Anti-tumour activity in vitro and in vivo of selective differentiating agents containing hydroxamate

A series of hydroxamates, which are not metalloprotease inhibitors, have been found to be selectively toxic to a range of transformed and human tumour cells without killing normal cells (fibroblasts, melanocytes) at the same concentrations. Within 24 h of treatment, drug action is characterized by morphological reversion of tumour cells to a more normal phenotype (dendritic morphology), and rapid and reversible acetylation of histone H4 in both tumour and normal cells. Two; hydroxamates inhibited growth of xenografts of human melanoma cells in nude mice; resistance did not develop in vivo or in vitro. A third hydroxamate, trichostatin A, was active in vitro but became inactivated and had no anti-tumour activity in vivo. Development of dendritic morphology was found to be dependent upon phosphatase activity, RNA and protein synthesis. Proliferating hybrid clones of sensitive and resistant cells remained sensitive to ABHA, indicating a dominant-negative mechanism of sensitivity. Histone H4 hyperacetylation suggests that these agents act at the chromatin level. This work may lead to new drugs that are potent, and selective anti-tumour agents with low toxicity to normal Cells

Risk prediction tools for cancer in primary care.

Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/bjc.2015.40

Screening Patients with a Family History of Colorectal Cancer

OBJECTIVES: To compare screening practices and beliefs in patients with and without a clinically important family history. DESIGN: We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history. PARTICIPANTS: One thousand eight hundred seventy of 6,807 randomly selected patients ages 35–55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years. MEASUREMENTS: Recognition of increased risk, screening practices, and beliefs—all according to strength of family history and patient’s age. RESULTS: Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history. CONCLUSIONS: More efforts are needed to translate information about family history of colorectal cancer into the care of patients

Aid-Assisted Decision-Making and Colorectal Cancer Screening: A Randomized Controlled Trial

Shared decision-making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results

Colorectal cancer risk assessment and screening recommendation: a community survey of healthcare providers' practice from a patient perspective

<p>Abstract</p> <p>Background</p> <p>Family history is a common risk factor for colorectal cancer (CRC), yet it is often underused to guide risk assessment and the provision of risk-appropriate CRC screening recommendation. The aim of this study was to identify from a patient perspective health care providers' current practice relating to: (i) assessment of family history of CRC; (ii) notification of "increased risk" to patients at "moderately/potentially high" familial risk; and (iii) recommendation that patients undertake CRC screening.</p> <p>Methods</p> <p>1592 persons aged 56-88 years randomly selected from the Hunter Community Study (HCS), New South Wales, Australia were mailed a questionnaire. 1117 participants (70%) returned a questionnaire.</p> <p>Results</p> <p>Thirty eight percent of respondents reported ever being asked about their family history of CRC. Ever discussing family history of CRC with a health care provider was significantly more likely to occur for persons with a higher level of education, who had ever received screening advice and with a lower physical component summary score. Fifty one percent of persons at "moderately/potentially high risk" were notified of their "increased risk" of developing CRC. Thirty one percent of persons across each level of risk had ever received CRC screening advice from a health care provider. Screening advice provision was significantly more likely to occur for persons who had ever discussed their family history of CRC with a health care provider and who were at "moderately/potentially high risk".</p> <p>Conclusions</p> <p>Effective interventions that integrate both the assessment and notification of familial risk of CRC to the wider population are needed. Systematic and cost-effective mechanisms that facilitate family history collection, risk assessment and provision of screening advice within the primary health care setting are required.</p