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At least 19 recordsLinked to original sources
PubMed1994

Chemoprevention research at the U.S. National Cancer Institute.

The use of specific chemicals to prevent the development or retard the progression of carcinogenesis--known as chemoprevention--is a rapidly growing area in cancer research. Developed through the integration of strong laboratory and epidemiologic evidence, chemoprevention research has moved successfully into the clinical research setting, with diverse agents being tested for their efficacy in individuals at high risk of developing certain cancers. The public health potential for reducing cancer incidence and mortality through chemical intervention provides a unique and promising opportunity, and continued support of this multidisciplinary approach to cancer prevention remains a high priority for the U.S. National Cancer Institute.

Antineoplastic Agents↗
PubMedDate not supplied

Information oncologic tools produced by the U.S. National Cancer Institute: how much are they known and used? Results of an enquiry in Italy.

A survey was conducted among specialized users in order to establish the level of knowledge and diffusion of four informative tools: Cancerlit, PDQ, Clinprot, Cancergram. A questionnaire was distributed to 975 graduate researchers working in four national cancer research institutes in the north (2), center (1) and south (1) of Italy, as well as to the students of the Postgraduate School of Oncology (Oncology 2nd) of the "La Sapienza" University of Rome. Respondents were 486 (49.8%): only 167 (34.4%) declared to know Cancerlit, 56 (11.5%) PDQ, 10 (2%) Clinprot and 39 (8%) Cancergrams. Moreover, there is a time gap of nearly 6 years between the availability on-line of these tools and the information of its existence by the users. Most of the respondents were in favor of inserting courses on the use of information tools into the University curriculum and of training in the use of the tools.

Databases, Factual↗
PubMed1994

Overview of U.S. National Cancer Institute (USNCI) chemoprevention research.

The National Cancer Institute's (NCI) chemoprevention plan employs a strategy of basic and epidemiologic studies, followed by a structured preclinical process to bring chemopreventive agents into clinical testing. The field of chemoprevention is progressing rapidly and has reached the point where a coordinated international approach for large-scale trials would be useful. At present, NCI is sponsoring nine large trials (over $1 million per year per trial); in addition, nine agents are in phase I or II clinical testing. A number of these agents should be ready soon for phase III testing. Resources required for large-scale trials compel greater attention to efficient trial design, concept development and review, priority setting, management, budgeting, and collaboration.

Antineoplastic Agents↗
PubMed1994

Predictive statistics and artificial intelligence in the U.S. National Cancer Institute's Drug Discovery Program for Cancer and AIDS.

The National Cancer Institute's drug discovery program screens more than 20,000 chemical compounds and natural products a year for activity against a panel of 60 tumor cell lines in vitro. The result is an information-rich database of patterns that form the basis for what we term an "information-intensive" approach to the process of drug discovery. The first step was a demonstration, both by statistical methods (including the program COMPARE) and by neural networks, that patterns of activity in the screen can be used to predict a compound's mechanism of action. Given this finding, the overall plan has been to develop three large matrices of information: the first (designated A) gives the pattern of activity for each compound tested against each cell line in the screen; the second (S) encodes any of a number of types of 2-D or 3-D structural motifs for each compound; the third (T) indicates each cell's expression of molecular targets (e.g., from 2-dimensional protein gel electrophoresis). Construction and updating of these matrices is an ongoing process. The matrices can be concatenated in various ways to test a variety of specific hypotheses about compounds screened, as well as to "prioritize" candidate compounds for testing. To aid in these efforts, we have developed the DISCOVERY program package, which integrates the matrix data for visual pattern recognition. The "information-intensive" approach summarized here in some senses serves to bridge the perceived gap between screening and structure-based drug design.

Antineoplastic Agents↗
PubMedDate not supplied

The impact of the U.S. Preventive Services Task Force guidelines on cancer screening: perspective from the National Cancer Institute.

The U.S. Preventive Services Task Force evaluated the medical literature, utilizing strict criteria to judge the merits of experimental trials designed to show benefit in screening for cancer. For individuals at normal risk, the task force was not able to make recommendations for or against screening for colorectal, prostate, skin, oral, or testicular cancers. Only one physical-examination cancer-screening procedure has ever been tested in a randomized trial. During the past 27 years, the National Cancer Institute (NCI) has funded six randomized screening trials. Thus far, only one has shown a decrease in mortality. Recognizing the limitations of such trials, the NCI published "Working Guidelines for Early Cancer Detection." Designed for the practicing physician, these guidelines were based upon the best available evidence and on the judgment of representatives of medical professional organizations.

