as these tools predicted significant structural and functional instability of the mutated proteins. Expasy-ProSit tool defined the mutations to be situated in the functional domains of the protein. Considering previous analysis this study revealed a conclusive result deducing the available SNP data on the database by identifying the most damaging three nsSNP rs151296858 (G59S), rs145415894 (A276V), and rs35896902 (R592H). As such studies involving polymorphisms of RNASEL were none to be found, the results of the current study would certainly be helpful in future prospects concerning prostate cancer in males. PMID:26236721

  10. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: a single center experience

    PubMed Central

    Choi, Euncheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results. PMID:27306776

  11. 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.

  12. Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer

    PubMed Central

    Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte

    2016-01-01

    Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134

  13. 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

  14. 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.

  15. 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

  16. Functionalization of single-walled carbon nanotubes and their binding to cancer cells

    PubMed Central

    Madani, Seyed Yazdan; Tan, Aaron; Dwek, Miriam; Seifalian, Alexander M

    2012-01-01

    Background Single-walled carbon nanotubes (SWCNTs) have novel properties including their nanoscale size and ease of cellular uptake. This makes them useful for drug delivery, and their photo-thermal effects make them potentially useful in a wide range of applications, particularly the treatment of solid tumors. The poor solubility of SWCNTs has, however, been an issue that may potentially limit the utility of SWCNTs for cancer treatment. Functionalization of the surface of the tubes may be an approach to overcome this problem. Methods SWCNTs were refluxed in HNO3/H2SO4 (1:3) at 120°C for 120 minutes. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and near infrared (NIR) light exposure were used to assess the functionalization process. The attachment of a carbohydrate-binding protein (lectin) labeled with fluorescein isothiocyanate to the functionalized SWCNTs enabled evaluation of the functionalization step via confocal microscopy. The lectin from Helix pomatia, (Helix pomatia agglutinin [HPA]), can detect changes in protein glycosylation associated with aggressive metastatic cancer. The interaction between the lectin HPA alone and HPA conjugated to the functionalized SWCNTs with human breast cancer cells (MCF-7) was measured using a quartz crystal microbalance biosensor. Results Following the functionalization process, TEM images showed a layer had formed on the surface of the SWCNTs. In the FTIR experiment, results illustrated the presence of the −COOH group on the functionalized SWCNTs. Contact angle measurements showed that upon functionalization the hydrophilicity of the SWCNTs increased. The temperature increase in the liquid (supernatant) surrounding the functionalized SWCNTs following exposure to light in the NIR (808 nm) was greater than for non-functionalized SWCNTs. The biosensor work showed that HPA binds with high affinity (nanomolar range) to human breast cancer cells; HPA

  17. Upregulation of c-MYC in cis through a Large Chromatin Loop Linked to a Cancer Risk-Associated Single-Nucleotide Polymorphism in Colorectal Cancer Cells▿

    PubMed Central

    Wright, Jason B.; Brown, Seth J.; Cole, Michael D.

    2010-01-01

    Genome-wide association studies have mapped many single-nucleotide polymorphisms (SNPs) that are linked to cancer risk, but the mechanism by which most SNPs promote cancer remains undefined. The rs6983267 SNP at 8q24 has been associated with many cancers, yet the SNP falls 335 kb from the nearest gene, c-MYC. We show that the beta-catenin-TCF4 transcription factor complex binds preferentially to the cancer risk-associated rs6983267(G) allele in colon cancer cells. We also show that the rs6983267 SNP has enhancer-related histone marks and can form a 335-kb chromatin loop to interact with the c-MYC promoter. Finally, we show that the SNP has no effect on the efficiency of chromatin looping to the c-MYC promoter but that the cancer risk-associated SNP enhances the expression of the linked c-MYC allele. Thus, cancer risk is a direct consequence of elevated c-MYC expression from increased distal enhancer activity and not from reorganization/creation of the large chromatin loop. The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops. PMID:20065031

  18. 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.

  19. Tracking surface glycans on live cancer cells with single molecule sensitivity**

    PubMed Central

    Jiang, Hao; English, Brian P.; Hazan, Rachel B.; Wu, Peng

    2015-01-01

    Using a combination of metabolically labeled glycans, bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition and controlled bleaching of fluorescent probes conjugated to azide or alkyne tagged glycans, we achieve a sufficiently low spatial density of dye labeled glycans enabling dynamic single-molecule tracking and super-resolution imaging of N-linked sialic acids and O-linked GalNAc on the membrane of live cells. Analysis of the trajectories of these dye labeled glycans in mammary cancer cells reveal constrained diffusion of both N- and O-linked glycans which we interpret as reflecting the mobility of the glycan rather than caused by transient immobilization due to spatial inhomogeneities on the plasma membrane. Stochastic optical reconstruction microscopy (STORM) imaging reveals the structure of dynamic membrane nanotubes. PMID:25515330

  20. Effect of photodynamic therapy on single cancer cells studied by integrated Raman and angular scattering microscopy

    NASA Astrophysics Data System (ADS)

    Shipp, Dustin W.; Mitra, Soumya; Foster, Thomas H.; Berger, Andrew J.

    2012-01-01

    Using integrated Raman and angular scattering microscopy (IRAM), we follow the response of EMT6 cancer cells to photodynamic therapy (PDT) treatment. The study combines two non-labelling light scattering techniques to extract chemical information and organelle sizes from single cells. Each cell is measured repeatedly over several hours to follow changes in these parameters as the cell responds to the PDT treatment. An automated algorithm identifies which parameters are changing in time. Size parameters extracted from angular scattering measurements show a decrease in the size of 1-micron-diameter scatterers in treated cells. Treated cells also exhibit trends in several Raman peaks, denoting changes in chemical concentrations of proteins, nucleic acids, and lipids. Each of these parameters - acquired from both measurement modalities - can be monitored on a cell-by-cell basis. The ability to track these chemical and structural changes over time allows access to greater knowledge of biological processes.

  1. 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.

  2. 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

    Background Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. Objectives To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. Selection criteria We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. Data collection and analysis We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi2 and I2 statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. Main results We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These

  3. Associations Between Single-Nucleotide Polymorphisms and Epidural Ropivacaine Consumption in Patients Undergoing Breast Cancer Surgery

    PubMed Central

    Liu, Jing; Jiang, Yongdong; Pang, Da; Xi, Hongjie; Liu, Yan

    2013-01-01

    Up to date, few published studies indicated the associations between genetic polymorphisms and epidural local anesthetics consumption. In this study, we investigated the associations between seven single-nucleotide polymorphisms (SNPs) and epidural ropivacaine consumption during breast cancer surgery in women from northeastern China. These seven SNPs (rs3803662 and rs12443621 in TNCR9, rs889312 in MAP3K1, rs3817198 in LSP1, rs13387042 at 2q35, rs13281615 at 8q24, and rs2046210 at 6q25.1) were identified by recent genome-wide association studies associated with tumor susceptibility. A total of 418 breast cancer women received thoracic epidural anesthesia with ropivacaine for elective mastectomy with axillary clearance. Their blood samples were genotyped for the seven SNPs using the SNaPshot method. For SNP rs13281615, the subjects with genotype AG and GG consumed a greater amount of the total epidural ropivacaine and the mean ropivacaine dose than the subjects with genotype AA (p=0.047 and p=0.003, respectively). Furthermore, no statistical differences were found in the total dose of ropivacaine, the mean consumption of ropivacaine, the onset of ropivacaine, or the initial dose of lidocaine among the three genotypic groups for the other six SNPs studied. Our study indicated that SNP rs13281615 at 8q24 was associated with the consumption of epidural ropivacaine during breast cancer surgery in northeastern Chinese women. It might provide new insights into the mechanisms of ropivacaine action and metabolism and facilitate the development of personalized medicine. PMID:23577780

  4. Binary System for MicroRNA-Targeted Imaging in Single Cells and Photothermal Cancer Therapy.

    PubMed

    Qian, Ruo-Can; Cao, Yue; Long, Yi-Tao

    2016-09-01

    Abnormal expression of microRNAs (miRNAs) is often associated with tumorigenesis, metastasis, and progression. Among them, miRNA-21 is found to be overexpressed in most of the cancer cells. Here, a binary system is designed for miRNA-21 targeted imaging and photothermal treatment in single cells. The binary system is composed by a pair of probes (probe-1 and probe-2), which are encapsulated in liposomes for cell delivery. Both of the two probes adopt gold nanoparticles (AuNPs) as the core material, and the AuNPs are functionalized with Cy5-marked molecular beacon (MB-1/MB-2 for probe-1/probe-2, respectively). The loop part of MBs are designed to be complementary with miRNA-21. Therefore, after the binary system enters into the cytoplasm, MBs can be opened upon miRNA-21 triggered hybridization, which turns "on" the fluorescence of Cy5 for the localization of miRNA-21. At the same time, a cross-linking between the probes occurs since the far ends of MB-1 and MB-2 are designed to be complementary with each other. The miRNA-induced aggregation shifts the absorption of AuNPs to near-infrared, which can be observed under dark-field microscopy (DFM) and used for the following photothermal therapy. Under near-infrared (NIR) irradiation, MCF-7 breast cancer cells are successfully killed. The proposed system can be further applied in tumor-bearing mice and shows significant therapeutic effect. This work provides a new tool for intracellular miRNA analysis and targeted treatment against cancer. PMID:27482754

  5. Binary System for MicroRNA-Targeted Imaging in Single Cells and Photothermal Cancer Therapy.

    PubMed

    Qian, Ruo-Can; Cao, Yue; Long, Yi-Tao

    2016-09-01

    Abnormal expression of microRNAs (miRNAs) is often associated with tumorigenesis, metastasis, and progression. Among them, miRNA-21 is found to be overexpressed in most of the cancer cells. Here, a binary system is designed for miRNA-21 targeted imaging and photothermal treatment in single cells. The binary system is composed by a pair of probes (probe-1 and probe-2), which are encapsulated in liposomes for cell delivery. Both of the two probes adopt gold nanoparticles (AuNPs) as the core material, and the AuNPs are functionalized with Cy5-marked molecular beacon (MB-1/MB-2 for probe-1/probe-2, respectively). The loop part of MBs are designed to be complementary with miRNA-21. Therefore, after the binary system enters into the cytoplasm, MBs can be opened upon miRNA-21 triggered hybridization, which turns "on" the fluorescence of Cy5 for the localization of miRNA-21. At the same time, a cross-linking between the probes occurs since the far ends of MB-1 and MB-2 are designed to be complementary with each other. The miRNA-induced aggregation shifts the absorption of AuNPs to near-infrared, which can be observed under dark-field microscopy (DFM) and used for the following photothermal therapy. Under near-infrared (NIR) irradiation, MCF-7 breast cancer cells are successfully killed. The proposed system can be further applied in tumor-bearing mice and shows significant therapeutic effect. This work provides a new tool for intracellular miRNA analysis and targeted treatment against cancer.

