Pregnancy and perinatology ; research programs of the National Institute of Child Health and Human Development /

Cover title.

Proceedings of the Third Japan-U.S. Seminar on HTGR Safety Technology, June 2-3, 1982, Brookhaven National Laboratory, Upton, New York 11973 /

Includes bibliographical references.

Manual of procedures /

"Revised April 1979."

Breast cancer teams:the impact of constitution, new cancer workload and methods of operation on their effectiveness

National guidance and clinical guidelines recommended multidisciplinary teams (MDTs) for cancer services in order to bring specialists in relevant disciplines together, ensure clinical decisions are fully informed, and to coordinate care effectively. However, the effectiveness of cancer teams was not previously evaluated systematically. A random sample of 72 breast cancer teams in England was studied (548 members in six core disciplines), stratified by region and caseload. Information about team constitution, processes, effectiveness, clinical performance, and members' mental well-being was gathered using appropriate instruments. Two input variables, team workload (P=0.009) and the proportion of breast care nurses (P=0.003), positively predicted overall clinical performance in multivariate analysis using a two-stage regression model. There were significant correlations between individual team inputs, team composition variables, and clinical performance. Some disciplines consistently perceived their team's effectiveness differently from the mean. Teams with shared leadership of their clinical decision-making were most effective. The mental well-being of team members appeared significantly better than in previous studies of cancer clinicians, the NHS, and the general population. This study established that team composition, working methods, and workloads are related to measures of effectiveness, including the quality of clinical care. © 2003 Cancer Research UK.

The application of aryne chemistry and use of α-diazo carbonyl derivatives in indazole synthesis with biological evaluation

This thesis outlines the synthetic chemistry involved in the preparation of a range of novel indazole compounds and details the subsequent investigation into their potential as biologically active agents. The synthetic route utilised in this research to form the indazole structure was the [3+2] dipolar cycloaddition of diazo carbonyl compounds with reactive aryne intermediates generated in situ. The preparation of further novel indazole derivatives containing different functional groups and substituents was performed by synthesising alternative 1,3- dipole and dipolarophile analogues and provided additionally diverse compounds. Further derivatisation of the indazole product was made possible by deacylation and alkylation methods. Transformation reactions were performed on alkenecontaining ester side chains to provide novel epoxide, aldehyde and tertiary amine derivatives. The first chapter is a review of the literature beginning with a short overview on the structure, reactivity and common synthetic routes to diazo carbonyl derivatives. More attention is given to the use of diazo compounds as 1,3-dipoles in cycloaddition reactions or where the diazo group is incorporated into the final product. A review of the interesting background, structure and reactivity of aryne intermediates is also presented. In addition, some common syntheses of indazole compounds are presented as well as a brief discussion on the importance of indazole compounds as therapeutic agents. The second chapter discusses the synthetic routes employed towards the synthesis of the range of indazoles. Initially, the syntheses of the diazo carbonyl and aryne precursors are described. Next, the synthetic methods to prepare the indazole compounds are provided followed by discussion on derivatisation of the indazole compounds including N-deacylation, N-benzylation and ester side-chain transformation of some alkene-containing indazoles. A series of novel indazole derivatives were submitted for anti-cancer screening at the U.S National Cancer Institute (NCI). A number of these derivatives were identified as hit compounds, with excellent growth inhibition. The results obtained from biological evaluation from the NCI are provided with further results pending from the Community for Open Antimicrobial Drug Discovery. The third chapter details the full experimental procedures, including spectroscopic and analytical data for all the compounds prepared during this research.

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747)

OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC).

PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves.

RESULTS: The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively.

CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.

National Cancer Strategy 2006: a Strategy for Cancer Control in Ireland – Evaluation Panel Report

Review of ‘A Strategy for Cancer Control in Ireland’. The review was led by Professor Pádraig Warde of the Princess Margaret Cancer Centre, Toronto.  The evaluation panel was very impressed with the excellent progress in the cancer control system in Ireland since the publication of “A Strategy for Cancer Control in Ireland” in 2006.   Download the report here.

Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009

Background: Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009. Methods: National data on incident oral cancers [ICD 10 codes C01-C06] were obtained from the National Cancer Registry Ireland from 1994 to 2009. We estimated annual percentage change (APC) in oral cancer incidence during 1994–2009 using joinpoint regression software (version 4.2.0.2). The lifetime risk of oral cancer to age 79 was estimated using Irish incidence and population data from 2007 to 2009. Survival rates were also examined using Kaplan-Meier curves and Cox proportional hazard models to explore the influence of several demographic/lifestyle covariates with follow-up to end 2012. Results: Data were obtained on 2,147 oral cancer incident cases. Men accounted for two-thirds of oral cancer cases (n = 1,430). Annual rates in men decreased significantly during 1994–2001 (APC = -4.8 %, 95 % CI: −8.7 to −0.7) and then increased moderately (APC = 2.3 %, 95 % CI: −0.9 to 5.6). In contrast, annual incidence increased significantly in women throughout the study period (APC = 3.2 %, 95 % CI: 1.9 to 4.6). There was an elevated risk of death among oral cancer patients who were: older than 60 years of age; smokers; unemployed or retired; those living in the most deprived areas; and those whose tumour was sited in the base of the tongue. Being married and diagnosed in more recent years were associated with reduced risk of death. Conclusion: Oral cancer increased significantly in both sexes between 1999 and 2009 in Ireland. Our analyses demonstrate the influence of measured factors such as smoking, time of diagnosis and age on observed trends. Unmeasured factors such as alcohol use, HPV and dietary factors may also be contributing to increased trends. Several of these are modifiable risk factors which are crucial for informing public health policies, and thus more research is needed.

Diet and cancer in Northeast Brazil: evaluation of eating habits and food group consumption in relation to breast cancer

Realizou-se um estudo do tipo caso-controle de base hospitalar no Município de João Pessoa, Paraíba, Brasil. Participaram 183 indivíduos (89 casos e 94 controles) na faixa etária entre 30 e 80 anos, com pareamento por idade. O consumo alimentar de casos e controles foi avaliado por alimentos e grupos de alimentos categorizados em tercis de consumo. A estimativa dos valores da odds ratio (OR) e intervalos de confiança de 95% (IC95%) foi realizada por regressão logística múltipla não-condicional. O consumo de frutas e sucos, feijão e leite e derivados apresentou uma forte associação com a redução no risco de câncer de mama. O consumo de carnes vermelhas e de carnes fritas esteve positivamente associado ao risco de câncer de mama (carne vermelha - OR = 4.30; IC95%: 1,74-10,67; p = 0,00). Não foi observada associação entre o consumo dos grupos de vegetais e embutidos com o câncer de mama. Carne vermelha e carnes fritas podem ser fatores de risco, e o consumo de frutas, feijão e leite e derivados pode atuar como protetor do câncer de mama

Cancer knowledge and skills of interns in Australia and New Zealand in 2001: comparison with 1990, and between course types

Objective: To compare the cancer knowledge and skills of interns in 2001 who graduated from graduate medical program (GMP) courses with those from non-GMP courses, and to compare the cancer knowledge and skills of interns in 2001 with those who completed a similar survey in 1990. Design: Questionnaire survey of recently graduated interns in a random sample of Australian and New Zealand hospitals. The questionnaire was designed to allow direct comparison with the 1990 survey, and was guided by the Australian Cancer Society's Ideal Oncology Curriculum for Medical Schools. Results: 443 interns completed the survey (response rate, 62%; 42 were excluded, leaving 401 surveys for analysis: 118 from GMP courses and 283 from non-GMP courses). Interns from GMP courses felt more competent than those from non-GMP courses at discussing death (P= 0.02), breaking bad news (P= 0.04) and advising on smoking cessation (P= 0.02), but less competent at preparing a patient for a hazardous procedure (P= 0.02). Mote GMP interns would refer a breast cancer patient to a multidisciplinary clinic (83% versus 70%; P= 0.03). Knowledge about cancer risks and prognosis was significantly less in GMP interns, but GMP interns rated their clinical skills, such as taking a Pap smear, higher than non-GMP interns. The GMP and non-GMP groups did not differ in their exposure to cancer patients, but compared with 1990 interns recent graduates had less exposure to patients with cancer. Conclusions: GMP curricula appear to have successfully introduced new course material and new methods of teaching, but have not always succeeded in producing doctors with better knowledge about cancer. Recent graduates have less exposure to cancer patients than those who trained 10 years ago.

Efficacy of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy,, depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive. HTV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). Conclusion: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.