Health Planning Guidelines↗
PubMed2003

Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma.

BACKGROUND: Prior studies have demonstrated that women who receive adjuvant radiation therapy (RT) after mastectomy for breast carcinoma have an increased risk of a second primary lung carcinoma after 10 years, but, to the authors' knowledge, the risk associated with adjuvant RT after breast-conserving surgery (lumpectomy) has yet to be determined. The purpose of the current study was to confirm and extend earlier findings of the effects of postmastectomy RT on second primary lung carcinoma and to investigate the impact of postlumpectomy RT on second primary lung carcinoma in the same population and to compare the results. METHODS: The authors used data from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute, encompassing approximately 10% of the U.S. population, from 1973 to 1998. Of the women with nonmetastatic invasive breast carcinoma, 194,981 had been treated with mastectomy and 65,560 were treated with lumpectomy. Cox regression analysis was used to estimate the relative risk (RR) of a second primary lung carcinoma among women treated with RT compared with those who received surgery alone as a function of time interval since treatment and laterality for both types of surgery. RESULTS: Although no statistically significant elevation in risk for second primary lung carcinoma prior to 10 years was observed, the authors estimated a RR of 2.06 (95% confidence interval [95% CI], 1.53-2.78) and 2.09 (95% CI, 1.50-2.90) for ipsilateral lung carcinoma at 10-14 years and 15+ years after postmastectomy RT, respectively, whereas no increased risk was observed for the contralateral lung. The excess risk of ipsilateral lung carcinoma after postmastectomy RT was found for all three major histologic subtypes of lung carcinoma (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). No increased risk of lung carcinoma was observed at 10-14 years after postlumpectomy RT for either lung. CONCLUSIONS: Postmastectomy RT was found to provide a moderate increase in risk for ipsilateral lung carcinoma starting 10 years after exposure; this increased risk is reported to persist to at least 20 years. Postlumpectomy RT does not appear to incur an increased risk. These findings should be reassuring to women treated with either type of RT, but the excess risk in the postmastectomy group should be considered in the choice between treatment options.

Adult↗
PubMed1996

Colorectal cancer screening.

The decision whether to launch a screening program in asymptomatic patients of average risk for colorectal cancer and the selection of the appropriate protocol for screening are complex issues. There are still many unanswered questions. Many organizations such as the American Cancer Society, the World Health Organization Collaborating Center for the Prevention of Colorectal Cancer, and the U.S. National Cancer Institute advocate screening with annual Hemoccult tests and screening with flexible sigmoidoscopy every 3 to 5 years in patients more than 50 years of age. The U.S. Preventive Services Task Force, the Canadian Task Force on Periodic Health Examination, and the International Union Against Cancer have not recommended screening asymptomatic average-risk patients for colorectal cancer. One study showed a small but significant benefit (3 per 1000) of the rehydrated annual Hemoccult test in reducing mortality from colorectal cancer. To embark on a mass screening strategy as recommended, however, would require significant costs, increases in physician training, improved access to the requisite technology, and enhancements in patient and physician compliance. Furthermore, the high false-positive rates of the rehydrated Hemoccult tests would lead to many unnecessary tests, causing greater expense as well as patient discomfort and anxiety. It is, therefore, premature to recommend mass screening for colorectal cancer in asymptomatic individuals at this time. Further research is needed to identify risk factors (such as genetic markers) better and to develop and evaluate screening strategies targeted at those with high risk for colorectal cancer. In the meantime, efforts at primary prevention for the general population should be increased (through nutrition and exercise). Patients over the age of 50 who desire screening should be given information of the benefits and risks of screening and together with their physicians decide on a screening strategy that suits their needs and values.

Colonoscopy↗
PubMed1987

Keynote lecture. Etiologic insights from cancer mapping.

