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Biomedical subjects

D W Nixon

Publications and source records attributed to D W Nixon.

At least 19 recordsLinked to original sources
PubMed1999

p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells.

Ellagic acid is a phenolic compound present in fruits and nuts including raspberries, strawberries and walnuts. It is known to inhibit certain carcinogen-induced cancers and may have other chemopreventive properties. The effects of ellagic acid on cell cycle events and apoptosis were studied in cervical carcinoma (CaSki) cells. We found that ellagic acid at a concentration of 10(-5) M induced G arrest within 48 h, inhibited overall cell growth and induced apoptosis in CaSki cells after 72 h of treatment. Activation of the cdk inhibitory protein p21 by ellagic acid suggests a role for ellagic acid in cell cycle regulation of cancer cells.

Apoptosis↗
PubMed1998

Volunteers as adjunct researchers in a cancer prevention trial: the American Cancer Society Colon Polyp Prevention Study.

BACKGROUND: In April 1991, the Virginia Division of the American Cancer Society (ACS) initiated the feasibility phase of the Colon Polyp Prevention Study (CPPS) to determine whether a high fiber supplement would decrease new adenomatous colorectal polyp occurrence. The feasibility phase had two specific objectives: 1) to evaluate accrual and compliance to the designed protocol and 2) to evaluate and demonstrate the effectiveness of volunteers as research assistants. The CPPS is an innovative project in which trained volunteers play a significant role in the research process. METHODS: In the CPPS, volunteer adjunct researchers (VARs) were trained to perform individual dietary data collection and intervention and other general study monitoring functions. VARs were trained, certified, and monitored in the performance of their assigned tasks by ACS staff and expert consultants. RESULTS: A total of 119 volunteers were trained as VARs, 74 of whom were certified and matched to a study participant. Between 1991-1995, only six VARs left the study. After active accrual of participants to the study ceased in 1995, 38 VARs (50% of the certified VARs) continued to monitor the active study participants. All VARs were consistently able to conduct the functions for which they were trained. CONCLUSIONS: In spite of expected volunteer attrition rates, a core of 38 dedicated VARs were matched to 72 participants and demonstrated the ability to perform selected data collecting activities on a consistent and efficient basis. The use of trained volunteers has allowed the CPPS to function in its feasibility phase at personnel cost considerably less than that of other similar cancer prevention trials.

American Cancer Society↗
PubMed1998

The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells.

Retinoids, including natural vitamin A and its analogs, have been closely studied as chemopreventive drugs. The mechanism of action of retinoids, however, is not completely understood. Our study evaluated the effects of all-trans (high affinity ligand for both RAR and RXR receptors) and 9-cis retinoic acid (binds only with RXR receptors) on E6-E7 transcription, cell proliferation, cell cycle distribution, and p53 expression in CaSki cells, a cell line derived from cervical carcinoma containing 600 copies of the HPV-16 genome. Using quantitative RT-PCR analysis, we found that CaSki cells treated with all trans retinoic acid (ATRA) for seven days had a remarkably low level of E6-E7 transcription at 10(-5) M to 10(-9) M concentrations. A smaller inhibitory effect was observed on the E6-E7 transcription at a concentration of 10(-5) M with only 9-cis retinoic acid. Flow cytometric analysis revealed that cells treated with both all trans and 9-cis RA showed an increase in the mean percentage (93.5% and 86.1% respectively) of cells in the G1 phase as compared to untreated CaSki cells (55%) and normal keratinocytes (58%). The percentage of cells in the S phase decreased from a mean percentage of 28 and 26.5 to 5.8 and 5, respectively, after treatment with all trans retinoic acid and 9-cis retinoic acid. An increase in the level of immunophenotypic expression of wild type p53 was also noted after treatment with all trans retinoic acid and 9-cis retinoic acid. All trans and 9-cis retinoic acid may act on highly proliferating tumor cells by initially arresting DNA synthesis and inducing G1 arrest. In addition, they may be inducing a p53 dependent cell cycle arrest and thus suggests that all-trans and 9-cis retinoic acid may have a cytostatic effect rather than a cytotoxic effect on CaSki cells. The increased expression of p53 positive cells and the inhibition of E6/E7 transcription after treatment with these retinoids may indicate the potential role of all trans and 9-cis retinoic acid as a cell cycle regulator and an antiviral chemoprevention agent.

Alitretinoin↗
PubMed1997

Feasibility of using volunteer research staff to deliver and evaluate a low-fat dietary intervention: the American Cancer Society Breast Cancer Dietary Intervention Project.

This report presents the results of a study to examine the feasibility of using volunteers as research staff for a randomized trial of whether reduction in dietary fat intake could prevent or delay breast cancer recurrence. We examined whether volunteers could be trained to recruit study participants, deliver a complex and intensive dietary intervention, and monitor intervention effectiveness. Volunteers, who were mostly employed nurses and dietitians, screened 521 women, of whom 293 were eligible and 144 were randomized. Participants were postmenopausal women under age 75, who had recently been diagnosed with breast cancer and treated with either mastectomy or lumpectomy. At 1 year postrandomization, 77% of intervention and 75% of control participants remained active in the study. Intervention effects (change in intervention group minus change in control group) at 3, 6, and 12 months postrandomization were 5.9, 8.4, and 7.2% energy from fat and 1.7, 3.0, and 3.5 kg body weight (all P < 0.001). These results were similar to those from other studies that used paid, professional staff to deliver and monitor interventions. Results from this feasibility study suggest that volunteer-based health organizations can provide research opportunities for health practitioners and can conduct high-quality research at lower costs.