  6. 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.

  7. 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

  8. Association of single nucleotide polymorphism rs3803662 with the risk of breast cancer

    PubMed Central

    Yang, Yuan; Wang, Wenjing; Liu, Guiyou; Yu, Yingcui; Liao, Mingzhi

    2016-01-01

    Large scale association studies have identified the single nucleotide polymorphism rs3803662 associated with breast cancer risk. However, the sample size of most studies is too small. Here, we performed this meta-analysis to make the result more convincing. Relevant articles published up to 2016 were identified by searching the PubMed database. 13 studies, involving a total of 29405 participants, were included in the meta-analysis. Odds Ratios (ORs) with 95% confidence intervals (CIs) was calculated with random or fixed effects model. All data analyses were analyzed by Review Manger 5.3 software. In Caucasian subgroup: Dominant model (TT + CT vs CC): OR = 1.17 (1.06, 1.29), Recessive model (TT vs CT + CC): OR = 1.25 (1.13, 1.39) and Allele frequency (T vs C): OR = 1.15 (1.08, 1.22). The present meta-analysis suggests that rs3803662 polymorphism is significantly associated with breast cancer risk in Caucasian women, and we did not find the association in Asian women. PMID:27350156

  9. Association of single nucleotide polymorphism rs3803662 with the risk of breast cancer.

    PubMed

    Yang, Yuan; Wang, Wenjing; Liu, Guiyou; Yu, Yingcui; Liao, Mingzhi

    2016-01-01

    Large scale association studies have identified the single nucleotide polymorphism rs3803662 associated with breast cancer risk. However, the sample size of most studies is too small. Here, we performed this meta-analysis to make the result more convincing. Relevant articles published up to 2016 were identified by searching the PubMed database. 13 studies, involving a total of 29405 participants, were included in the meta-analysis. Odds Ratios (ORs) with 95% confidence intervals (CIs) was calculated with random or fixed effects model. All data analyses were analyzed by Review Manger 5.3 software. In Caucasian subgroup: Dominant model (TT + CT vs CC): OR = 1.17 (1.06, 1.29), Recessive model (TT vs CT + CC): OR = 1.25 (1.13, 1.39) and Allele frequency (T vs C): OR = 1.15 (1.08, 1.22). The present meta-analysis suggests that rs3803662 polymorphism is significantly associated with breast cancer risk in Caucasian women, and we did not find the association in Asian women.

  10. Harnessing the complexity of gene expression data from cancer: from single gene to structural pathway methods

    PubMed Central

    2012-01-01

    High-dimensional gene expression data provide a rich source of information because they capture the expression level of genes in dynamic states that reflect the biological functioning of a cell. For this reason, such data are suitable to reveal systems related properties inside a cell, e.g., in order to elucidate molecular mechanisms of complex diseases like breast or prostate cancer. However, this is not only strongly dependent on the sample size and the correlation structure of a data set, but also on the statistical hypotheses tested. Many different approaches have been developed over the years to analyze gene expression data to (I) identify changes in single genes, (II) identify changes in gene sets or pathways, and (III) identify changes in the correlation structure in pathways. In this paper, we review statistical methods for all three types of approaches, including subtypes, in the context of cancer data and provide links to software implementations and tools and address also the general problem of multiple hypotheses testing. Further, we provide recommendations for the selection of such analysis methods. Reviewers This article was reviewed by Arcady Mushegian, Byung-Soo Kim and Joel Bader. PMID:23227854

  11. 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.

  12. Single-port video-assisted thoracic surgery for early lung cancer: initial experience in Japan

    PubMed Central

    Takeuchi, Shingo; Usuda, Jitsuo

    2016-01-01

    Background Single-port video-assisted thoracic surgery (SPVATS) emerged several years ago as a new, minimally invasive surgery for diseases in the field of respiratory surgery, and is increasingly becoming a subject of interest for some thoracic surgeons in Europe and Asia. However, the adoption rate of this procedure in the United States and Japan remains low. We herein reviewed our experience of SPVATS for early lung cancer in our center, and evaluated the safety and minimal invasiveness of this technique. Methods We retrospectively analyzed patients who had undergone SPVATS for pathological stage I lung cancer in Nippon Medical School Chiba Hokusoh Hospital between September 2012 and October 2015. In SPVATS, an approximately 4-cm incision was made at the 4th or 5th intercostal space between the anterior and posterior axillary lines. A rib spreader was not used at the incision site, and surgical manipulation was performed very carefully in order to avoid contact between surgical instruments and the intercostal nerves. The same surgeon performed surgery on all patients, and analyzed laboratory data before and after surgery. Results Eighty-four patients underwent anatomical lung resection for postoperative pathological stage I lung cancer. The mean wound length was 4.2 cm. Eighty-four patients underwent lobectomy and segmentectomy, respectively. The mean preoperative forced expiratory volume in 1 second (FEV1%) was 1.85%±0.36%. Our patients consisted of 49 men (58.3%) and 35 women (41.7%), with 64, 18, 1, and 1 having adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and small-cell lung cancer, respectively. The mean operative time was 175±21 min, operative blood loss 92±18 mL, and duration of drain placement 1.9±0.6 days. The duration of the postoperative hospital stay was 7.1±1.7 days, numeric rating scale (NRS) 1 week after surgery 2.8±0.6, and occurrence rate of allodynia 1 month after surgery 10.7%. No patient developed serious

  13. 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.

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

    PubMed

    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

    2016-10-01

    Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report 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 rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated 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

  15. 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. PMID:26386690

  16. 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.

  17. 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)

  18. 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

  19. A single nucleotide polymorphism in the promoter region of let-7 family is associated with lung cancer risk in Chinese.

    PubMed

    Shen, L Q; Xie, Y Z; Qian, X F; Zhuang, Z X; Jiao, Y; Qi, X F

    2015-01-01

    Lung cancer is a complex polygenic disease and many genetic factors are involved in the development of the disease. As one of the most important and widely studied families of microRNA, let-7 appears to play an important role in initiation and progression of lung cancer. Any small changes in miRNA level or its target point can cause significant changes in gene function. In this study, we examined whether a single-nucleotide polymorphism in the promoter region of the let-7 family (rs10877887) is associated with the susceptibility to and prognosis of lung adenocarcinoma cancer. A hospital-based case-control research model was used in our study. The single-nucleotide polymorphism was genotyped in 69 lung cancer patients and 75 healthy controls by direct sequencing. The correlation between rs10877887 genotypes and the susceptibility to lung cancer was evaluated using an unconditional logistic regression model. Populations with the CT+CC genotype had a significantly increased AC risk compared to those with the TT genotype (CT+CC vs TT: P = 0.043, OR = 2.032, 95%CI = 1.018-4.054). Furthermore, the risk effect was greater in subgroups of females over 60 years old (CT+CC vs TT: OR = 6.857, 95%CI = 1.425-33.008, P = 0.012), and the C allele were confirmed to be a risk factor related to lung cancer in these females (P = 0.012). The single-nucleotide polymorphism rs10877887 in the promoter region of the let-7 family was found to be responsible for the susceptibility to lung adenocarcinoma cancer in Chinese individuals. This association was significantly stronger in females who were more than 60 years old.

  20. Single-Port Laparoscopic Proximal Gastrectomy with Double Tract Reconstruction for Early Gastric Cancer: Report of a Case

    PubMed Central

    Lee, Chang Min; Park, Da Won; Jung, Do Hyun; Jang, You Jin; Kim, Jong-Han; Park, Sungsoo

    2016-01-01

    In Korea, proximal gastrectomy has recently attracted attention as a better choice of function-preserving surgery for proximal early gastric cancer than total gastrectomy. Of the various strategies to overcome reflux symptoms from remnant stomach, double tract reconstruction not only reduces the incidence of anastomosis-related complications, but is also sufficiently reproducible as a laparoscopic procedure. Catching up with the recent rise of single-port laparoscopic surgeries, we performed a pure single-port laparoscopic proximal gastrectomy with DTR. This procedure was designed by merging the function-preserving concept of proximal gastrectomy with single-port laparoscopic total gastrectomy. PMID:27752399

  1. 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

  2. Survival of patients with metastatic breast cancer: a single-centre experience.

    PubMed

    D'hondt, R; Spoormans, I; Neyens, N; Mortier, N; Van Aelst, F

    2014-06-01

    Metastatic breast cancer (MBC) remains an incurable disease, despite major advances in the treatment in the past 10-12 years. Data on real life overall survival in a non-selected group containing all metastatic breast cancer patients are hard to find in the literature, as is the correlation of their survival with prognostic factors and treatment. This article provides overall survival data for all patients treated for MBC in a single-centre non-academic hospital. Survival data have been correlated with frequently used prognostic factors (subtype, age at diagnosis, M-status at diagnosis, metastases-free interval, and grade). It also gives an insight in the treatments given to and response rates in this population of MBC patients without selection bias representing the real life situation. A total of 169 patients were analysed. Mean survival from metastases is 31·8 months. Overall survival is better for the luminal subtypes, for younger age, for patients with a longer metastases-free interval, and for a lower grade. A small difference in survival has been seen in favour of the patients who represent immediately with metastases. With a larger sample size, we expect these factors to be prognostic significant. The luminal subtypes have a clear predisposition to metastasize in the bone, whereas visceral metastases occur more frequently and earlier in the hormone receptor-negative tumours. Brain metastases do occur in about half of the triple negative tumours and Her2/neu-positive tumours. Overall response rate to first-line chemotherapy was 56% in consecutive lines of treatment, a continuous clinical benefit exceeding 50% when selecting fit patients. This article represents a unique and valuable description of medical oncologists' real-life daily practice in MBC patients, with a clinical outcome that certainly compares to the sparse data provided in the literature. PMID:24641516

  3. 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. PMID:27592481

  4. 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

  5. Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk.

