Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Cell & Developmental Biology  (31)
  • Molecular Cell Biology  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Development of chemopreventive agents for lung and upper aerodigestive tract cancers (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 2-17 
    Details
    ISSN: 0730-2312
    Keywords: Chemoprevention ; neoplasms ; head and neck ; lung ; esophagus ; oral cavity ; trachea ; intermediate biomarkers ; surrogate endpoints ; clinical trials ; hamster ; strain A mice ; rat ; pharynx ; larynx ; aerodigestive tract ; retinoids ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The lung and upper aerodigestive tract (oral cavity, larynx, pharynx, upper esophagus) will harbor the greatest proportion (≍20%) of estimated new cancer cases in 1992. The estimated mortality rate is even higher (32%), which is reflected in a 5-year survival rate of only 7% and 12% for esophageal and lung cancer, respectively. Tobacco use appears to remain the major cause of aerodigestive cancers despite efforts at primary prevention - cessation of exposure. Another strategy to decrease this public health problem is secondary prevention or chemoprevention. Cancer chemoprevention is defined as intervention with chemical agents before invasion to halt ro slow the carcinogenic process; potential agents may include minor dietary constituents and pharmaceuticals.The main objective of the Division of Cancer Prevention and Control (DCPC), National Cancer Institute, is to develop promising chemopreventive drugs for use in humans. The testing of cancer chemopreventives for efficacy in the clinic differs from that of cancer treatment drugs. Chemopreventive drug trials involve healthy target populations, and the endpoints are reduced cancer incidence or mortality, or increased latency, with no to minimal toxicity. The lung and upper aerodigestive tract represent a unique opportunity for intervention in this setting. Even with cessation of tobacco exposure, the risk of cancer in the entire epithelium remains high for years due to the “field cancerization” effect. Some of the first chemopreventive trials made use of this system due to the availability of a study population with a tissue at demonstrably high risk for malignant progression. Much of the evidence for chemopreventive efficacy is in the oral cavity because of the well-defined epithelial neoplastic progression, the existence of well-established preclinical models, and relative ease of tissue monitoring and sampling. In one of the first randomized trials, Hong and co-workers demonstrated that 13-cis-retinoic acid prevents the appearance of second primary tumors in patients previously treated for squamous cell carcinomas of the oral cavity and upper respiratory tract.Even using a high risk population, chemoprevention trials involve large sample sizes, lengthy duration and follow-up, and high cost. To circumvent these problems, the use of intermediate biomarkers as surrogate endpoints is being explored. Intermediate biomarkers are defined as biological alterations in tissue (histological, genetic, biochemical, proliferative, differentiation-related) occurring prior to cancer development. In the oral cavity, studies using modulation of a histological intermediate biomarker, dysplastic leukoplakia, as the endpoint have demonstrated response to a retinoid.Several problems still need to be addressed in the chemoprevention of aerodigestive cancer, such as the toxicity of some of the agents which have been used (retinoids) and maintenance of remission after cessation of treatment. In addition, clinical chemoprevention trials in the other sites of the aerodigestive system, such as lung and upper esophagus, are not as well advanced. This is due to sampling and monitoring problems and less well-defined premalignant lesions. The DCPC is developing new strategies for chemopreventive trials in the aerodigestive tract.
