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At least 19 recordsLinked to original sources
PubMed1998

Phase III, large-scale chemoprevention trials. Approach to chemoprevention clinical trials and phase III clinical trial of tamoxifen as a chemopreventive for breast cancer--the US National Cancer Institute experience.

Clinical trials to evaluate interventions for cancer prevention are designed as early (phase I, IIa, and IIb) or late-phase studies. Whereas the former are small and generally rely on intermediate endpoint biomarkers of carcinogenesis, the latter are large-scale, long-term, randomized, phase III studies that address endpoints such as cancer incidence. The Breast Cancer Prevention Trial, P-1, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), is discussed as an example of a large, extended, phase III trial designed to answer the question of whether tamoxifen reduces the incidence of breast cancer in women who are at increased risk for the disease.

Breast Neoplasms↗
PubMed2000

Progress in cancer chemoprevention: development of diet-derived chemopreventive agents.

Because of their safety and the fact that they are not perceived as "medicine," food-derived products are highly interesting for development as chemopreventive agents that may find widespread, long-term use in populations at normal risk. Numerous diet-derived agents are included among the >40 promising agents and agent combinations that are being evaluated clinically as chemopreventive agents for major cancer targets including breast, prostate, colon and lung. Examples include green and black tea polyphenols, soy isoflavones, Bowman-Birk soy protease inhibitor, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol, vitamin D, vitamin E, selenium and calcium. Many food-derived agents are extracts, containing multiple compounds or classes of compounds. For developing such agents, the National Cancer Institute (NCI) has advocated codevelopment of a single or a few putative active compounds that are contained in the food-derived agent. The active compounds provide mechanistic and pharmacologic data that may be used to characterize the chemopreventive potential of the extract, and these compounds may find use as chemopreventives in higher risk subjects (patients with precancers or previous cancers). Other critical aspects to developing the food-derived products are careful analysis and definition of the extract to ensure reproducibility (e.g., growth conditions, chromatographic characteristics or composition), and basic science studies to confirm epidemiologic findings associating the food product with cancer prevention.

Biomarkers↗
PubMed2002

Early development of cancer chemoprevention clinical trials: studies of dietary calcium as a chemopreventive agent for human subjects.

Early cancer chemoprevention clinical trials in human subjects had to be carried out with large numbers of subjects studied for long durations, measuring cancer as an end point. However new findings on abnormal epithelial cell growth and development during the multistage evolution of colonic tumors made it possible to carry out chemoprevention clinical trials in several stages, with fewer subjects studied for shorter durations, thus enabling investigators to analyze increasing numbers of chemopreventive agents and nutritional regimens in clinical trials. Supplemental dietary calcium was the first candidate chemopreventive agent studied in this multistage approach in human subjects, as a putative agent for colon cancer prevention. Early- and late-stage intermediate biomarker studies in humans have strongly suggested utility for supplemental dietary calcium to inhibit the development of benign and subsequent malignant colonic neoplasms. Preclinical experimental studies have further demonstrated the ability of increased dietary calcium to inhibit the evolution of colonic tumors when they were induced by targeted mutations, dietary factors, and particularly when given over a long duration of lifespan.

Anticarcinogenic Agents↗
PubMed1994

Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models: methods and results from the NCI Chemoprevention Drug Development Program.