    PubMed

    Enokida, Yasuaki; Shimizu, Kimihiro; Kakegawa, Seiichi; Atsumi, Jun; Takase, Yoshiaki; Miyamae, Yohei; Nagashima, Toshiteru; Ohtaki, Yoichi; Kaira, Kyoichi; Sunaga, Noriaki; Yanagitani, Noriko; Yoshino, Reiko; Tsunekawa, Katsuhiko; Igai, Hitoshi; Kamiyoshihara, Mitsuhiro; Usui, Kengo; Lezhava, Alexander; Tomizawa, Yoshio; Ishikawa, Toshihisa; Murakami, Masami; Hayashizaki, Yoshihide; Takeyoshi, Izumi

    2014-09-01

    Murine double minute 2 (MDM2) is a negative regulator of p53. A single-nucleotide polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene has been shown to result in higher levels of MDM2 RNA and protein. Regarding the contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous studies are conflicting. In order to evaluate the association between c.309T>G and the lung cancer risk, a case-control study was performed. The MDM2 genotypes were determined in 762 lung cancer patients and in 700 cancer-free control subjects using the Smart Amplification Process. Statistical adjustment was performed for gender, age and pack-years of smoking. The distributions of c.309T>G (T/T, T/G, G/G) were 20.1, 49.7, 30.2% in the case group and 21.7, 47.9, 30.4% in the healthy-control group. There were no overall associations between the MDM2 genotypes and the risk of lung cancer [T/G genotype: Adjusted odds ratio (AOR), 1.30; 95% confidence interval (CI), 0.88-1.93; and G/G genotype: AOR, 1.18; 95% CI, 0.78-1.80]. The subgroup analysis of gender, histology, smoking status and epidermal growth factor receptor mutation status also indicated that there was no association with lung cancer. Additionally, the genotypes did not have an effect on the age at the time of diagnosis of lung cancer (P=0.25). In conclusion, the G allele frequency in the lung cancer cases was 0.551, which was similar to other studies. The results of the present study suggest that the c.309T>G is not significantly associated with lung cancer.

  6. 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. PMID:26746583

  7. 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.

  8. Simultaneous Quantitation of Na(+) and K(+) in Single Normal and Cancer Cells Using a New Near-Infrared Fluorescent Probe.

    PubMed

    Li, Lu; Li, Ping; Fang, Juan; Li, Qingling; Xiao, Haibin; Zhou, Hui; Tang, Bo

    2015-06-16

    Considering the important functions of cellular Na(+) and K(+) together with their cooperative efforts on various biological processes, it is significant to simultaneously detect Na(+) and K(+) at a single-cell level. Here, we present a novel method to discriminate and quantify simultaneously Na(+) and K(+) in single cells using a new near-infrared fluorescent probe associated with microchip electrophoresis. The fluorescent probe selectively responds to both Na(+) and K(+). The microchip electrophoresis allows accurate single-cell manipulation and effective distinction of Na(+) and K(+). Based on the method, the concentration of Na(+) and K(+) in single normal and cancer cells was compared, and the variation of Na(+) and K(+) in single cancer cells during the early stage of apoptotic volume decrease was monitored, which would help us to better understand the critical roles of Na(+) and K(+) in malignant cells and apoptosis. This method has paved a new way for the research of the synergistic function of Na(+) and K(+) in the regulation of various biological processes at a single-cell level. PMID:25973531

  9. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

    PubMed

    Heyn, Chris; Ronald, John A; Ramadan, Soha S; Snir, Jonatan A; Barry, Andrea M; MacKenzie, Lisa T; Mikulis, David J; Palmieri, Diane; Bronder, Julie L; Steeg, Patricia S; Yoneda, Toshiyuki; MacDonald, Ian C; Chambers, Ann F; Rutt, Brian K; Foster, Paula J

    2006-11-01

    Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease. PMID:17029229

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. From randomised trials to rational practice.

    PubMed

    van Gijn, J

    2005-01-01

    From the age of Enlightenment onwards, philosophical thinking has become increasingly influenced by empiricism: observations lead to theories, but experiments are needed to put the reasoning to the test. However, it was not until the middle of the 20th century that well-designed experiments were at last introduced in medical treatment, in the form of randomised controlled clinical trials. This design is now standard in medicine, but in everyday practice a multitude of management decisions must still be taken without good evidence. There are several reasons for this: there may not be a trial at all or only a single trial; trial results may be equivocal; patients may be different from those enrolled in trials; new procedures require practice, or a trial may not be feasible. 'Logical reasoning', with all its fallacies, is still required - not only to fill the gaps in empirical knowledge but also to interpret existing evidence and to plan new trials. In fact, the generation of new knowledge is a continuous, cyclical process in which newly gained insights in pathophysiology give rise to new therapeutic experiments, the results of which generate fresh hypotheses, and so on. Compassion, curiosity and doubt are the essential forces that keep the cycle moving. Conversely, the progress is slowed down by present-day legalism, which distorts investigator accountability and patient autonomy.

  15. 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

  16. Immune Response Gene Expression in Colorectal Cancer Carries Distinct Prognostic Implications According to Tissue, Stage and Site: A Prospective Retrospective Translational Study in the Context of a Hellenic Cooperative Oncology Group Randomised Trial

    PubMed Central

    Pentheroudakis, George; Raptou, Georgia; Kotoula, Vassiliki; Wirtz, Ralph M.; Vrettou, Eleni; Karavasilis, Vasilios; Gourgioti, Georgia; Gakou, Chryssa; Syrigos, Konstantinos N.; Bournakis, Evangelos; Rallis, Grigorios; Varthalitis, Ioannis; Galani, Eleni; Lazaridis, Georgios; Papaxoinis, George; Pectasides, Dimitrios; Aravantinos, Gerasimos; Makatsoris, Thomas; Kalogeras, Konstantine T.; Fountzilas, George

    2015-01-01

    Background Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study. Patients and Methods Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa. Results Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC. Conclusions In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression. Trial Registration ANZCTR.org.au ACTRN

  17. Randomised trials for the Fitbit generation

    PubMed Central

    Dempsey, Walter; Liao, Peng; Klasnja, Pedja; Nahum-Shani, Inbal; Murphy, Susan A.

    2016-01-01

    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. PMID:26807137

  18. Seven myths of randomisation in clinical trials.

    PubMed

    Senn, Stephen

    2013-04-30

    I consider seven misunderstandings that may be encountered about the nature, purpose and properties of randomisation in clinical trials. Some concern the practical realities of clinical research on patients. Others are to do with the value and purpose of balance. Still others are to do with a confusion about the role of conditioning in valid statistical inference. I consider a simple game of chance involving two dice to illustrate some points about inference and then consider the seven misunderstandings in turn. I conclude that although one should not make a fetish of randomisation, when proposing alternatives to randomisation in clinical trials, one should be very careful to be precise about the exact nature of the alternative being considered if one is to avoid the danger of underestimating the advantages that randomisation can offer. PMID:23255195

  19. A single measure of cancer burden combining incidence with mortality rates for worldwide application.

    PubMed

    Kim, Jeong Lim; Cho, Kyoung-Hee; Park, Eun-Cheol; Cho, Woo Hyun

    2014-01-01

    We attempted to develop an indicator combining incidence and mortality (summary indicator of cancer burden, SMCB) and to compare the magnitudes of cancer burden by world region. The SMCB was used to measure the size of cancer burden summarizing the incidence and mortality. The incidence and mortality were divided in equivalent forms and were split. The criteria dividing the size of cancer burden were used as the maximum incidence and mortality by men and women according to the world database, and the value corresponding to 10% of each maximum was set as the cut-off value. In SMCB, the size of cancer burden was highest for men with lung cancer (SMCB=18) and for women with breast cancer (SMCB=14) in MDR (more developed regions) compared to the size of burden in LDR (lower developed regions) (lung, SMCB=11, breast, SMCB=8). For men, the size of cancer burden by region was highest in EURO (SMCB=18, lung), followed by WPRO (SMCB=16, lung), PAHO (SMCB=14, prostate), AFRO (SMCB=8, prostate) and SEARO (SMCB=7, lung). Moreover, for women, the size of cancer burden was greatest in EURO (SMCB=14, breast), followed by PAHO (SMCB=13, breast), AFRO (SMCB=11, cervix uteri), EMRO (SMCB=9, breast) or SEARO (SMCB=8, cervix uteri) and WPRO (SMCB=7, lung). The summary indicator will help to provide a priority setting for reducing cancer burden in health policy.

  20. Green fluorescent-conjugated anti-CEA single chain antibody for the detection of CEA-positive cancer cells.

    PubMed

    Salavatifar, Maryam; Amin, Shadi; Jahromi, Zahra Moghaddassi; Rasgoo, Nasrin; Rastgoo, Nasrin; Arbabi, Mehdi

    2011-06-01

    According to World Health Organization (WHO), cancer is a leading cause of death worldwide, accounting for 7.4 million deaths (around 13% of all deaths) in 2004. Monoclonal/recombinant antibodies, which specifically target clinical biomarkers of disease, have increasingly been applied as powerful tools in cancer imaging and therapy, a fact that is highlighted by some nine FDA-approved monoclonal antibodies (MAbs) or their immunoconjugates (as of December 2008) for use in cancer treatment. In this study, five monoclonal antibodies (MAbs) were generated and characterized against carcinoembryonic antigen (CEA), which is widely used clinically as both a blood and tissue tumor marker of epithelial malignancy. Variable domains (VH and VL) of one the stable MAbs with highest affinity were PCR-amplified and assembled as single-chain antibody fragment (scFv). Following the cloning and expression of scFv antibody fragments in Escherichia coli, the functional binding and specificity of the recombinant antibody were confirmed by ELISA. To develop a direct in vitro detection of CEA-positive cancer cells, scFv DNA was genetically fused to enhanced green fluorescent protein (EGFP) gene and expressed in bacteria. The chimeric fluorescent protein is able to specifically detect CEA-positive cell lines; no cross-reactivity was observed with a negative control cell line. This strategy will likely allow the establishment of a rapid, single-step detection assay of CEA, which is considered to be one of the best predictors of malignancy among all other tumor markers.

