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1.
Cancer Epidemiol Biomarkers Prev ; 9(10): 1071-8, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11045790

RESUMO

Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , DNA de Neoplasias/genética , Fenretinida/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Idoso , Antineoplásicos/efeitos adversos , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Fenretinida/efeitos adversos , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento , Bexiga Urinária/patologia
2.
J Natl Cancer Inst ; 91(21): 1847-56, 1999 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-10547391

RESUMO

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/prevenção & controle , Fenretinida/uso terapêutico , Segunda Neoplasia Primária/prevenção & controle , Vitamina A/análogos & derivados , Adulto , Idoso , Anticarcinógenos/uso terapêutico , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Risco , Fatores de Risco , Resultado do Tratamento
3.
Am J Dent ; 11(1): 50-2, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9823087

RESUMO

This article describes a method for efficient and precise tooth preparation for fixed partial dentures. Diagnostic procedures are also reviewed.


Assuntos
Prótese Parcial Fixa , Preparo Prostodôntico do Dente/métodos , Dente Pré-Molar , Dente Suporte , Humanos , Dente Molar
4.
Am J Dent ; 11(5): 199-201, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10388376

RESUMO

This article reviewed clinical conditions that assist selection of specific design decisions for the tooth preparation for cast metal restorations. This decision should result in a conservative restoration for a given clinical situation. A paradigm is included to assist the dentist in the decision-making process.


Assuntos
Técnica de Fundição Odontológica , Preparo da Cavidade Dentária/métodos , Planejamento de Prótese Dentária , Restaurações Intracoronárias , Coroas , Árvores de Decisões , Ligas Dentárias , Humanos , Fraturas dos Dentes/prevenção & controle
5.
J Cell Biochem Suppl ; 25: 1-14, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9027592

RESUMO

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.


Assuntos
Anticarcinógenos/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias/prevenção & controle , Animais , Quimioprevenção , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Humanos , Neoplasias/epidemiologia , Neoplasias/genética , Projetos de Pesquisa , Fatores de Risco
6.
J Cell Biochem Suppl ; 26: 1-28, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9154166

RESUMO

Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being considered, such as vitamin E with l-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are ras isoprenylation and epidermal growth factor receptor inhibitors.


Assuntos
Anticarcinógenos/uso terapêutico , Neoplasias/prevenção & controle , Animais , Ensaios Clínicos como Assunto , Humanos , Neoplasias Experimentais/prevenção & controle
7.
J Cell Biochem Suppl ; 26: 54-71, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9154168

RESUMO

This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs.


Assuntos
Anticarcinógenos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Transformação Celular Neoplásica , Ensaios Clínicos como Assunto/normas , Humanos , Neoplasias Experimentais/prevenção & controle
8.
Am J Dent ; 8(2): 103-4, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7546478

RESUMO

A heat-sterilizable vacuum system (Legend) featuring a skirt technology that confines the user's hand to the sterile instruments during initial hose coupling and during patient treatment is described. Because the user does not grasp the non-sterile vacuum hose connector and hose, plastic barriers and mandatory disinfection of the hose connector, hose, and instrument holders after each patient are not necessary. The vacuum system described promotes asepsis by using sterile vacuum instruments, encourages sound asepsis practice, prevents cross-contamination, and is cost-effective.


Assuntos
Equipamentos Odontológicos , Controle de Infecções/instrumentação , Contaminação de Equipamentos/prevenção & controle , Vácuo
9.
Fundam Appl Toxicol ; 22(3): 341-54, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8050630

RESUMO

The synthetic compound 2-(difluoromethyl)-dl-ornithine irreversibly inhibits ornithine decarboxylase and reduces the intracellular levels of the polyamine cell cycle factors putrescine and spermidine. The drug has shown chemopreventive efficacy in numerous laboratory epithelial cancer models and is a prototype for antiproliferative agents. Chronic toxicity studies in rats and dogs were performed to characterize the toxicities of the compound at high dosages and to support its further development in clinical trials as a potential chemopreventive agent. Chronic administration (52 weeks) by gavage to Charles River CD rats at dosages of 400, 800, and 1600 mg/kg produced weight loss, increased platelets, alopecia and skin abrasions, dermatitis, liver necrosis, and gastric inflammation. The no-effect dose in this study was considered 400 mg/kg. Chronic administration by capsule to dogs at dosages of 50, 100, and 200 mg/kg produced conjunctivitis, hyperkeratosis and alopecia, and cystic intestinal crypts. A no-effect dose was not determined in this study. The toxicities demonstrated in these studies may be minimized at lower dosages and support the further development of this compound in chemopreventive clinical investigations.