In the 1970s the epidemiology program at the U.S. National Cancer Institute made a systematic effort to identify cancer clustering by analyzing patterns of mortality at the county level, where the population is small enough to be relatively homogeneous, yet large enough to provide reliable data and stable rates. When the mortality rates for the period 1950-69 were plotted in a series of computer-generated color-coded maps, there arose a surprising number and variety of geographic patterns. This review describes how leads to the causes of several cancers have been generated and explored through a progression of descriptive and correlational studies, followed by analytical studies to determine reasons for the elevated risks in certain areas of the country. For example, the high lung cancer rates among men in some coastal areas were related mainly to asbestos exposures in shipyard work, while the elevated oral cancer rates among women in the rural south were linked to the use of smokeless tobacco (snuff). A recent update of cancer maps covering the period 1970-80 revealed geographic patterns resembling those in the earlier atlas, but with a tendency toward greater uniformity of rates around the country. Yet some new high-risk areas emerged, such as elevated rates of lung and oral cancers among women in Florida and along the Pacific coast, which seemed correlated with smoking habits, and high rates of non-Hodgkin's lymphoma among men in central areas that may be associated with agricultural exposure to herbicides. Our experience suggests that cancer mapping on a small-area scale is a useful strategy for formulating and pursuing leads to environmental and lifestyle determinants of cancer. In other countries also, the mapping approach has helped to stimulate and target research into the origins of cancer and the means of prevention.

Demography↗
PubMed2001

Radiolabeled sentinel node biopsy: collaborative trial with the National Cancer Institute.

The objective of this study was to maximize the success rate of sentinel node (SN) localization in breast cancer patients with the tracer that demonstrated the highest initial success during a preliminary evaluation. Altogether, 145 patients with operable invasive breast cancer and clinically negative lymph nodes were studied. Technetium 99m (99mTc)-sulfur colloid was injected into the breast parenchyma surrounding the invasive cancer or the biopsy cavity. Variable volumes of tracer, amounts of 99mTc, and duration of time between injection and surgery were evaluated. A hand-held gamma detector was used at surgery to locate and guide resection of all radioactive sentinel nodes (SNs), including those that were extraaxillary. A conventional lymphadenectomy was then performed in all cases. Based on previous studies, unfiltered sulfur colloid provided a higher success rate of SN identification than the other tracer types. Further evaluation with 99mTc-sulfur colloid demonstrated that increased volume increased the success rate of SN identification. An injection volume of 8 ml resulted in a success rate of 98%. SNs were not exclusively located in the axilla: In 8.6% of cases SNs were removed from an internal mammary location. The overall accuracy of patients with SNs resected was 98.4%, and the false-negative rate was 4.4%. It was concluded that (1) unfiltered 99mTc-sulfur colloid at a volume of 8 ml resulted in a high success rate for SN identification; (2) a significant number of the SNs were extraaxillary in location; and (3) the accuracy of the SNs for determining whether regional metastases had occurred was high. The U.S. National Cancer Institute is funding a randomized phase III clinical trial to evaluate SN resection compared to conventional axillary lymphadenectomy in clinical node-negative breast cancer patients. Major endpoints of this trial include long-term regional control and survival.

Breast Neoplasms↗
PubMed2000

Breast cancer stage at diagnosis and survival among patients with prior breast implants.

Longstanding concern exists regarding the potential for women with breast implants to experience delayed detection of breast cancer. Furthermore, survival among cosmetic breast implant patients who subsequently develop breast cancer is a concern. Since 1976, this institution has monitored cancer incidence in a cohort of 3182 women who underwent cosmetic breast augmentation between 1959 and 1981. The distributions of stage at diagnosis and survival of the 37 women who subsequently developed in situ or invasive breast cancer were compared with the observed population distributions. The distribution of stage at diagnosis for cosmetic breast implant patients who subsequently developed breast cancer was virtually identical to that of all breast cancer patients in Los Angeles County who were of the same age and race, and were diagnosed during the same time period. Furthermore, the 5-year survival rate of the 37 patients did not differ from that which would be expected based on rates established by the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. These results suggest that cosmetic breast implant patients are not at increased risk of delayed detection of breast cancer, nor do they suffer a poorer prognosis when breast cancer does occur. Although the number of breast cancer patients in this study is small, the results are highly consistent with the existing epidemiologic evidence related to breast cancer detection and survival among breast implant patients. Although breast implant patients should continue appropriate breast cancer screening behavior, there seems to be no cause for alarm.