    Additional Material: 6 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531003
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Guidance for development of chemopreventive agents (1994)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 56 (1994), S. 25-31 
    Details
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240560904
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Chemopreventive effect of perillyl alcohol on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced tumorigenesis in (C3H/HeJ X A/J)F1 mouse lung (1997)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 67 (1997), S. 20-25 
    Details
    ISSN: 0730-2312
    Keywords: CAAX motif ; farnesyltransferase inhibitor ; K-ras ; lung cancer ; monoterpene ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This study was designed to test the chemopreventive potential of perillyl alcohol, an inhibitor of farnesyltransferase, in a mouse lung tumor bioassay. Perillyl alcohol is a naturally occurring monoterpene found in lavender, cherries, and mint. We have shown previously that the majority of lung tumors in this bioassay have an activating mutation in the K-ras gene, which occurs early in the development of mouse lung carcinogenesis. The Ras protein undergoes a series of post-translational modifications, the first of which is farnesylation at the cysteine of the C-terminal CAAX motif. These modifications lead to the anchoring of Ras p21 to the plasma membrane in its biologically active state. Activated Ras p21 couples growth regulatory signals from receptor tyrosine kinases to cytoplasmic second messengers. In a preliminary study, we determined the maximum tolerated dose of perillyl alcohol to be 75 mg/kg body weight. For the bioassay, 5-week-old male (C3H/HeJ X A/J) F1 hybrid mice were randomized into trial groups, and treated with perillyl alcohol three times per week i.p., starting 1 week prior to initiation with the carcinogen NNK, and continuing for 22 weeks after initiation. Our results show a 22% reduction in tumor incidence, and a 58% reduction in tumor multiplicity. Our study demonstrates that perillyl alcohol is an effective chemopreventive compound in the mouse lung tumor bioassay. J. Cell. Biochem. Suppl. 27:20-25. © 1998 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
  • 4
    Electronic Resource
    Electronic Resource
    Introductory remarks: Development of chemopreventive agents for prostate cancer (1992)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 50 (1992), S. 1-8 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; clinical trials ; intermediate biomarkers ; prostate ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The term “cancer chemoprevention” refers to the prevention of cancer by intervening with drugs prior to the malignant (i.e., invasive) stage of carcinogenesis. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch at the National Cancer Institute.The testing of drug for cancer chemoprevention differs from testing of those for cancer treatment. Chemopreventive drug trials involve healthy target populations, and the endpoints of reduced cancer incidence or mortality, reduced/eliminated precancerous lesions, or increased latency must be achieved with little or no drug toxicity.The design of cancer chemoprevention trials for prostate presents several problems, such as the age of the study population and undependable methods for detecting microscopic foci by sequential sampling. A major motivation for organizing this workshop is the development of strategies for the design of chemopreventive intervention trials for prostate cancer.One of the most difficult problems of chemoprevention drug testing is the necessity of lengthy trials due to the long developmental period of many cancers. This is especially true for prostate cancer. A major solution to the problem is the use of intermediate biomarkers, defined as morphological or molecular intraepithelial changes that can constitute short-term endpoints in chemoprevention clinical trials. They are categorized as histological, genetic, proliferation-related, and differentiation-related. Modulation of intermediate biomarkers, instead of cancer incidence, as trial endpoints would allow chemoprevention trials to be of shorter duration, to use fewer subjects, and to be of lower cost. Review of the current status of prostatic intermediate biomarkers, and methods for identifying and validating them, are also major reason for convening this workshop. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240501203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Intraepithelial and postinvasive neoplasia as a stochastic continuum of clonal evolution, and its relationship to mechanisms of chemopreventive drug action (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 14-25 
    Details
    ISSN: 0730-2312
    Keywords: Clonal evolution ; intraepithelial neoplasia ; mitogenesis ; mutagenesis ; neoplastic progression ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The progression of intraepithelial and postinvasive neoplasia depends on the occurrence of clonal evolution, defined as the continuous development of mutations and selective clonal expansions in the neoplastic cell population. The two continuously repeating events of clonal evolution, mutation and clonal expansion, occur at unpredictable times and locations. Therefore the neoplastic process is best characterized as a stochastic, i.e., probabilistic, continuum. The rate of intraepithelial neoplastic progression is continuously driven by the dosage level of exposure to mutagens and mitogens. For example, in chronic smokers the length of time before development of lung cancer depends on the number of cigarettes smoked per day.A commonly held misconception is that human carcinogenesis develops after an initial short period of mutation followed by a long period of stimulated proliferation (the multistage model). This incorrect idea derives from the sequential nature of the consecutive two- or three-step operational protocols imposed on experimental animal models by the experimenter. In reality, human carcinogenesis develops as the result of simultaneous