  1. Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan.

    PubMed

    Wu, Hsi-Chin; Chang, Chao-Hsiang; Tsai, Ru-Yin; Lin, Chih-Hsueh; Wang, Rou-Fen; Tsai, Chia-Wen; Chen, Kuen-Bao; Yao, Chun-Hsu; Chiu, Chang-Fang; Bau, Da-Tian; Lin, Cheng-Chieh

    2010-09-01

    Prostate cancer is the most common cause of cancer death in men and is a major health problem worldwide. Methylene tetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is also an important source of DNA methylation and DNA synthesis (nucleotide synthesis). To assess the association and interaction of genotypic polymorphisms in MTHFR and lifestyle factors with prostate cancer in Taiwan, we investigated two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), analyzed the association of specific genotypes with prostate cancer susceptibility, and discussed their joint effects with individual habits on prostate cancer risk. In total, 218 patients with prostate cancer and 436 healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped for these polymorphisms with prostate cancer susceptibility. We found the MTHFR C677T but not the A1298C genotype was differently distributed between the prostate cancer and control groups. The T allele of MTHFR C677T conferred a significantly (p=0.0011) decreased risk of prostate cancer. As for the A1298C polymorphism, there was no difference in distribution between the prostate cancer and control groups. Gene interactions with smoking were significant for MTHFR C677T polymorphism. The MTHFR C677T CT and TT genotypes in association with smoking conferred a decreased risk of 0.501 (95% confidence interval=0.344-0.731) for prostate cancer. Our results provide the first evidence that the C allele of MTHFR C677T may be associated with the development of prostate cancer and may be a novel useful marker for primary prevention and anticancer intervention.

  2. Preoperative Single Fraction Partial Breast Radiotherapy for Early-Stage Breast Cancer

    SciTech Connect

    Palta, Manisha; Yoo, Sua; Adamson, Justus D.; Prosnitz, Leonard R.; Horton, Janet K.

    2012-01-01

    Purpose: Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. Methods and Materials: A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A 'virtual plan' was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. Results: The median breast volume was 1,713 cm{sup 3} (range: 1,014-2,140), and the median clinical target volume was 44 cm{sup 3} (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm{sup 3} of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Conclusion: Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing.

  3. 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

  4. 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.

  5. Identification of lung cancer oncogenes based on the mRNA expression and single nucleotide polymorphism profile data.

    PubMed

    Wang, Y; Mei, Q; Ai, Y Q; Li, R Q; Chang, L; Li, Y F; Xia, Y X; Li, W H; Chen, Y

    2015-01-01

    This study aimed to identify the oncogenes associated with lung cancer based on the mRNA and single nucleotide polymorphism (SNP) profile data. The mRNA expression profile data of GSE43458 (80 cancer and 30 normal samples) and SNP profile data of GSE33355 (61 pairs of lung cancer samples and control samples) were downloaded from Gene Expression Omnibus database. Common genes between the mRNA profile and SNP profile were identified as the lung cancer oncogenes. Risk subpathways of the selected oncogenes with the SNP locus were analyzed using the iSubpathwayMiner package in R. Moreover, protein-protein interaction (PPI) network of the oncogenes was constructed using the HPRD database and then visualized using the Cytoscape. Totally, 3004 DEGs (1105 up-regulated and 1899 down-regulated) and 125 significant SNPs closely related to 174 genes in the lung cancer samples were identified. Also, 39 common genes, like PFKP (phosphofructokinase, platelet) and DGKH-rs11616202 (diacylglycerol kinase, eta) that enriched in sub-pathways such as galactose metabolism, fructose and mannose metabolism, and pentose phosphate pathway, were identified as the lung cancer oncogenes. Besides, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1), RORA (RAR-related orphan receptor A), MAGI3 (membrane associated guanylate kinase, WW and PDZ domain containing 3), PTPRM (protein tyrosine phosphatase, receptor type, M), and BMP6 (bone morphogenetic protein 6) were the hub genes in PPI network. Our study suggested that PFKP and DGKH that enriched in galactose metabolism, fructose and mannose metabolism pathway, as well as PIK3R1, RORA, and MAGI3, may be the lung cancer oncogenes.

  6. Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients.

    PubMed

    Wang, Xu-shi; Song, Hai-bin; Chen, Si; Zhang, Wei; Liu, Jia-qi; Huang, Chao; Wang, Hao-ran; Chen, Yuan; Chu, Qian

    2015-10-01

    Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

  7. 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

  8. 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

  9. The Outcomes of Esophageal and Gastric Cancer Treatments in a Retrospective Study, Single Center Experience

    PubMed Central

    Jalali, Arash; Aliabadi, Leyla Sharifi; Ghaffari, Fatemeh; Maheri, Roghieh; Eini, Ezzat; Mashhadireza, Maryam; Mousavi, Seied Asadollah; Bahar, Babak; Jahani, Mohammad; Ghavamzadeh, Ardeshir

    2014-01-01

    Introduction Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients. Methods In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011. Results The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 – 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 – 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 – 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 – 67.3%), 32.8% (95% CI: 22.1 – 48.7%), and 56.7% (95% CI: 50.1 – 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 – 69.8%), 39.5% (95 CI: 28.1 – 55.5%), and 68.2% (95% CI: 61.8 – 75.3%), respectively (p < 0.001). Conclusion Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease

  10. 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.

  11. 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

  12. The impact of diabetes mellitus on breast cancer outcomes: a single center retrospective study.

    PubMed

    Yerrabothala, Swaroopa; Shaaban, Hamid; Capo, Gerardo; Maroules, Michael; Debari, Vincent A

    2014-01-01

    Diabetes mellitus has been implicated to affect the prognostic outcomes of patients with various types of cancer. This study explores the impact of diabetes mellitus on the survival outcomes of patients with all stages of breast cancer. We performed a retrospective analysis of 255 patients with all stages of breast cancer. Survival outcomes were compared for diabetic and non-diabetic patients. A greater percent of patients in the non-diabetic group (54.1%) presented with early-stage (stage 0 and 1) cancer than diabetics for which 41.2% presented with stage 0 or 1 breast cancer; however this difference did not achieve statistical significance (p = 0.068). Overall, we observed a significant difference in survival between the diabetics and non-diabetic subjects (p = 0.001). Even after adjustment for all covariates and after stratification for Body Mass Index (BMI), diabetics were found to have a poorer prognosis in terms of survival time. In patients with breast cancer, diabetes mellitus is an independent predictor of lower overall survival rates, even after adjusting for other comorbidities. Primary caregivers and oncologists alike should aggressively screen breast cancer patients for diabetes mellitus and vice versa. PMID:23832821

  13. 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.

  14. 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

  15. Salvage chemoradiotherapy after primary chemotherapy for locally advanced pancreatic cancer: a single-institution retrospective analysis

    PubMed Central

    2012-01-01

    Background There is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC. Methods Thirty patients who underwent salvage CRT, after the failure of primary chemotherapy for LAPC, were retrospectively enrolled from 2004 to 2011 at the authors’ institution. All the patients had histologically confirmed pancreatic adenocarcinoma. Results Primary chemotherapy was continued until progression or emergence of unacceptable toxicity. Eventually, 26 patients (87%) discontinued primary chemotherapy because of local tumor progression, whereas four patients (13%) discontinued chemotherapy because of interstitial pneumonitis caused by gemcitabine. After a median period of 7.9 months from starting chemotherapy, 30 patients underwent salvage CRT combined with either S-1 or 5-FU. Toxicities were generally mild and self-limiting. Median survival time (MST) from the start of salvage CRT was 8.8 months. The 6 month, 1-year and 2-year survival rates from the start of CRT were 77%, 33% and 26%, respectively. Multivariate analysis revealed that a lower pre-CRT serum CA 19–9 level (≤ 1000 U/ml; p = 0.009) and a single regimen of primary chemotherapy (p = 0.004) were independent prognostic factors for survival after salvage CRT. The MST for the entire patient population from the start of primary chemotherapy was 17.8 months, with 2- and 3-year overall survival rates of 39% and 22%, respectively. Conclusions CRT had moderate anti-tumor activity and an acceptable toxicity profile in patients with LAPC, even after failure of gemcitabine-based primary chemotherapy. If there are any signs of failure of primary chemotherapy without distant metastasis

  16. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy.

    PubMed

    Jørgensen, Jesper Tranekjær; Norregaard, Kamilla; Tian, Pengfei; Bendix, Poul Martin; Kjaer, Andreas; Oddershede, Lene B

    2016-08-02

    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 ((18)F-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.

  17. Learning curve for single-incision laparoscopic resection of right-sided colon cancer by complete mesocolic excision

    PubMed Central

    Kim, Chang Woo; Han, Yun Dae; Kim, Ha Yan; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Abstract Single-incision laparoscopic surgery is cosmetically beneficial, but technically challenging. In this study, the learning curve (LC) for single-incision laparoscopic right hemicolectomy (SILRC), incorporating complete mesocolic excision to resect right-sided colon cancer, was investigated through multidimensional techniques. Between December 2009 and May 2015, 64 patients each underwent SILRC of right-sided colon cancer at Severance Hospital, performed in all instances by the same surgeon. Moving average and cumulative sum control chart (CUSUM) were used for LC analyses retrospectively. Surgical failure was defined as conversion to conventional laparoscopic surgery, postsurgical morbidity within 30 days, harvested lymph node count <12, or local tumor recurrence. Both moving average and CUSUM graphics of operative time registered nadirs at the 24th patient, with slight ascent thereafter, reaching a plateau at the 40th patient. The CUSUM for surgical success peaked at the 23rd patient. Operative time for 23 patients in phase 1 (1–23) and for 41 patients in phase 2 (24–64) of the LC did not differ significantly. By comparison, significant differences in patients of phase 2 included larger tumor size, higher harvested lymph node counts, longer proximal resection margins, and more advanced disease. As indicated by multidimensional statistical analyses, the LC for SILRC of right-sided colon cancer was 23 patients. In terms of operative time and surgical success, SILRC is feasible for surgeons experienced in LS, but may prove more challenging for novices, given the fundamental technical difficulties of this procedure. PMID:27367999

  18. 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.