In the NCI, Chemoprevention Branch drug development program, potential chemopreventive agents are evaluated for efficacy against chemical carcinogen-induced tumors in animal models. This paper summarizes the results of 144 agents in 352 tests using various animal efficacy models. Of these results, 146 were positive, representing 85 different agents. The target organs selected for the animals model are representative of high-incidence human cancers. The assays include inhibition of tumors induced by MNU in hamster trachea, DEN in hamster lung, AOM in rat colon (including inhibition of AOM-induced aberrant crypts), MAM in mouse colon, DMBA and MNU in rat mammary glands, DMBA promoted by TPA in mouse skin, and OH-BBN in mouse bladder. The agents tested may be classified into various pharmacological and chemical structural categories that are relevant to their chemopreventive potential. These categories include antiestrogens, antiinflammatories (e.g., NSAIDs), antioxidants, arachidonic acid metabolism inhibitors, GST and GSH enhancers, ODC inhibitors, protein kinase C inhibitors, retinoids and carotenoids, organosulfur compounds, calcium compounds, vitamin D3 and analogs, and phenolic compounds (e.g., flavonoids). The various categories of compounds have different spectra of efficacy in animal models. In hamster lung, GSH-enhancing agents and antioxidants appear to have high potential for inhibiting carcinogenesis. In the colon, NSAIDs and other antiinflammatory agents appear particularly promising. Likewise, NSAIDs are very active in mouse bladder. In rat mammary glands, retinoids and antiestrogens (as would be expected) are efficacious. Several of the chemicals evaluated also appear to be promising chemopreventive agents based on their activity in several of the animal models. Particularly, the ODC inhibitor DFMO was active in the colon, mammary glands, and bladder models, while the dithiolthione, oltipraz, was efficacious in all the models listed above (i.e., lung, colon, mammary glands, skin, and bladder).

Animals↗
PubMed1994

Strategy and planning for chemopreventive drug development: clinical development plans. Chemoprevention Branch and Agent Development Committee. National Cancer Institute.

At the National Cancer Institute, Division of Cancer Prevention and Control, the Chemoprevention Branch and Agent Development Committee develop strategies for efficiently identifying, procuring, and advancing the most promising drugs into clinical trials. Scientific expertise is applied at each phase of development to critically review the testing methods and results, and to establish and apply criteria for evaluating the agents for further development. The Clinical Development Plan, prepared by the Chemoprevention Branch and the Agent Development Committee, is a summary of the status of the agent regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. It also contains the strategy for further development of the drug that addresses pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen Clinical Development Plans are presented here: N-acetyl-l-cysteine (NAC), aspirin, calcium, beta-carotene, 2-difluoromethylornithine (DFMO), DHEA analog 8354, 18 beta-glycyrrhetinic acid, N-(4-hydroxyphenyl)retinamide (4-HPR), ibuprofen, oltipraz, piroxicam, Proscar, sulindac, tamoxifen, vitamin D3 and analogs, and vitamin E. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing chemopreventive drugs.

Clinical Trials as Topic↗
PubMed2006

Chemoprevention of pancreatic cancer: a review of the molecular pathways involved, and evidence for the potential for chemoprevention.

BACKGROUND: Pancreatic cancer has a poor prognosis. The use of drugs or natural agents which inhibit or slow down tumour growth therefore has important potential in the development of future therapies. METHODS: A literature search of the PubMed and ISI Web of Science databases was undertaken to review the current data available on the alterations in signalling pathways found in pancreatic carcinogenesis, in order to identify sites that could be targeted by chemopreventive agents. Several agents of particular relevance to pancreatic cancer were identified, and their possible mechanisms of action reviewed. RESULTS: Chemopreventive agents such as non-steroidal anti-inflammatory drugs, green tea constituents, and antioxidants have been shown to target various steps in intracellular signalling pathways, particularly those controlling cell proliferation and survival. Work on cell lines and animal models has shown that some of these agents may be able to modulate the growth of pancreatic tumours. Initial clinical trials of some chemopreventives in pancreatic cancer have been undertaken, and have yielded mixed results, prompting the need for further studies. CONCLUSION: As the molecular pathology of pancreatic cancer becomes better understood, sites of action of chemopreventive substances have been uncovered. Several agents have shown promising results by their ability to inhibit pancreatic carcinogenesis in laboratory studies. If these effects can be successfully translated into human studies then these agents may prove to be valuable adjuvant therapies in the future.