Adult↗
PubMed1991

Is brain cancer mortality increasing in industrial countries?

This paper analyzes age-specific trends in brain and other central nervous system cancer mortality from 1968 to 1987 in several major industrial countries. It also examines changes in the use of diagnostic confirmation technology and trends in incidence in the U.S. National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) program from 1973 to 1987 to estimate the influence of diagnostic factors on recent mortality trends. Other sources of error have not been evaluated in this paper. Age-specific analyses of brain and other nervous system cancer mortality show drastic increases in persons ages 75-84 and consistent increases in younger age groups in most countries, although mortality declined in the U.S. in persons 0-24 by 2% annually. In the SEER program, brain cancer incidence increased significantly by 2%, 1%, and 5% annually in persons aged 0-44, 65-74, and 75-84, respectively. Throughout this time period, microscopic or radiographic confirmation occurred in at least 96% of all incident cases of brain and other central nervous system cancers diagnosed before death, with older persons receiving consistently more radiographic tests than younger persons. Changes in diagnoses across populations and over time are unlikely to account completely for these increasing trends which are occurring simultaneously in both males and females in major industrial countries. Additional studies need to be conducted, to exclude artifacts, to assist health care planners in anticipating treatment demands, and to detect preventable causes of these changing trends.

Adult↗
PubMed1993

Survival from localized breast cancer. Variability across trials and registries.

Age-specific (< 50, 50-69 years) 10-year survival proportions in four European trials for node-negative, Stage I and II breast cancer patients differ significantly. These patients, identified as having the same stage as localized-breast cancer patients in the End Results Registry of the U.S. National Cancer Institute, had pooled survival proportions for the two age groups (0.713, 0.579) close to those of the registry (0.713, 0.607).

Adult↗
PubMed1995

Navigating to knowledge.

One way to fulfill point-of-care knowledge needs is to present caregivers with a visual representation of the available "answers". Using such a representation, caregivers can recognize what they want, rather than have to recall what they need, and then navigate to an appropriate answer. Given selected pieces of information from a computer-based patient record, an interface can anticipate certain knowledge needs by initializing caregiver navigation in a semantic neighborhood of answers likely to be relevant to the patient at hand. These notions draw heavily on two collaborative projects--the U.S. National Library of Medicine Unified Medical Language System and the U.S. National Cancer Institute Knowledge Server. Both of these projects support navigation because they make the structure of medical knowledge explicit in a way that can be exploited by human interfaces.

Artificial Intelligence↗
PubMedDate not supplied

Mining and visualizing large anticancer drug discovery databases.

In order to find more effective anticancer drugs, the U.S. National Cancer Institute (NCI) screens a large number of compounds in vitro against 60 human cancer cell lines from different organs of origin. About 70,000 compounds have been tested in the program since 1990, and each tested compound can be characterized by a vector (i.e., "fingerprint") of 60 anticancer activity, or -[log(GI50)], values. GI50 is the concentration required to inhibit cell growth by 50% compared with untreated controls. Although cell growth inhibitory activity for a single cell line is not very informative, activity patterns across the 60 cell lines can provide incisive information on the mechanisms of action of screened compounds and also on molecular targets and modulators of activity within the cancer cells. Various statistical and artificial intelligence methods, including principal component analysis, hierarchical cluster analysis, stepwise linear regression, multidimensional scaling, neural network modeling, and genetic function approximation, among others, can be used to analyze this large activity database. Mining the database can provide useful information: (a) for the development of anticancer drugs; (b) for a better understanding of the molecular pharmacology of cancer; and (c) for improvement of the drug discovery process.

Algorithms↗
PubMed1998

Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19.

Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).

Animals↗
PubMed1994

Isolation and structure/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii.

Ten halogenated monoterpenes (2-6 and 8-12) related to the novel antitumor compound halomon (1) or to the carbocyclic analog 7 have been isolated from different geographic collections of the red alga, Portieria hornemannii. Structures were assigned to the basis of spectral analyses (primarily NMR and MS). The absolute configuration of isohalomon (2) was further established by X-ray crystallography. The compounds were comparatively evaluated alongside 1 and 7 in the U.S. National Cancer Institute's in vitro human tumor cell line screening panel. The results provide some interesting initial insights into the structure/activity relationships in this series.

Antineoplastic Agents↗