  19. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy.

    PubMed

    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 ((18)F-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

  20. 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

  1. Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics.

    PubMed

    Burke, Russell T; Orth, James D

    2016-01-01

    The response of single cells to anti-cancer drugs contributes significantly in determining the population response, and therefore is a major contributing factor in the overall outcome. Immunoblotting, flow cytometry and fixed cell experiments are often used to study how cells respond to anti-cancer drugs. These methods are important, but they have several shortcomings. Variability in drug responses between cancer and normal cells, and between cells of different cancer origin, and transient and rare responses are difficult to understand using population averaging assays and without being able to directly track and analyze them longitudinally. The microscope is particularly well suited to image live cells. Advancements in technology enable us to routinely image cells at a resolution that enables not only cell tracking, but also the observation of a variety of cellular responses. We describe an approach in detail that allows for the continuous time-lapse imaging of cells during the drug response for essentially as long as desired, typically up to 96 hr. Using variations of the approach, cells can be monitored for weeks. With the employment of genetically encoded fluorescent biosensors numerous processes, pathways and responses can be followed. We show examples that include tracking and quantification of cell growth and cell cycle progression, chromosome dynamics, DNA damage, and cell death. We also discuss variations of the technique and its flexibility, and highlight some common pitfalls. PMID:27213923

  2. 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

    2015-01-01

    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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. The role of depression in the development of breast cancer: analysis of registry data from a single institute.

    PubMed

    Montazeri, Ali; Jarvandi, Soghra; Ebrahimi, Mandana; Haghighat, Shahpar; Ansari, Mariam

    2004-01-01

    Although controversial, the belief that developing breast cancer may be associated with psychological distress is not uncommon. The present study examined the role of psychological variables in the development of breast cancer in women attending a breast clinic for medical examination in Tehran, Iran. During a three-year period (1997-1999) a trained female nurse interviewed all women attending the Iranian Center for Breast Cancer (ICBC) before a confirmed diagnosis was made (N = 3000). Data were collected on demographic variables (age, education and marital status), known risk factors (age at menarche, age at first time full term pregnancy, family history of breast cancer, menopausal status, and oral contraceptive use), psychological variables, including history of psychiatric medications, depression (depressed mood, hopelessness, and loss of interests and pleasures), anxiety (mental and somatic signs) and two single measures of overall health and quality of life. In all, 243 patients were diagnosed as having breast cancer. A total of 486 patients with benign disease were randomly selected from the original cohort as controls. Univariate and multivariate logistic regression analyses were performed to determine the predictive effect of each factor on the risk of breast cancer. There were no significant differences between cases and controls except for age at menarche (P = 0.007) and family history of breast cancer (P<0.001). With regard to psychological variables studied, the results showed that there were significant differences between cases and controls regarding depression (depressed mood P<0.0001, hopelessness P = 0.001, and loss of interest and pleasures P = 0.001), and anxiety (mental signs P = 0.006). Finally, after performing multiple logistic regression analysis in addition to family history and age at menarche, depressed mood and hopelessness showed significant results (odds ratios of 1.90, and 1.63 respectively). The findings of the present study suggest

  8. Statistical Issues for Design and Analysis of Single-Arm Multi-Stage Phase II Cancer Clinical Trials

    PubMed Central

    Jung, Sin-Ho

    2015-01-01

    Summary Phase II trials have been very widely conducted and published every year for cancer clinical research. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. Because of their small sample sizes, statistical methods based on large sample approximation are not appropriate for design and analysis of phase II trials. As a prospective clinical research, the analysis method of a phase II trial is predetermined at the design stage and it is analyzed during and at the end of the trial as planned by the design. The analysis method of a trial should be matched with the design method. For two-stage single arm phase II trials, Simon's method has been the standards for choosing an optimal design, but the resulting data have been analyzed and published ignoring the two-stage design aspect with small sample sizes. In this article, we review analysis methods that exactly get along with the exact two-stage design method. We also discuss some statistical methods to improve the existing design and analysis methods for single-arm two-stage phase II trials. PMID:25749311

  9. 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.

  10. 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

  11. Comprehensive detection of diverse exon 19 deletion mutations of EGFR in lung Cancer by a single probe set.

    PubMed

    Bae, Jin Ho; Jo, Seong-Min; Kim, Hak-Sung

    2015-12-15

    Detection of exon 19 deletion mutation of EGFR, one of the most frequently occurring mutations in lung cancer, provides the crucial information for diagnosis and treatment guideline in non-small-cell lung cancer (NSCLC). Here, we demonstrate a simple and efficient method to detect various exon 19 deletion mutations of EGFR using a single probe set comprising of an oligo-quencher (oligo-Q) and a molecular beacon (MB). While the MB hybridizes to both the wild and mutant target DNA, the oligo-Q only binds to the wild target DNA, leading to a fluorescent signal in case of deletion mutation. This enables the comprehensive detection of the diverse exon 19 deletion mutations using a single probe set. We demonstrated the utility and efficiency of the approach by detecting the frequent exon 19 deletion mutations of EGFR through a real-time PCR and in situ fluorescence imaging. Our approach enabled the detection of genomic DNA as low as 0.02 ng, showing a detection limit of 2% in a heterogeneous DNA mixture, and could be used for detecting mutations in a single cell level. The present MB and oligo-Q dual probe system can be used for diagnosis and treatment guideline in NSCLC.

  12. Magnetic and fluorescent graphene for dual modal imaging and single light induced photothermal and photodynamic therapy of cancer cells.

    PubMed

    Gollavelli, Ganesh; Ling, Yong-Chien

    2014-05-01

    Developing a simple and cost-effective strategy to diagnose and treat cancer with single and minimal dosage through noninvasive strategies are highly challenging. To make the theranostic strategy effective, single light induced photothermal and photodynamic reagent with dual modal imaging capability is highly desired. Herein, a simple non-covalent approach was adopted to immobilize hydrophobic silicon napthalocyanine bis (trihexylsilyloxide) (SiNc4) photosensitizer onto water dispersible magnetic and fluorescent graphene (MFG) via π-π stacking to yield MFG-SiNc4 functioned as a theranostic nanocarrier. Taking the advantage of broad near infra-red absorption (600-1200 nm) by graphene, photosensitizer of any wavelength within this range will facilitate the single light induced phototherapy. Phosphorescence spectra, singlet oxygen sensor green (SOSG) experiments, and 1,3-diphenyl isobenzofuran quenching studies confirm the generation of singlet (1)O2 upon photoirradiation. Confocal microscopic images reveal successful internalization of MFG-SiNc4 in HeLa cells; whereas T2-weighted magnetic resonance images of MFG reveal a significant concentration dependent darkening effect. In vitro photodynamic/photothermal therapeutic studies on HeLa cells have demonstrated that the killing efficacy of MFG-SiNc4 using a single light source is ∼97.9%, presumably owing to the combined effects of generating reactive oxygen species, local heating, and induction of apoptosis. The developed MFG-SiNc4 may thus be utilized as a potential theranostic nanocarrier for dual modal imaging and phototherapy of cancer cells with single light source for time and cost effective treatments with a minimal therapy dose.

  13. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

    PubMed

    Nissenbaum, M; Browde, S; Bezwoda, W R; de Moor, N G; Derman, D P

    1984-01-01

    Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

  14. Association between a single nucleotide polymorphism in the TP53 region and risk of ovarian cancer.

    PubMed

    Xi, Yanni; Liu, Congrong; Xin, Xiaoyan

    2014-12-01

    TP53 is known as a tumor suppressor gene involved in cell cycle regulation. Many previous epidemiological and clinical studies have evaluated the effects of rs1042522 polymorphism on risk of ovarian cancer. But the results are conflicting and heterogeneous. The primary objective of this study was to examine whether rs1042522 polymorphism is associated with ovarian cancer risk. We performed a comprehensive meta-analysis of 19 case-control studies that analyzed rs1042522 polymorphism in ovarian cancer risk. Odds ratios (ORs) were calculated using distinct genetic models. Heterogeneity between studies was detected by the χ(2)-based Q test. Additional analyses such as sensitivity analyses and publication bias were also performed. The rs1042522 polymorphism was not overall associated with ovarian cancer risk. But there was a borderline association in the heterozygote model (OR = 1.09, 95 % CI 0.99-1.21). Similar effects were observed in the subgroup of Caucasian population (the heterozygote model: OR = 1.11, 95 % CI 1.00-1.24). No significant heterogeneity and publication bias were revealed in this meta-analysis. This study provides statistical evidence that TP53 rs1042522 polymorphism may play a role in modulating risk of ovarian cancer. This observation requires further analysis of a larger study size.

  15. 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

  16. 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

  17. 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.

  18. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options.