Antineoplastic Agents↗
PubMed2006

Development of novel cancer chemopreventive agents in Europe--neglected Cinderella or rising phoenix? A critical commentary. ESF Workshop on Cancer Chemoprevention, DKFZ, Heidelberg, September 18-20, 2005.

Agents that prevent cancer, delay its onset, or revert premalignant conditions could have dramatic beneficial impacts on human health. Although there is an urgent need to develop cancer chemopreventive agents, researchers in the field suspect that this area of scientific endeavour in Europe leads a Cinderella existence, both in terms of perception of importance and research funding. In order to review current activities in this prevention field and to seek a consensus position, an exploratory workshop was held in September 2005 at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, sponsored mainly by the European Science Foundation (ESF), and also supported by the European Association for Cancer Research (EACR) and the German Cancer Society (DKG). The 35 experts from European countries and the United States of America assessed state-of-the-art cancer chemoprevention research in Europe. The aims that the workshop organizers had pre-defined were: i) assessment of the usefulness of animal models for agent identification; ii) review of ongoing preclinical and clinical work on novel agents; iii) discussion of potential biomarkers predictive for cancer preventive efficacy; and finally iv) the potential role that European pharmaceutical industries could play in furthering chemopreventive agent development. Overall the workshop aimed at raising awareness among European clinical and laboratory researchers of the importance of the development of novel, efficacious and safe cancer preventive agents.

Antineoplastic Agents↗
PubMed2004

13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group.

Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours. 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC. Synergism between retinoids and interferon in tumoural cell lines have been demonstrated. Based on these data, the Italian Head and Neck Chemoprevention Study Group started a randomized chemoprevention study in patients radically treated for stage III and IV HNSCC. From February 1992 to January 1996, 267 patients were randomized: 126 were allocated to the control group, 126 were randomized to receive 13-cRA at a dose of 0.5 mg/kg per day per os and 15 patients have been assigned to the group of 13-cRA plus interferon alpha2a (IFN-alpha2a) at a dose of 3,000,000 UI 3 times a week (randomization in this arm interrupted due to administrative financial problems). The mean follow-up was 39 months. The 5-year actuarial survival was 58.9% for patients of the 13-cRA group and 57.2% for those of the control group (P=0.94). Among evaluable patients, disease progression was observed in 45 of 123 patients (36.6%) of the 13-cRA group and in 42 of 124 (33.9%) of the control group. The 5-year actuarial relapse-free survival was 48.9% for the 13-cRA group and 55.6% for the control group (P=0.62). Adverse effects, mostly of grade I were reported in 69.4% of treated patients (haematologic disorders, mucositis, conjunctivitis, cutaneous toxicity, hypertriglyceridemia and hypercholesterolemia). Only 5 patients (4.1%) reported grade III-IV toxicity. Low-dose of 13-cRA given for 1 year is ineffective as chemoprevention in patients with radically treated HNSCC.

Adult↗
PubMed2005

Feasibility of performing chemoprevention trials in women at elevated risk of ovarian carcinoma: initial examination of celecoxib as a chemopreventive agent.

BACKGROUND: A pilot study was undertaken to determine the feasibility of examining a COX-2 inhibitor (Celecoxib) as a chemopreventive agent in women at increased risk of ovarian cancer undergoing risk reducing salpingoophorectomy. METHODS: Women at elevated inherited risk of ovarian carcinoma pursuing risk reducing salpingoophorectomy were eligible for this trial. Ten patients were assigned to a control group while 10 patients were administered Celecoxib (400 mg/day) for 3 months prior to surgery. Demographic data at enrollment was collected. Serum, urine, peritoneal fluid, and resected tissues were obtained for correlative laboratory study. Evaluation of serum VEGF alterations was examined using an ELISA-based assay. RESULTS: Enrollment of patients was completed in 16 months. Of 29 eligible patients, 20 enrolled onto the study. One patient from each group did not complete surgical intervention. No significant differences were observed in the enrollment characteristics between the groups. No occult cases of ovarian cancer were identified and no differences in the presence of follicular cyst, hemorrhagic cysts, or inclusion cysts were noted on initial pathologic review. While the mean serum VEGF levels obtained following the administration of a COX-2 inhibitor were lower than the pre-administration in 5 of 6 patients, statistical significance in this difference was not observed (P = 0.359). However, this is most likely due to the small number of serum samples available. CONCLUSION: These results would suggest that chemoprevention trials in ovarian cancer will be eagerly embraced by this patient population.