and continuous exposure to mutagens and mitogens over the entire period of tumor development. A recent example is the finding that the intraepithelial neoplasia of colorectal adenomas continuously progresses through serial waves of mutation and clonal expansion.The rational design of chemopreventive agents should be based on blocking the two parameters which continuously drive neoplasia: mutagenesis and mitogenesis. In addition to blocking exposure, chemopreventive agents may act at many points during activation and DNA adduction of mutagens, or during stimulation of the proliferation signal pathway by mitogens. Based on the chemopreventive strategy of blocking mutagenesis and mitogenesis, chemopreventive agents are classed as either antimutagenic or antimitogenic. A third class, the antioxidants, are both antimutagenic and antimitogenic, and operate by the common mechanism of breaking free radical chain reactions initiated by reactive oxygen species. In the program of the Chemoprevention Investigational Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, preclinical development of antimutagens, antimitogens, and antioxidants is well under way, and some of these agents are highlighted here.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531104
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Breast cancer chemoprevention clinical trials (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 219-219 
    Details
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531140
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Selection criteria for breast cancer chemoprevention subjects (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 234-241 
    Details
    ISSN: 0730-2312
    Keywords: Breast cancer risk ; chemoprevention ; intermediate biomarkers ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Early phase chemoprevention trials differ from standard therapeutic clinical trials because asymptomatic, healthy people are treated with a potentially toxic intervention for a prolonged period of time. Current subject selection protocols have relied upon epidemiological methods to identify highrisk individuals. Most available data provide risk estimates for various individual risk factors, but few have reported risk estimates for combinations of risk factors. Selection criteria for the large tamoxifen intervention trial (NSABP P1) were developed from the work of Gail et al. [1]. The Gail model takes into account non-genetic factors (e.g., nulliparity, age at menarche, preexisting pathological conditions) and genetic factors (family history). Using a lifetime risk of 10% of developing breast cancer as a standard to intervention trial. This approach has been criticized for being insufficiently selective (i.e., all women ≥60 yrs), but appears to be the best available method to select subjects for a chemoprevention trial. Other approaches have been based on identification of very high-risk women with acknowledged pathologic conditions [lobular carcinoma in situ, ductal carcinoma in situ (DCIS)]. Attempting to use these proliferative lesions as pathologic endpoints for drug effect has not been attempted. DCIS as a risk factor for tamoxifen intervention was excluded because of controversies over its management and because of frequent difficulties in distinguishing microinvasive from non-invasive lesions. Women treated for early stage breast cancer (Stage I) may be subjects for early stage chemopreventive interventions.We propose the use of intermediate endpoint biomarkers and genetic markers as entry criteria for early phase chemoprevention trials. For colorectal cancer chemoprevention, we have used a two-step selection process. The first step was based on epidemiologic risk assessment. Entry into the study required that a potential intermediate biomarker be positive and quantifiable. The relationship between modulation of a pre-transformational biomarker and development of cancer ultimately needs proof in a primary interventional trial; however, this methodology may permit screening of potential chemopreventive agents at lower cost and more rapid turn-around times. In early chemopreventive agent testing for breast cancer chemoprevention, we propose a similar two-step procedure. Epidemiological and/or pathological criteria for risk would be followed by a procedure to obtain cellular material. The cellular material would be assayed for pre-transformational cellular change.Identifying predictive genes in familial breast cancer cohorts such as the modified BRCA1 gene promises to select individuals at high familial and potentially physiological or environmental risk. The identification of the abnormal gene product in individuals and families will provide another important group of subjects for chemopreventive interventions. The identification of high-risk subjects for breast cancer chemoprevention, particularly those with familial genetic risk, carries important ethical problems. Such women may have difficulties obtaining health and life insurance, deciding to have children, and obtaining work. Chemoprevention trials with genetic selection criteria will need to develop methods of dealing with these issues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531143
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Chemoprevention of rat mammary carcinogenesis: Exceptional activity of dietary dehydroepiandrosterone (DHEA) (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 253-254 
    Details