    PubMed

    Rodrigues, Daniela; Longatto-Filho, Adhemar; Martins, Sandra F

    2016-01-01

    Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. PMID:27563673

  19. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

    PubMed Central

    Rodrigues, Daniela; Longatto-Filho, Adhemar

    2016-01-01

    Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. PMID:27563673

  20. 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

  1. Breast cancer risk, dietary intake, and methylenetetrahydrofolate reductase (MTHFR)single nucleotide polymorphisms.

    PubMed

    Alshatwi, Ali A

    2010-07-01

    Diet plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C-->T), resulting in allozymes with altered activity and is thus believed to cause interindividual differences in cancer risk susceptibility. I evaluated this polymorphism and its effect on the food intake and breast cancer risk association in a population-based case-control study of 100 breast cancer cases and 100 controls using a real-time PCR based assay. All subjects completed in-person interviews, which included a food-frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution ofMTHFRpolymorphisms at codon 677 (41.4% cases and 41.8% controls carried theTallele). An inverse association of breast cancer risk with food intake was observed in all genotype groups, particularly among subjects with the677TTgenotype. Compared with those with the677CCgenotype and high food intake frequency, the adjusted odds ratios (95% confidence intervals) associated with low food intake were 1.94 (1.15-3.26), 2.17 (1.34-3.51), and 2.51 (1.37-4.60) for subjects who hadCC,CT, andTTgenotypes (Pfor interaction, 0.05). Results of this study suggest that theMTHFR C677T polymorphism may modify the association between dietary intake and breast cancer risk. PMID:20417243

  2. Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment

    PubMed Central

    Paiva, Cláudia; Garcia, José; Araújo, Alexandra; Araújo, António

    2016-01-01

    Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence. PMID:27781130

  3. Efficient analysis of a small number of cancer cells at the single-cell level using an electroactive double-well array.

    PubMed

    Kim, Soo Hyeon; Fujii, Teruo

    2016-07-01

    Analysis of the intracellular materials of a small number of cancer cells at the single-cell level is important to improve our understanding of cellular heterogeneity in rare cells. To analyze an extremely small number of cancer cells (less than hundreds of cells), an efficient system is required in order to analyze target cells with minimal sample loss. Here, we present a novel approach utilizing an advanced electroactive double-well array (EdWA) for on-chip analysis of a small number of cancer cells at the single-cell level with minimal loss of target cells. The EdWA consisted of cell-sized trap-wells for deterministic single-cell trapping using dielectrophoresis and high aspect ratio reaction-wells for confining the cell lysates extracted by lysing trapped single cells via electroporation. We demonstrated a highly efficient single-cell arraying (a cell capture efficiency of 96 ± 3%) by trapping diluted human prostate cancer cells (PC3 cells). On-chip single-cell analysis was performed by measuring the intracellular β-galactosidase (β-gal) activity after lysing the trapped single cells inside a tightly enclosed EdWA in the presence of a fluorogenic enzyme substrate. The PC3 cells showed large cell-to-cell variations in β-gal activity although they were cultured under the same conditions in a culture dish. This simple and effective system has great potential for high throughput single-cell analysis of rare cells.

  4. 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

  5. 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

  6. Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.

    PubMed

    Hernández-Caballero, Marta Elena; Sierra-Ramírez, José Alfredo

    2015-03-01

    The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

  7. 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

  8. Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?

    PubMed Central

    Carr, Antony M.

    2016-01-01

    Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites. PMID:27688957

  9. Longitudinal tracking of single live cancer cells to understand cell cycle effects of the nuclear export inhibitor, selinexor

    PubMed Central

    Marcus, Joshua M.; Burke, Russell T.; DeSisto, John A.; Landesman, Yosef; Orth, James D.

    2015-01-01

    Longitudinal tracking is a powerful approach to understand the biology of single cells. In cancer therapy, outcome is determined at the molecular and cellular scale, yet relationships between cellular response and cell fate are often unknown. The selective inhibitor of nuclear export, selinexor, is in development for the treatment of various cancers. Selinexor covalently binds exportin-1, causing nuclear sequestration of cargo proteins, including key regulators of the cell cycle and apoptosis. The cell cycle effects of selinexor and the relationships between cell cycle effects and cell fates, has not been described for individual cells. Using fluorescent cell cycle indicators we report the majority of cell death after selinexor treatment occurs from a protracted G1-phase and early S-phase. G1- or early S-phase treated cells show the strongest response and either die or arrest, while those treated in late S- or G2-phase progress to mitosis and divide. Importantly, the progeny of cell divisions also die or arrest, mostly in the next G1-phase. Cells that survive selinexor are negative for multiple proliferation biomarkers, indicating a penetrant, arrested state. Selinexor acts quickly, shows strong cell cycle selectivity, and is highly effective at arresting cell growth and inducing death in cancer-derived cells. PMID:26399741

  10. Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?

    PubMed Central

    Carr, Antony M.

    2016-01-01

    Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites.

  11. 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

  12. Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.

    PubMed

    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

  13. DigiPINS: a database for vertebrate exonic single nucleotide polymorphisms and its application to cancer association studies.

    PubMed

    Navratil, Vincent; Penel, Simon; Delmotte, Stéphane; Mouchiroud, Dominique; Gautier, Christian; Aouacheria, Abdel

    2008-04-01

    Single nucleotide polymorphisms (SNPs), which are the most abundant form of genetic variations in numerous organisms, have emerged as important tools for the study of complex genetic traits and deciphering of genome evolution. High-throughput genome sequencing projects worldwide provide an unprecedented opportunity for whole-genome SNP analysis in a variety of species. To facilitate SNP discovery in vertebrates, we have developed a web-based, user-friendly, and fully automated application, DigiPINS, for genome-wide identification of exonic SNPs from EST data. Currently, the database can be used to the mining of exonic SNPs in six complete genomes (Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus and Danio rerio). In addition to providing information on sequence conservation, DigiPINS allows compilation of comprehensive sets of polymorphisms within cancer candidate genes or identification of novel cancer markers, making it potentially useful for cancer association studies. The DigiPINS server is available via the internet at http://pbil.univ-lyon1.fr/gem/DigiPINS/query_DigiPINS.php.

  14. 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.

  15. Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment

    PubMed Central

    Rana, Suresh; Cheng, ChihYao

    2013-01-01

    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. PMID:23845140

  16. 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.

  17. Limits of Bioparticle Detection in NanoLaser Microfluidic Chips and Application to Cancer Detection in Single Cells and Mitochondria

    NASA Astrophysics Data System (ADS)

    Gourley, Paul L.; Gourley, Brett A.

    2010-03-01

    BioChips comprising light-emitting semiconductors can be configured as microfluidic laser cavities used for ultrafast analysis of bioparticles such as whole cells, organelles, virons, and macromolecules (protein,DNA,RNA). Three regimes of operation include: 1.Geometrical limit (particle radius a>>λ the laser wavelength), laser exhibits multimode spectra useful to study particle morphology, shape, and composition. 2. Mie regime (a λ) laser exhibits nano-squeezed light with single mode operation to study particle size and composition. 3.Rayleigh limit (a<<λ) laser exhibits cavity mode fluctuations to study nanoparticle mass and motion. We have recently used these biochips to study the nanolaser spectra of submicron mitochondrial bioparticles as a new probe of cancer in single cells. These high-speed, nanophotonic tools may play an important role in advancing early detection of cancer and offer improvements over conventional tumor pathology that relies on labor-intensive microscopic examination and/or older cell-staining methods that can be time-consuming and may give false readings.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. Lung Cancer in Homeless People: Clinical Outcomes and Cost Analysis in a Single Institute

    PubMed Central

    Suh, Koung Jin; Kim, Ki Hwan; Lim, Jin; Park, Jin Hyun; Kim, Jin-Soo

    2016-01-01

    Introduction. To characterize the demographic and clinical features, outcomes, and treatment costs of lung cancer in homeless people. Methods. Medical records of 22 homeless patients with lung cancer at Seoul National University Boramae Medical Center in Seoul, South Korea, were retrospectively analyzed. Results. All patients were men (median age, 62 years). Most patients (78%) had advanced disease (stage IIIB, n = 2; stage IV, n = 15). Seven died during initial hospitalization (median survival, 1.5 months). Six were lost to follow-up after initial outpatient visits or discharges from initial admission (median follow-up, 13 days). Only 4 received appropriate treatment for their disease and survived for 1, 15, 19, and 28 months, respectively. Conversely, 4 of 5 patients with early stage disease (stage I, n = 4; stage IIA, n = 1) received curative surgery (median follow-up 25.5 months). The median treatment cost based on 29 days of hospitalization and 2 outpatient visits was $12,513, constituting 47.3% of the 2013 per capita income. Inpatient treatment accounted for 90% of the total costs. The National Health Insurance Service paid 82% of the costs. Conclusion. Among the homeless, lung cancer seems to be associated with poor prognosis and substantial costs during a relatively short follow-up and survival period. PMID:27445531

  3. MicroRNA let-7: Regulation, single nucleotide polymorphism, and therapy in lung cancer.

    PubMed

    Yang, Guang; Zhang, Wenqi; Yu, Chunlei; Ren, Jin; An, Zhe

    2015-08-01

    Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are highly evolutionarily conserved noncoding small RNAs, which were first identified in Caenorhabditis elegans. There are 1100 or more miRNAs have been identified in Homo sapiens. Let-7 miRNA is involved in the regulation of gene expression in cells. Several novel factors and feedback loops involved in the regulation of the synthesis of let-7 have been identified and additional let-7 target genes have been found. Let-7 has also been shown to be significantly correlated with the occurrence and development of cancer and the results of preliminary studies suggest that it is involved in the regulation of oncogenic pathways in numerous types of tumors, such as, LC. As let-7 is a potential molecular target for tumor therapy, a mass of studies have been conducted focus on the relationship between let-7 and LC. With the mechanism becoming revealed, more and more groups are looking for the anti-tumor role of let-7 family in anti-tumor therapy development. In this review, we summarize the newest investigations on let-7 and LC, the regulation of let-7 and its targets gene have been discussed, and the attempts for new therapy for LC have also been summarized.

  4. 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

  5. Cancer

    MedlinePlus

    ... your life Being exposed to chemicals that can cause cancer Being at risk for skin cancer Depending on ... than nonsmokers. Other forms of tobacco can also cause cancer, such as cigars, chewing tobacco and snuff. If ...

  6. 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

  7. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.

    PubMed

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; Singhal, Sharad S

    2011-11-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.

  8. 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

  9. 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.

  10. Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers.

    PubMed

    Martinez, Emmanuelle; Silvy, Françoise; Fina, Fréderic; Bartoli, Marc; Krahn, Martin; Barlesi, Fabrice; Figarella-Branger, Dominique; Iovanna, Juan; Laugier, René; Ouaissi, Mehdi; Lombardo, Dominique; Mas, Eric

    2015-11-24

    Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present.