Adult↗
PubMed2004

Cancer chemopreventive activity of rotenoids from Derris trifoliata.

A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aalpha,12aalpha-12a-hydroxyelliptone ( 3), together with five other known rotenoids. In a search for novel cancer chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of beta-carotene without any cytotoxicity. Deguelin ( 4) and alpha-toxicarol ( 5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.

Animals↗
PubMed1997

Chemoprevention of cancer of uterine cervix: a study on chemoprevention of retinamide II from cervical precancerous lesions.

Dysplasia of the uterine cervix is a recognized precancerous condition. Because of the observed ability of retinoids to suppress various cell lines in vitro, a number of clinical studies have examined the effect these agents have on cervical dysplasia, with the object of developing a means of chemoprevention of cervical malignancies in women at risk. Three cervical cancer chemoprevention trials with Retinamide II (RII) have been conducted at the Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China. A pilot study used RII to intervene in cases of precancerous cervical dysplasia. Twenty-seven women with mild, moderate, or severe cervical dysplasia, pathologically confirmed, were treated by RII suppositories, 10 mg QD, given intravaginally for 6 months (each course lasting 3 months). The results indicated that after the second course, the overall response rate was 96.29% and the complete response rate was 88.89%. In general, side effects were mild. A little cervical and vaginal irritation was well tolerated. In the second double-blind study, patients with precancerous cervical lesions were randomized into two groups, one treated with RII suppository intravaginally and the other with a placebo, once daily for 50 days in two courses. Precancerous lesions in 68.76% of patients in the treatment arm disappeared, with an overall effective rate of 74.29% after two courses of treatment with RII. Its curative effect was approximately that of laser beam radiation and electrocautery (P > 0.05), and differed significantly (P < 0.01) from that of traditional antiinflammatories. RII can be a major measure in prevention and treatment of cervical cancer in high-incidence areas in China. In the third trial, we are conducting a randomized double-blind study placebo controlled, in a high-incidence area of cervical cancer (Xiang-Yuan county, Shang Xi Province, China). At present, the patients are being followed up and the study will be completed after 2 years.

Antineoplastic Agents↗
PubMed1997

Colon cancer chemoprevention: clinical development of aspirin as a chemopreventive agent.

We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE2 and PGF2 alpha and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas > 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation.

Animals↗
PubMed1998

[A novel approach for cancer chemoprevention referred to as "gene-regulating chemoprevention"].

We examined the effect of butyrate on the expression of WAF1, a potent inhibitor of cyclin-dependent kinases, and its relation to growth arrest in a p53-mutated human colon cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth of WiDr and caused G1-phase arrest. WAF1 mRNA was rapidly induced by treatment with 5.0 mM butyrate, and significant WAF1 protein induction was detected. Using several mutant WAF1 promoter fragments, we found that the butyrate responsive elements are specific Sp1 sites. These findings suggest that butyrate arrests the growth of WiDr by activating the WAF1 promoter through specific Sp1 sites in a p53-independent fashion. Based on our results, we propose a novel approach for cancer chemoprevention, which we term "gene-regulating chemoprevention". Our strategy is to activate the potent function of growth-inhibitory genes, which are preserved in cancer cells. WAF1 is a good candidate, because it rarely appears to be mutated in common human tumors, while the p53 gene is frequently mutated. Therefore the p53-independent activation of WAF1 by butyrate could be applied to the prevention of cancer when p53 is mutated.