Assuntos
Anticarcinógenos/toxicidade , Eflornitina/toxicidade , Animais , Contagem de Células Sanguíneas/efeitos dos fármacos , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Conjuntivite/induzido quimicamente , Conjuntivite/patologia , Dermatite/patologia , Cães , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hemoglobinas/metabolismo , Mucosa Intestinal/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Caracteres Sexuais , Pele/patologia , Especificidade da Espécie
12.
Int J Cancer ; 52(2): 189-96, 1992 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-1521908

RESUMO

Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias/prevenção & controle , Lesões Pré-Cancerosas/química , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/química , Ensaios Clínicos como Assunto , Colo/patologia , Neoplasias do Colo/genética , Avaliação de Medicamentos , Humanos , Mucosa Intestinal/patologia , Cooperação do Paciente , Lesões Pré-Cancerosas/patologia , Prognóstico , Pesquisa , Fatores de Risco , Sensibilidade e Especificidade
13.
Mutat Res ; 267(2): 291-5, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1376431

RESUMO

As part of a program to develop drugs which will delay or prevent cancer in humans, the Chemoprevention Branch, National Cancer Institute, National Institutes of Health, is sponsoring 12 Phase I and 22 Phase II and III clinical trials. Three agent classes are significantly advanced in the trials. These are the retinoids, including 13-cis-retinoic acid, retinol, and 4-hydroxyphenylretinamide (nine studies), beta-carotene (seven studies), and calcium compounds (three studies). In addition, six promising new compounds are in Phase I or Phase II trials. These are: piroxicam, ibuprofen, oltipraz (a dithiolthione), difluoromethylornithine, glycyrrhetinic acid, and N-acetylcysteine. Key concepts related to the development of cancer chemopreventive agents are (1) the need for long-term administration, (2) the need for oral route of administration, (3) the matching of toxic side effects to degree of cancer risk.


Assuntos
Anticarcinógenos/uso terapêutico , Ensaios Clínicos como Assunto , Neoplasias/prevenção & controle , Feminino , Humanos , National Institutes of Health (U.S.) , Estados Unidos
14.
J Cell Biochem Suppl ; 16I: 1-12, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1305671

RESUMO

The term cancer chemoprevention refers to the prevention or prolongation of carcinogenesis by intervention with drugs prior to the malignant (i.e., invasive) stage. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch of the National Cancer Institute. Neoplastic lesions of the urinary bladder present a unique opportunity for evaluating chemopreventive agents because of (1) the accessibility of the lesions to observation and biopsy, and (2) those patients who have been successfully treated for a primary lesion represent a population at unusually high risk for recurrence and/or progression. Although 70-80% of bladder cancers initially present as superficial, papillary transitional cell neoplasms with limited potential for invasion, the incidence of recurrence is high after resection (60-75%). Recurrent tumors are highly unpredictable, and may be of higher grade or stage (progression). Although recurrence is responsible for high treatment-related morbidity, progression represents the greatest potential for mortality. Thus, potential chemopreventive agents considered here would modulate bladder carcinogenesis from initiation of normal-appearing tissue through progression of superficial tumors. Clinical trials of chemopreventive drugs involve healthy target populations, and the endpoints are reduced cancer incidence or mortality, reduced/eliminated precancerous lesions or increased latency, with none to minimal toxicity. Since cancers may not appear for 20-30 years, two of the most difficult aspects of testing these drugs in intervention trials are the long observation periods and large study populations required to measure cancer incidence reduction. However, observing the regression or recurrence of superficial bladder lesions (TIS, T1, Ta) requires relatively short time periods. Thus, these lesions lend themselves to the investigation of intermediate biomarkers, defined as morphologic and/or molecular alterations in tissue between initiation and tumor invasion. It is hypothesized that modulation of one or more biomarkers would interrupt carcinogenesis and result in a decrease in cancer incidence. Thus, evaluation of biomarkers as surrogate endpoints would allow bladder trials to be of even shorter duration, use fewer subjects and be lower in cost. In addition, intermediate biomarkers could predict which superficial lesions (or normal-appearing tissue) have the greatest potential for neoplastic progression. Development of strategies for the design of intervention trials for bladder cancer and review of the current status of intermediate biomarkers in the bladder, and methods for their validation, are major objectives of this workshop.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Bexiga Urinária/prevenção & controle , Animais , Biomarcadores/química , Ensaios Clínicos como Assunto , Humanos , National Institutes of Health (U.S.) , Estados Unidos
15.
J Cell Biochem Suppl ; 16G: 15-21, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1469895