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A major determinant of progress in human breast cancer prevention is the identification of agents with significant anticarcinogenic activity and acceptable levels of toxicity in experimental animals. Over the past 20 years, more than 50 experimental regimens have been shown to have significant chemopreventive activity in the rat mammary gland. The most effective approaches to mammary cancer chemoprevention in rats involve surgical endocrine ablations such as bilateral ovariectomy. However, prophylactic surgical ablations are unlikely to be acceptable to the majority of the general public. All chemicals evaluated to date are less effective, and none has been shown to reduce mammary cancer incidence to zero. As a result, efforts continue to identify chemical agents whose protective activity is comparable to that of endocrine ablation. DHEA is an adrenal steroid with chemopreventive activity in several animal models for human cancer. In the present studies, the chemopreventive efficacy of DHEA was evaluated in rats exposed to the mammary gland carcinogen, N-methyl-N-nitrosourea (MNU). Groups of 20 female Sprague-Dawley rats were fed an AIN-76A diet supplemented with 0, 400, or 800 mg DHEA per kg diet; one week later, all rats received a single i.p. injection of 35 mg MNU per kg body weight. Animals were palpated weekly to monitor mammary tumor development, and all mammary tumors were histologically confirmed. When administered at 800 mg/kg diet, DHEA reduced mammary cancer incidence in controls from 95% to 15%; carcinoma multiplicity in rats receiving 800 mg DHEA per kg diet was reduced by more than 85% from control levels. In a separate study, the 400 mg/kg diet dose of DHEA reduced the incidence of mammary cancer to 5% from 80% found in controls fed the basal diet. Reductions in mammary cancer incidence and multiplicity associated with DHEA administration were accompanied by large increases in cancer latency. Evaluation of mammary gland wholemounts from animals fed DHEA demonstrated a massive induction of lobuloalveolar differentiation. These results indicate the dietary supplementation with non-toxic dose levels of DHEA has chemopreventive efficacy approaching that of endocrine ablation. This protection may be mediated by the induction of differentiation in the mammary gland, during which sensitive mammary parenchymal structures (terminal end buds) are stimulated to develop into structures (alveolar buds) less sensitive to carcinogenic insult.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531154
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Mechanistic considerations in chemopreventive drug development (1994)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 56 (1994), S. 1-24 
    Details
    ISSN: 0730-2312
    Keywords: Chemoprevention ; drug development ; mechanism of action ; cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This overview of the potential mechanisms of chemopreventive activity will provide the conceptual groundwork for chemopreventive drug discovery, leading to structure-activity and mechanistic studies that identify and evaluate new agents. Possible mechanisms of chemopreventive activity with examples of promising agents include carcinogen blocking activities such as inhibition of carcinogen uptake (calcium), inhibition of formation or activation of carcinogen (arylalkyl isothiocyanates, DHEA, NSAIDs, polyphenols), deactivation or detoxification of carcinogen (oltipraz, other GSH-enhancing agents), preventing carcinogen binding to DNA (oltipraz, polyphenols), and enhancing the level or fidelity of DNA repair (NAC, protease inhibitors). Chemopreventive antioxidant activities include scavenging reactive electrophiles (GSH-enhancing agents), scavenging oxygen radicals (polyphenols, vitamin E), and inhibiting arachidonic acid metabolism (glycyrrhetinic acid, NAC, NSAIDs, polyphenols, tamoxifen). Antiproliferation/antiprogression activities include modulation of signal transduction (glycyrrhetinic acid, NSAIDs, polyphenols, retinoids, tamoxifen), modulation of hormonal and growth factor activity (NSAIDs, retinoids, tamoxifen), inhibition of aberrant oncogene activity (genistein, NSAIDs, monoterpenes), inhibition of polyamine metabolism (DFMO, retinoids, tamoxifen), induction of terminal differentiation (calcium, retinoids, vitamin D3), restoration of immune response (NSAIDs, selenium, vitamin E), enhancing intercellular communication (carotenoids, retinoids), restoration of tumor suppressor function, induction of programmed cell death (apoptosis) (butyric acid, genistein, retinoids, tamoxifen), correction of DNA methylation imbalances (folic acid), inhibition of angiogenesis (genistein, retionoids, tamoxifen), inhibition of basement membrane degradation (protease inhibitors), and activation of antimetastasis genes.A systematic drug development program for chemopreventive agents is only possible with continuing research into mechanisms of action and thoughtful application of the mechanisms to new drug design and discovery. One approach is to construct pharmacological activity profiles for promising agents. These profiles are compared among the promising agents and with untested compounds to identify similarities. Classical structure-activity studies are used to find optimal agents (high efficacy with low toxicity) based on good lead agents. Studies evaluating tissue-specific and pharmacokinetic parameters are very important. A final approach is design of mechanism-based assays and identification of mechanism-based intermediate biomarkers for evaluation of chemopreventive efficacy. 1994 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240560903
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Strategies for phase II cancer chemoprevention trials: Cervix, endometrium, and ovary (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 59 (1995), S. 1-9 
    Details
    ISSN: 0730-2312
    Keywords: Cervical cancer ; cervical intraepithelial neophsia (CIN) ; chemoprevention ; computer-assisted image analysis ; endometrial cancer ; intermediate biomarkers ; ovarian cancer ; Phase II trials ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: 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-wellcharacterized 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 cemopreventive 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 decreased 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 relying 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 FCNA CIN and atypical endometrial hyperplasia are both examples of intraepithelial neoplasia that meet the biomarker criteria and are the basis for quantifiable surrogate endpoints for Phase II chemoprevention trials.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240590902
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...