  11. FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study

    PubMed Central

    Rombouts, SJ; Mungroop, TH; Heilmann, MN; van Laarhoven, HW; Busch, OR; Molenaar, IQ; Besselink, MG; Wilmink, JW

    2016-01-01

    Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.

  12. Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers

    PubMed Central

    Martinez, Emmanuelle; Silvy, Françoise; Fina, Fréderic; Bartoli, Marc; Krahn, Martin; Barlesi, Fabrice; Figarella-Branger, Dominique; Iovanna, Juan; Laugier, René; Ouaissi, Mehdi; Lombardo, Dominique; Mas, Eric

    2015-01-01

    Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present. PMID:26498142

  13. HER2 mutated breast cancer responds to treatment with single agent neratinib, a second generation HER2/EGFR tyrosine kinase inhibitor

    PubMed Central

    Ben–Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M.; Ma, Cynthia X.; Ellis, Matthew J.

    2015-01-01

    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. In this case report, we describe 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 function 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 is 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 cancer, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2 mutated solid tumors is warranted. PMID:26358790

  14. Evaluation of Intermittent Hemodialysis in Critically Ill Cancer Patients with Acute Kidney Injury Using Single-Pass Batch Equipment

    PubMed Central

    Torres da Costa e Silva, Verônica; Costalonga, Elerson C.; Oliveira, Ana Paula Leandro; Hung, James; Caires, Renato Antunes; Hajjar, Ludhmila Abrahão; Fukushima, Julia T.; Soares, Cilene Muniz; Bezerra, Juliana Silva; Oikawa, Luciane; Yu, Luis; Burdmann, Emmanuel A.

    2016-01-01

    Background Data on renal replacement therapy (RRT) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) is scarce. The aim of this study was to assess the safety and the adequacy of intermittent hemodialysis (IHD) in critically ill cancer patients with AKI. Methods and Findings In this observational prospective cohort study, 149 ICU cancer patients with AKI were treated with 448 single-pass batch IHD procedures and evaluated from June 2010 to June 2012. Primary outcomes were IHD complications (hypotension and clotting) and adequacy. A multiple logistic regression was performed in order to identify factors associated with IHD complications (hypotension and clotting). Patients were 62.2 ± 14.3 years old, 86.6% had a solid cancer, sepsis was the main AKI cause (51%) and in-hospital mortality was 59.7%. RRT session time was 240 (180–300) min, blood/dialysate flow was 250 (200–300) mL/min and UF was 1000 (0–2000) ml. Hypotension occurred in 25% of the sessions. Independent risk factors (RF) for hypotension were dialysate conductivity (each ms/cm, OR 0.81, CI 0.69–0.95), initial mean arterial pressure (each 10 mmHg, OR 0.49, CI 0.40–0.61) and SOFA score (OR 1.16, CI 1.03–1.30). Clotting and malfunctioning catheters (MC) occurred in 23.8% and 29.2% of the procedures, respectively. Independent RF for clotting were heparin use (OR 0.57, CI 0.33–0.99), MC (OR 3.59, CI 2.24–5.77) and RRT system pressure increase over 25% (OR 2.15, CI 1.61–4.17). Post RRT blood tests were urea 71 (49–104) mg/dL, creatinine 2.71 (2.10–3.8) mg/dL, bicarbonate 24.1 (22.5–25.5) mEq/L and K 3.8 (3.5–4.1) mEq/L. Conclusion IHD for critically ill patients with cancer and AKI offered acceptable hemodynamic stability and provided adequate metabolic control. PMID:26938932

  15. Mesoscopic modeling of cancer photothermal therapy using single-walled carbon nanotubes and near infrared radiation: insights through an off-lattice Monte Carlo approach.

    PubMed

    Gong, Feng; Hongyan, Zhang; Papavassiliou, Dimitrios V; Bui, Khoa; Lim, Christina; Duong, Hai M

    2014-05-23

    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.

  16. Single skip metastasis in sentinel lymph node: In an early gastric cancer.

    PubMed

    Bara, Tivadar; Gurzu, Simona; Jung, Ioan; Kadar, Zoltan; Sugimura, Haruhiko; Bara, Tivadar

    2015-09-01

    Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer (GC). Although there is a practical approach to the intraoperative detection of sentinel lymph nodes (SLNs), such a procedure is not included in the European surgical protocol. In this report, we present a practical approach to SLN mapping in a representative case with early gastric cancer (EGC). A 74-year-old female was hospitalized with an endoscopically observed, superficially ulcerated tumor located in the antral region. Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer. An incidentally detected blue-stained lymph node located along the middle colic artery was also removed. This was detected 40 min after injection of the methylene blue. Histopathologic examination showed a pT1b-staged well-differentiated HER-2-negative adenocarcinoma. All of the 41 LNs located at the first, third, and fifth station of the regional LN compartments were found to be free of tumor cells. The only lymph node with metastasis was located along the middle colic artery and was considered a non-regional lymph node. This incidentally identified skip metastasis indicated stage IV GC. A classic chemotherapy regimen was given, and no recurrences were observed six months after surgery. In this representative case, low-cost SLN mapping, with a longer intraoperative waiting time, totally changed the stage of the tumor in a patient with EGC.

  17. Incidence of nonmelanoma skin cancer after human organ transplantation: single-center experience in Hungary.

    PubMed

    Fekecs, T; Kádár, Z; Battyáni, Z; Kalmár-Nagy, K; Szakály, P; Horváth, O P; Wéber, G; Ferencz, A

    2010-01-01

    There is increasing evidence that nonmelanoma skin cancers (NMSCs) are the most frequently observed tumors in transplant recipients. The incidence of posttransplantation NMSC was determined using our dermatologic screening program. Included in the study were 116 white adults (70 men and 46 women; median age, 49.3 years) who had undergone kidney or combined kidney-pancreas transplantation, with follow-up from September 2008 to December 2009. All patients underwent a full skin examination for NMSC, and completed a standardized questionnaire. Screening resulted in detection of 16 NMSCs in 11 patients out of 116 (9.5%). Lesions were equally distributed by sex, and were detected at a median of 4.1 years posttransplantation. Histologic analysis verified 13 basal cell carcinomas and 3 squamous cell carcinomas (ratio, 4:1). The incidence of NMSC was significantly greater in patients who received cyclosporine immunosuppression therapy (16 vs 1; P < .05), had experienced 2 or more painful sunburns before transplantation (10 vs 11), or worked outdoors (10 vs 11). These data indicate the relevance of skin cancer surveillance in transplant recipients. Our results correspond to international statistics except for the ratio of basal cell carcinoma to squamous cell carcinoma. Further studies are needed to elucidate the reasons for this difference.

  18. How to improve walking, balance and social participation following stroke: a comparison of the long term effects of two walking aids--canes and an orthosis TheraTogs--on the recovery of gait following acute stroke. A study protocol for a multi-centre, single blind, randomised control trial

    PubMed Central

    2012-01-01

    Background Annually, some 9000 people in Switzerland suffer a first time stroke. Of these 60% are left with moderate to severe walking disability. Evidence shows that rehabilitation techniques which emphasise activity of the hemiplegic side increase ipsilesional cortical plasticity and improve functional outcomes. Canes are commonly used in gait rehabilitation although they significantly reduce hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset with elasticated strapping) significantly increases hemiplegic muscle activity during gait. The aim of the present study is to investigate the long term effects on the recovery of gait, balance and social participation of gait rehabilitation with TheraTogs compared to gait rehabilitation with a cane following first time acute stroke. Methods/Design Multi-centre, single blind, randomised trial with 120 patients after first stroke. When subjects have reached Functional Ambulation Category 3 they will be randomly allocated into TheraTogs or cane group. TheraTogs will be applied to support hip extensor and abductor musculature according to a standardised procedure. Cane walking held at the level of the radial styloid of the sound wrist. Subjects will walk throughout the day with only the assigned walking aid. Standard therapy treatments and usual care will remain unchanged and documented. The intervention will continue for five weeks or until patients have reached Functional Ambulation category 5. Outcome measures will be assessed the day before begin of intervention, the day after completion, 3 months, 6 months and 2 years. Primary outcome: Timed "up and go" test, secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius, activation patterns of hemiplegic leg musculature, temporo-spatial gait parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic balance, daily activity measured by accelerometry, Stroke Impact Scale. Significance levels will be 5% with 95

  19. Association Between Single Nucleotide Polymorphisms in DNA Polymerase Kappa Gene and Breast Cancer Risk in Chinese Han Population

    PubMed Central

    Dai, Zhi-Jun; Liu, Xing-Han; Ma, Yun-Feng; Kang, Hua-Feng; Jin, Tian-Bo; Dai, Zhi-Ming; Guan, Hai-Tao; Wang, Meng; Liu, Kang; Dai, Cong; Yang, Xue-Wen; Wang, Xi-Jing

    2016-01-01

    Abstract DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk. We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses. We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC. Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women. PMID:26765445

  20. Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes.

    PubMed

    Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo; Zheng, Lixia

    2016-11-01

    A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. PMID:27524057

  1. Femto-molar detection of cancer marker-protein based on immuno-nanoplasmonics at single-nanoparticle scale

    NASA Astrophysics Data System (ADS)

    Hong, Yoochan; Lee, Eugene; Ku, Minhee; Suh, Jin-Suck; Yoon, Dae Sung; Yang, Jaemoon

    2016-05-01

    We describe an in vitro biomarker sensor based on immuno-silver nanomarbles (iSNMs) and the nanoscattering spectrum imaging analysis system using localized surface plasmon resonance (LSPR). In particular, highly monodisperse SNMs with large figures of merit are prepared, and the sensing substrates are also fabricated using the nanoparticle adsorption method. The high sensitivity of the LSPR sensor based on an SNM is confirmed using various solvents that have different refractive indexes. For the sensitive and specific detection of epithelial cell adhesion molecules (EpCAMs) expressed on cancer cells, the surface of the SNM is conjugated with an anti-EpCAM aptamer, and molecular sensing for the EpCAM expression level is carried out using whole cell lysates from various cancer cell lines. Collectively, we have developed a biomarker-detectable LSPR sensor based on iSNMs, which allows for the sensitive and effective detection of EpCAMs at both the single-cell and femto-molar level.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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 and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic ‘roadmap’ that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity.