RESUMO

The Chemoprevention Branch of the National Cancer Institute has established a program for the development of safe and effective cancer chemopreventive agents. This program includes identification of new agents, testing for efficacy in vitro and in animals, studies in animals to model clinical use, and preclinical toxicity and metabolism evaluation. Ultimately, the most promising agents progress to clinical trials. The long period required for cancer onset presents a significant challenge to the design of clinical trials for chemoprevention. Phase III trials in which cancer reduction is the endpoint require large subject groups (tens of thousands) and follow-up duration of more than five years. Because of these requirements, the cost of such trials are high. The Chemoprevention Branch is addressing this challenge by expansion of the preclinical and Phase II clinical efficacy efforts to include intermediate biomarkers of carcinogenesis as study endpoints. The Chemoprevention Branch's studies focus on the development of biomarkers with high reliability and predictive value for cancer. Both single markers and batteries of complementary and parallel markers are evaluated. Among the criteria for biomarkers for chemoprevention studies are the following: (1) differential expression in normal and high risk tissue, (2) appearance early in carcinogenesis (the earlier a reliable biomarker appears, the greater is the chance for successful intervention with a chemopreventive agent), (3) high sensitivity, specificity, and accuracy relative to cancer, (4) ease of measurement (use of non-invasive techniques and small tissue samples is preferable), (5) demonstration of modulation by chemopreventive agents, and (6) correlation of modulation with decreased cancer incidence.


Assuntos
Anticarcinógenos/uso terapêutico , Biomarcadores Tumorais/análise , Lesões Pré-Cancerosas/patologia , Diferenciação Celular , Divisão Celular , Ensaios Clínicos como Assunto , Humanos , Lesões Pré-Cancerosas/diagnóstico , Projetos de Pesquisa
16.
J Cell Biochem Suppl ; 16H: 1-8, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1289663

RESUMO

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 drugs 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 reasons for convening this workshop.


Assuntos
Anticarcinógenos/uso terapêutico , Neoplasias da Próstata/prevenção & controle , Animais , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico
17.
Cancer Lett ; 60(2): 177-84, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1657370

RESUMO

We studied the influence of the vitamins retinol acetate, alpha-tocopherol acetate and thiamine chloride; the antioxidant sodium selenite and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine, on the offspring of transplacental carcinogenesis by ethylnitrosourea in rats. Ethylnitrosourea was given to pregnant rats as a single i.v. injection, at a dose of 75 mg/kg body wt. or 5.5 mg/kg body wt., on the 21st day after conception. Retinol, tocopherol or thiamine was added to the diet, and selenite and alpha-difluoromethylornithine to drinking water of the offspring throughout their postnatal life at moderate doses. In control groups, ethylnitrosourea induced tumors of brain, spinal cord, peripheral nervous system and kidneys in the offspring. alpha-Difluoromethylornithine exerted a slight inhibitory effect; this agent decreased the total tumor multiplicity and the multiplicity of peripheral nervous system tumors and also prolonged survival time. Retinol, tocopherol, thiamine and selenite did not influence the development of the transplacentally-induced tumors.