Butyrates↗
PubMed1996

Risk biomarkers and current strategies for cancer chemoprevention.

Quantifiable, well-characterized cancer risk factors demonstrate the need for chemoprevention and define cohorts for chemopreventive intervention. For chemoprevention, the important cancer risk factors are those that can be measured quantitatively in the subject at risk. These factors, called risk biomarkers, can be used to identify cohorts for chemoprevention. Those modulated by chemopreventive agents may also be used as endpoints in chemoprevention studies. Generally, the risk biomarkers fit into categories based on those previously defined by Hulka: 1) carcinogen exposure, 2) carcinogen exposure/effect, 3) genetic predisposition, 4) intermediate biomarkers of cancer, and 5) previous cancers. Besides their use in characterizing cohorts for chemoprevention trials, some risk biomarkers can be modulated by chemopreventive agents. These biomarkers may be suitable surrogate endpoints for cancer incidence in chemoprevention intervention trials. The criteria for risk biomarkers defining cohorts and serving as endpoints are the same, except that those defining cohorts are not necessarily modulated by chemopreventive agents. A primary criterion is that the biomarkers fit expected biological mechanisms of early carcinogenesis-i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, and short latency compared with cancer. They must occur in sufficient number to allow their biological and statistical evaluation. Further, the biomarkers should be assayed reliably and quantitatively, measured easily, and correlated to cancer incidence. Particularly important for cancer risk screening in normal subjects is the ability to use noninvasive techniques that are highly specific, sensitive, and quantitative. Since carcinogenesis is a multipath process, single biomarkers are difficult to correlate to cancer, as they may appear on only one or a few of the many possible causal pathways. As shown in colorectal carcinogenesis, the risks associated with the presence of biomarkers may be additive or synergistic. That is, the accumulation of genetic lesions is the more important determinant of colorectal cancer compared with the presence of any single lesion. Thus, batteries of biomarker abnormalities, particularly those representing the range of carcinogenesis pathways, may prove more useful than single biomarkers both in characterizing cohorts at risk and defining modulatable risks. Risk biomarkers are already being integrated into many chemoprevention intervention trials. One example is the phase II trial of oltipraz inhibition of carcinogen-DNA adducts in a Chinese population exposed to aflatoxin B1. Also, urine samples from subjects in this trial will be screened for the effect of oltipraz on urinary mutagens. A second example is a chemoprevention protocol developed for patients at high risk for breast cancer; the cohort is defined both by hereditary risk and the presence of biomarker abnormalities. Modulation of the biomarker abnormalities is a proposed endpoint. Also, dysplastic lesions, such as prostatic intraepithelial neoplasia, oral leukoplakia and colorectal adenomas, have been used to define high-risk cohorts and as potential modulatable surrogate endpoints in chemoprevention trials.

Animals↗
PubMed1999

Chemoprevention of epithelial cancers.

Over the past 2 years, new insights into mutator and stromal epithelial cell interactions have enhanced the understanding of the carcinogenesis process and have identified potential new approaches to chemoprevention in diverse epithelial sites. Data testing the efficacy of chemopreventive agents in genetically mutated animal carcinogenesis models as screening tools for chemopreventive agents remain immature and point to a continued need for chemical carcinogenesis models to screen for the potential efficacy of chemopreventive agents. The Breast Cancer Prevention Trial is a published, risk-reduction trial that demonstrated a tamoxifen-induced reduction of the risk for breast cancer and focused attention on the clinical use of chemopreventive agents in healthy women. This trial highlighted the potential chemopreventive activity of selective estrogen-receptor antagonists as chemopreventives for breast cancer. New data from animal and human models continue to support the development of nonsteroidal anti-inflammatory agents as chemopreventives for colorectal cancer. Micronutrient- and diet-intervention trials for colorectal chemoprevention present a mixed picture. Although calcium and vitamin supplements, including folate, reduce the recurrence of adenomatous polyps in humans, the effect is small. Fiber supplementation does not reduce the incidence of polyps or colorectal cancer. New approaches for the chemoprevention of esophageal adenocarcinomas, hepatomas, and squamous cell skin cancers represent promising new approaches to the chemoprevention of epithelial cancers.