  7. SERS assay of telomerase activity at single-cell level and colon cancer tissues via quadratic signal amplification.

    PubMed

    Shi, Muling; Zheng, Jing; Liu, Changhui; Tan, Guixiang; Qing, Zhihe; Yang, Sheng; Yang, Jinfeng; Tan, Yongjun; Yang, Ronghua

    2016-03-15

    As an important biomarker and therapeutic target, telomerase has attracted extensive attention concerning its detection and monitoring. Recently, enzyme-assisted amplification approaches have provided useful platforms for the telomerase activity detection, however, further improvement in sensitivity is still hindered by the single-step signal amplification. Herein, we develop a quadratic signal amplification strategy for ultrasensitive surface-enhanced Raman scattering (SERS) detection of telomerase activity. The central idea of our design is using telomerase-induced silver nanoparticles (AgNPs) assembly and silver ions (Ag(+))-mediated cascade amplification. In our approach, each telomerase-aided DNA sequence extension could trigger the formation of a long double-stranded DNA (dsDNA), making numerous AgNPs assembling along with this long strand through specific Ag-S bond, to form a primary amplification element. For secondary amplification, each conjugated AgNP was dissolved into Ag(+), which can effectively induce the 4-aminobenzenethiol (4-ABT) modified gold nanoparticles (AuNPs@4-ABT) to undergo aggregation to form numerous "hot-spots". Through quadratic amplifications, a limit of detection down to single HeLa cell was achieved. More importantly, this method demonstrated good performance when applied to tissues from colon cancer patients, which exhibits great potential in the practical application of telomerase-based cancer diagnosis in early stages. To demonstrate the potential in screening the telomerase inhibitors and telomerase-targeted drugs, the proposed design is successfully employed to measure the inhibition of telomerase activity by 3'-azido-3'-deoxythymidine.

  8. A 3.5-cm Single-Incision VATS Anatomical Segmentectomy for Lung Cancer

    PubMed Central

    Igai, Hitoshi; Ibe, Takashi; Kawatani, Natsuko; Shimizu, Kimihiro; Takeyoshi, Izumi

    2014-01-01

    The results of several pulmonary resections using a uniportal approach have been published. However, there are no reports of uniportal thoracoscopic anatomic segmentectomy in Japan. We have a fundamental belief in “reduced-port surgery” and therefore routinely perform uniportal thoracoscopic surgery for patients with pneumothorax. This report describes a successful case of uniportal thoracoscopic anatomic segmentectomy through a 3.5-cm incision in a 76-year-old woman with primary lung cancer. The patient was pathologically diagnosed with multiple primary adenocarcinomas stage IA (T1aN0M0). Postoperatively, no analgesics were needed. The operative procedure is described in detail and includes technical tips such as the pulley method, extra-vessel exposure, the shaft-on-shaft technique, one-hand encircling, and one-hand exposure. The selection criteria for uniportal thoracoscopic segmentectomy limit its use. PMID:25224514

  9. Adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Stell, P. M.; Rawson, N. S.

    1990-01-01

    An overview is presented of 23 trials of adjuvant chemotherapy in squamous cell carcinoma of the head and neck. These were reviewed from the point of view of design of the trial, analysis of survival, response rates, meta-analysis, site of failure, toxicity and cost. The minimal increase in survival that could be detected ranged from 11 to 51%, with a median of 25%. No trial was big enough to detect the likely increase of survival, which is 5%. Many trials excluded some eligible patients before randomisation, the proportion being 21% in those series with details. A further 9% of treated patients were excluded from analysis. A response rate in four induction studies of 47% equated with a 6% increase in cancer mortality. Meta-analysis showed an insignificant overall improvement in cancer mortality of 0.5%. Induction chemotherapy, synchronous chemotherapy and induction/maintenance chemotherapy did not affect cancer mortality whereas synchronous/maintenance therapy did. Cisplatinum, methotrexate, bleomycin, 5-FU and a variety of other regimens did not affect the death rate from cancer, but the combination of VBM significantly increased it. Neither single agent nor combination chemotherapy produced a significant reduction of cancer deaths. The rate of locoregional failure was significantly lower in the treated arms, whereas the metastatic rate was similar in both arms. Only three papers gave full details of toxicity with grading: these showed a high toxicity rate. The mortality rate from chemotherapy in nine series averaged 6.5%. PMID:2140045

  10. Regional lymph node radiotherapy in breast cancer: single anterior supraclavicular field vs. two anterior and posterior opposed supraclavicular fields

    PubMed Central

    Houshyari, Mohammad; Kashi, Amir Shahram Yousefi; Varaki, Sakineh Soleimani; Rakhsha, Afshin; Blookat, Eftekhar Rajab

    2015-01-01

    Background: The treatment of lymph nodes engaged in breast cancer with radiotherapy leads to improved locoregional control and enhanced survival rates in patients after surgery. The aim of this study was to compare two treatment techniques, namely single anterior posterior (AP) supraclavicular field with plan depth and two anterior and posterior opposed (AP/PA) supraclavicular fields. In the study, we also examined the relationships between the depth of supraclavicular lymph nodes (SCLNs) and the diameter of the wall of the chest and body mass index (BMI). Methods: Forty patients with breast cancer were analyzed using computed tomography (CT) scans. In planning target volume (PTV), the SCLNs and axillary lymph nodes (AXLNs) were contoured, and, with the attention to PTV, supraclavicular (SC) depth was measured. The dosage that reached the aforementioned lymph nodes and the level of hot spots were investigated using two treatment methods, i.e., 1) AP/PA and 2) AP with three-dimensional (3D) planning. Each of these methods was analyzed using the program Isogray for the 6 MV compact accelerator, and the diameter of the wall of the chest was measured using the CT scan at the center of the SC field. Results: Placing the plan such that 95% of the target volume with 95% or greater of the prescribed dose of 50 Gy (V95) had ≥95% concordance in both treatment techniques. According to the PTV, the depth of SCLNs and the diameter of the wall of the chest were 3–7 and 12–21cm, respectively. Regression analysis showed that the mean SC depth (the mean Plan depth) and the mean diameter of the wall of the chest were related directly to BMI (p<0.0001, adjusted R2=0.67) and (p<0.0001, adjusted R2=0.71), respectively. Conclusion: The AP/PA treatment technique was a more suitable choice of treatment than the AP field, especially for overweight and obese breast cancer patients. However, in the AP/PA technique, the use of a single-photon, low energy (6 MV) caused more hot spots

  11. Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer.

    PubMed

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y; Li, Chun

    2015-07-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[(64)Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[(64)Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC.

  12. Single Agent Nanoparticle for Radiotherapy and Radio-Photothermal Therapy in Anaplastic Thyroid Cancer

    PubMed Central

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y.; Li, Chun

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. PMID:25913249

  13. Development and Testing of a Single Frequency Terahertz Imaging System for Breast Cancer Detection

    PubMed Central

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

    2013-01-01

    The ability to discern malignant from benign tissue in excised human breast specimens in Breast Conservation Surgery (BCS) was evaluated using 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. The system design and characterization is 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. PMID:25055306

  14. Efficacy of concurrent single-agent chemotherapy using radiotherapy in patients with cervical cancer: a meta-analysis.

    PubMed

    Zhang, Ying; Yang, Zhicheng; Zhou, Yijin; Pan, Jingjing; Liu, Yongyuan

    2015-01-01

    Concurrent chemoradiotherapy has proven to be more effective on patients with advanced cervical cancer than radiotherapy alone. Although cisplatin has been recommended to be the standard agent in chemotherapy, it has some limitations in clinical use because of its strong side effects. Moreover, the optimal chemotherapy regimen remains unclear. A comprehensive electronic search was conducted via the Internet retrieval system to identify eligible trials. The ending points included response, overall survival (OS), local recurrent, and distant metastasis rates. Odds ratios and 95% confidence interval were calculated to compare the effects. Fifteen trials with 1142 patients were eligible. With regard to the response rate, only nedaplatin showed a significant improvement compared with cisplatin. Docetaxel, pacitaxel, fluoropyrimidine, paclitaxel liposome, and irinotecan did not show any advantages. When targeted on OS or local recurrent rate, no significant advantage was found when these single-drug regimens were compared with cisplatin. However, when aimed at distant metastasis rate, fluoropyrimidine showed a disadvantage to cisplatin, whereas others showed equal efficacy. Nedaplatin, docetaxel, pacitaxel, and fluoropyrimidine showed a better effect on reducing chemotherapy toxicity than cisplatin. Single-drug chemotherapy concurrent with radiotherapy, except for nedaplatin, may have no advantage on clinical outcomes when compared with cisplatin but showed a better effect on reducing chemotherapy toxicity, which could be used as an alternative to patients who can not tolerate the side effects of cisplatin. Nedaplatin is also effective and safe, and may be highly valuable in clinical applications. PMID:26309518

  15. Towards intrinsic graphene biosensor: A label-free, suspended single crystalline graphene sensor for multiplex lung cancer tumor markers detection.

    PubMed

    Li, Peng; Zhang, Bo; Cui, Tianhong

    2015-10-15

    Graphene biosensors reported so far are based on polycrystalline graphene flakes which are anchored on supporting substrates. The influence of grain boundary and the scattering from substrate drastically degrade the properties of graphene and conceal the performance of intrinsic graphene as a sensor. Here we report a label-free biosensor based on suspended single crystalline graphene (SCG), which can get rid of grain boundary and substrate scattering, revealing the biosensing mechanism of intrinsic graphene for the first time. Monolayer SCG flakes were derived from low pressure chemical vapor deposition (LPCVD) method. Multiplex detection of three different lung cancer tumor markers was realized. The suspended structure can largely improve the sensitivity and detection limit (0.1 pg/ml) of the sensor, and the single crystalline nature of SCG enable the biosensor to have superior uniformity compared to polycrystalline ones. The SCG sensors exhibit superb specificity and large linear detection range from 1 pg/ml to 1 μg/ml, showing the prominent advantages of graphene as a sensing material.