Assuntos
Antioxidantes/farmacologia , Eflornitina/farmacologia , Neoplasias Experimentais/prevenção & controle , Selênio/farmacologia , Vitaminas/farmacologia , alfa-Tocoferol/análogos & derivados , Animais , Diterpenos , Etilnitrosoureia , Feminino , Neoplasias Renais/induzido quimicamente , Troca Materno-Fetal , Neoplasias do Sistema Nervoso/induzido quimicamente , Gravidez , Ratos , Ésteres de Retinil , Selenito de Sódio , Tiamina/farmacologia , Tocoferóis , Vitamina A/administração & dosagem , Vitamina A/análogos & derivados , Vitamina A/farmacologia , Vitamina E/administração & dosagem , Vitamina E/análogos & derivados , Vitamina E/farmacologia
18.
J Prosthet Dent ; 66(4): 439-44, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1791553

RESUMO

Base metal alloys have been widely used for fixed partial dentures in the past decade. The oxidation heat treatment (degassing) of these alloys is a controversial step to prepare the metal surface for bonding porcelain. This study evaluated the effect of oxidation heat treatment on the porcelain bond strength of base metal alloys and investigated composition changes that may have occurred during this process.


Assuntos
Ligas de Cromo/química , Colagem Dentária , Porcelana Dentária/química , Temperatura Alta , Ligas Metalo-Cerâmicas/química , Análise de Variância , Berílio , Prótese Parcial Fixa , Microanálise por Sonda Eletrônica , Humanos , Íons , Teste de Materiais , Resistência à Tração
19.
J Prosthet Dent ; 65(6): 787-9, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2072322

RESUMO

This study compared the shear bond strength of Panavia EX and Comspan Opaque adhesive resins with electrolytically etched or sandblasted Rexillium III or Litecast B metals bonded to extracted teeth. An analysis of variance revealed that there is no difference in bonding strength among etched or sandblasted Rexillium III metal with either Panavia EX or Comspan Opaque resins. With Litecast B metal, sandblasting produced a greater bond strength than etching with Panavia Ex resin (38.19 MPa sandblasted; 30.53 MPa etched). Conversely, Comspan Opaque resin had a value of 30.10 MPa etched and 15.40 MPa sandblasted. The etched Rexillium III and Panavia EX resins recorded a greater bond strength (38.38 MPa) than Comspan Opaque resin (27.83 MPa) or sandblasted Rexillium III metal (Rexillium III 34.74 MPa; Comspan Opaque 20.39 MPa) and Litecast B metal (Panavia EX 38.19 MPa; Comspan Opaque 15.40 MPa). Eighty percent of the failures occurred at the cement-metal interface with both cements.


Assuntos
Condicionamento Ácido do Dente , Adesivos/química , Ligas Dentárias/química , Colagem Dentária , Cimentos de Resina , Resinas Sintéticas/química , Análise de Variância , Cimentação , Ligas de Cromo/química , Cimentos Dentários/química , Análise do Estresse Dentário , Prótese Parcial Fixa , Eletrólise , Humanos , Teste de Materiais , Fosfatos/química , Estresse Mecânico , Propriedades de Superfície , Dente/fisiologia
20.
Am J Clin Nutr ; 53(1 Suppl): 305S-313S, 1991 01.
Artigo em Inglês | MEDLINE | ID: mdl-1985403

RESUMO

Cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials. At present, the chemoprevention program is sponsoring 21 human efficacy studies. These trials are testing the potential of agents (beta-carotene, folic acid, 13-cis retinoic acid, 4-hydroxyphenyl retinamide, vitamins C and E, and minerals) as inhibitors of a variety of cancers in humans (colon, lung, esophagus, cervix, bladder, and skin). Endpoints in these studies include overall incidence of cancer, incidence of specific cancers, rate of regression or progression of preneoplastic changes, and changes in cellular or biochemical parameters. Study participants include volunteers from the general population; populations at high risk for cancer because of occupation, lifestyle, or place of residence; persons with previously treated cancers; and persons with preneoplastic lesions. Study designs include single agent randomization, combination of agents and complete factorial designs.


Assuntos
Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Neoplasias/prevenção & controle , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/prevenção & controle , Neoplasias Experimentais/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina A/uso terapêutico , beta Caroteno
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