Animals↗
PubMed1995

Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary.

Well-designed and conducted Phase II clinical trials are very important to cancer chemoprevention drug development. Three critical aspects govern the design and conduct of these trials--well-characterized agents, suitable cohorts, and reliable biomarkers for measuring efficacy that can serve as surrogate endpoints for cancer incidence. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. Agents that meet these criteria for chemoprevention of cervical cancer include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids, folic acid, antioxidant vitamins and other agents that prevent cellular oxidative damage. Because of the significant cervical cancer risk associated with human papilloma virus (HPV) infection, agents that interfere with the activity of HPV products may also prove to be effective chemopreventives. In endometrium, unopposed estrogen exposure has been associated with cancer incidence. Thus, pure antiestrogens and progestins may be chemopreventive in this tissue. Ovarian cancer risk is correlated to ovulation frequency; therefore, oral contraceptives are potentially chemopreventive in the ovary. Recent clinical observations also suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may be chemopreventive in this tissue. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in endometrium, patients with atypical hyperplasia, fit these criteria. Defining a cohort for a Phase II trial in the ovary is more difficult. This tissue is less accessible for biopsy; consequently, the presence of precancerous lesions is more difficult to confirm. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decrease cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, perhaps appearing on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid solely on biomarkers that do not describe cancer but represent isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis. Chemoprevention trials should be designed to evaluate fully the two or three biomarkers that appear to be the best models of the cancer. Additional biomarkers should be considered only if they can be analyzed efficiently and the sample size allows more important biomarkers to be evaluated completely. Two types of biomarkers that stand out regarding their high correlation to cancer and their ability to be quantified are measures of intraepithelial neoplasia and indicators of cellular proliferation. Measurements made by computer-assisted image analysis that are potentially useful as surrogate endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape (roundness), and texture (DNA distribution patterns); nucleolar size and number of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase fraction and PCNA...

Anticarcinogenic Agents↗
PubMedDate not supplied

Why a statin and/or another proven heart healthy agent should be utilized in the next major cancer chemoprevention trial: part I.

The recent removal of refecoxib (a cyclo-oxygenase II inhibitor), a drug involved in a large prostate cancer chemoprevention trial, and the completion of recruitment for the SELECT cancer chemoprevention trial utilizing selenium and vitamin E should lead researchers to ponder a similar question in cancer chemoprevention. The question of "What agent should be utilized and what clinical trial should designed and conducted next for cancer chemoprevention?" Part I and II of this manuscript attempts to argue that statins or cholesterol-lowering drugs or heart healthy agents are the ideal next choice for a large chemoprevention trial for numerous reasons including: (1) Cardiovascular disease (CVD) has been the number one cause of death in men and women every year in the US since 1900; (2) CVD has been the number one cause of death in the major cancer chemoprevention trials; (3) CVD has been the number one or two cause of death of men and women postdiagnosis of breast, colorectal, and prostate cancer; and (4) the recent potential relationship between certain cancers and dyslipidemia needs to be investigated. What other chemoprevention agent can also boast that in the worst case scenario the number one cause of death in men and women would probably be reduced in this future cancer chemoprevention trial of statins?! The list continues to grow of cancer chemoprevention trials that will probably be either a complete hit or miss. In other words, they will or have reduced the disease of interest with virtually no potential role for reducing the number one cause of death in men and women. The time seems more than overdue for a statin and/or another cholesterol lowering or heart healthy cancer chemoprevention trial.

Adult↗