Adult↗
PubMed1996

Cancer, cancer cachexia, and diet: lessons from clinical research.

Cachexia is a common cause of morbidity and mortality in cancer patients. Successful nutritional repletion might enhance treatment results, quality of life, and survival. In the past, attempts at nonvolitional feeding (enteral and parenteral techniques) have not been as successful as initially hoped. The cachectic cancer patient's loss of lean body mass has been very difficult to restore, although fat can be repleted. Laboratory and epidemiologic investigations have suggested that dietary calories and dietary fat may play a promotional role in cancer. Overfed animals and obese humans both have an increased tendency for development of malignancy. Breast cancer has been investigated extensively for its relationship to diet. Certain fatty acids appear to stimulate breast cancer, as do obesity-related changes in circulating hormones. Obesity in breast cancer and weight gain on adjuvant therapy may therefore be adverse prognostic signs. Clinical trials of decreasing dietary fat as an adjuvant to breast cancer therapy are in progress. The current challenge in nutritional management of the cancer patient is to incorporate laboratory, epidemiologic, and clinical data into a successful repletion strategy. It seems unlikely that traditional methods of supplying excess calories will succeed, so that other, more specific nutritional manipulations should be evaluated in clinical trials.

Animals↗
PubMed1994

Special aspects of cancer prevention trials.

The results of early cancer prevention trials now are being reported, and new trials have begun or are being designed. Initial trials used agents such as vitamins and minerals, generally regarded as safe. The trials in progress are using similar agents or macronutrient manipulation, but some have incorporated drugs with low but definite toxic potential, such as tamoxifen. Appropriate prevention trial design requires careful consideration of agent toxicity and the use of such agents in healthy individuals. Full disclosure of risks and benefits to potential subjects is necessary. Other considerations are study duration (usually very long) and subject number (usually very large), both of which increase the cost of a trial. Successful prevention trials must overcome these barriers through innovative design. Possible innovations include the use of intermediate marker end-points, the enrollment of subjects at high risk for a specific cancer, and the use of volunteers to help conduct trials.

Breast Neoplasms↗
PubMed1991

Cancer prevention clinical trials.

If external factors other than tobacco (e.g., diet, sunlight) are responsible in a major way for some cancers, then appropriate manipulation and alteration of such factors should decrease the rate of these cancers. Clinical trials in cancer prevention are an attempt to test this approach. Prevention trials are based on knowledge gained from the laboratory and from epidemiology, and they are the only way to conclusively demonstrate the effectiveness of a given prevention intervention in humans. This article discusses the development of prevention trials and specific current and future trials.

Clinical Trials as Topic↗
PubMed1990

Adjuvant systemic therapy.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Concepts in cancer chemoprevention research.

Cancer prevention through the use of chemical intervention regimens (chemoprevention) is an emerging field with broad potential for impacting on cancer incidence rates in defined high-risk groups and the general population. Information from cancer epidemiologic studies coupled with that from basic research on cancer biology have combined to reveal several categories of agents with potential for clinical application, including natural and synthetic tumor suppressive retinoids and antioxidants. Chemopreventive agents may inhibit the development of cancer by limiting exposure to initiators or promoters through stimulation of inactivation or excretion mechanisms. Biological consequences of exposure to carcinogens may also be interfered with, e.g., by inhibiting the activation of proto-oncogenes or by antagonizing the effects of oncogene expression. Hundreds of compounds with chemopreventive efficacy in vitro have been isolated from foods and plant products. The testing and development of candidate chemopreventives proceeds through a series of preclinical efficacy screens, followed by controlled clinical trials.

Animals↗
PubMed1990

Garlic: a review of its relationship to malignant disease.

Garlic (Allium sativum) has had an important dietary and medicinal role for centuries. It is now known that garlic contains chemical constituents with antibiotic, lipid-lowering, detoxification, and other medicinal effects in the body. This article reviews some of the physiological characteristics of garlic and examines the relationship between garlic and cancer prevention and treatment. Hypotheses regarding the possible role of garlic in modulating mechanisms that may alter the carcinogenic process are discussed.

Animals↗
PubMed1990

The effect of early caloric restriction on colonic cellular growth in rats.

Although the inhibitory effect of caloric restriction on tumorigenesis is substantial and well known, the pertinent mechanisms remain to be determined. We recently suggested that the risk of cancer may be directly related to the total number of dividing cells within an affected organ. This study evaluates the effects of early caloric restriction on the cellular growth of the colon. The experiment began one day postpartum and ended six weeks later with the killing of all animals. It consisted of two consecutive periods: a) three weeks of suckling and b) three weeks postweaning. Animals whose food was restricted only during the suckling period showed normal colons when killed at six weeks. Caloric restriction (40%) for three weeks postweaning resulted in colons of lower weight with fewer cells (less total DNA) and reduced total DNA synthesis [( 3H]thymidine uptake, dpm/colon) when compared with animals fed ad libitum postweaning. Conversely, only rats fed ad libitum from birth through the first three weeks after weaning demonstrated an increase (21%) in the rate of DNA synthesis (dpm/mg DNA) compared with other animals. In addition, the colonic crypts showed no differences in the number of cells or the number of dividing cells, as determined by autoradiography. By contrast, the total number of crypts (and/or the number of mucosal cells between crypts) are reduced, and hence the total number of colonic mucosal cells dividing at any given time are similarly decreased. The reduced number of dividing cells in the colons of these animals (i.e., those restricted postweaning) could explain previous data suggesting that they are resistant to the induction of colon cancer.

Animals↗