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Long-term chemical carcinogenesis experiments for identifying potential human cancer hazards: collective database of the National Cancer Institute and National Toxicology Program (1976-1991).

The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology Program (NTP). The extensive files contain, among other sets of information, detailed pathology data on more than 400 long-term (most often 24-month) chemical carcinogenesis studies, comprising nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nanotechnology: Emerging Developments and Early Detection of Cancer. A two-day workshop sponsored by the National Cancer Institute and the National Institute of Standards and Technology, August 30-31 2001, on the National Institute of Standards and Technology Campus, Gaithersburg, MD, USA.

A recent meeting jointly sponsored by the National Cancer Institute (NCI) and National Institute of Standards and Technology (NIST) brought together researchers active in nanotechnology and cancer molecular biology to discuss and evaluate the interface between disciplines. Emerging areas where nanotechnologies may impact cancer prevention and early cancer detection were elaborated by key researchers who catalyzed interdisciplinary dialogue aimed at fostering cross-discipline communications and future collaboration.

Biomarkers, Tumor↗

National cancer institute perspectives.

The National Cancer Institute (NCI) Perspectives this year presented information on the systemic targeted radionuclide therapy (STaRT) research projects: (1) being investigated at the NCI's Intramural Center for Cancer Research; (2) funded by NCI's Radiation Research Program and other extramural programs; and (3) the appropriate National Institutes of Health/NCI funding mechanisms applicable to researchers for obtaining funds for STaRT projects.

Antibodies, Monoclonal↗

Therapy: state-of-the-art assessment of quality. The National Cancer Institute perspective.

The National Cancer Institute (NCI) has a broad spectrum of responsibilities that range from support of basic laboratory research to the clinical testing of new therapeutics and, finally, the dissemination of results of this research to the practicing physician and the public. The reduction of cancer mortality is largely dependent on the responsibility for widespread application of state-of-the-art cancer treatments. A major cancer control focus of the NCI over the last decade has been the development and implementation of programs designed to improve awareness, access and application of state-of-the-art cancer treatment. In addition to the computerized Physician Data Query system, three targeted programs, the Cooperative Group Outreach Program (CGOP), the Community Hospital Oncology Program (CHOP), and the Community Clinical Oncology Program (CCOP) have all been aimed at establishing mechanisms to facilitate the transfer of new patient care technology; and, thereby, provide the highest quality cancer treatment in the community setting. An evaluation was conducted to determine if patterns and outcomes of cancer care management changed over time, and whether this could be related to the presence of CGOP, CHOP, and CCOP. Measurement of required program implementation was relatively straightforward. However, measurement of resultant changes in "quality of care" and the factors that influence physician performance are complex and controversial. Critical elements in the treatment of breast, colon, rectum, and small cell lung cancer were used as tracers to measure changes in the patterns of care in communities where programs were implemented. Results from this study highlight issues in state-of-the-art assessment of quality, such as the difficulty in defining quality cancer care, relationships between process and outcome indicators, and the problems of documentation and missing data. Assurance of quality cancer care requires the interaction of health care professionals with knowledge of the most up-to-date cancer research results working in a health care delivery system that encourages and rewards application of these results.

Clinical Trials as Topic↗

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↗

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/ TRICARE; coverage of phase II and phase III clinical trials sponsored by the National Institutes of Health National Cancer Institute. Final rule.

The final rule allows the Department of Defense to waive normal requirements so that covered beneficiaries can participate in Phase II and Phase III clinical trials sponsored or approved by the National Institutes of Health National Cancer Institute (NIH NCI). This waiver authority is expected to promote beneficiary access to promising new treatments and contribute to the development of such treatments.

Clinical Trials, Phase II as Topic↗

Standards for plasma and serum proteomics in early cancer detection: a needs assessment report from the national institute of standards and technology--National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18-19, 2005.

NIST and the National Cancer Institute cosponsored a workshop on August 18-19, 2005, to examine needs for reference materials for early cancer detection. This meeting focused on standards, methods, assays, reagents, and technologies. Needs for plasma and serum proteomics, DNA methylation, and specimen reference collections were discussed, and recommendations from participants were solicited. This report summarizes the discussion and recommendations for proteomics reference materials.

Biomarkers, Tumor↗

Education and training programs at the National Cancer Institute: 1938-1982.

The National Cancer Institute (NCI) has supported cancer research training and clinical cancer education since 1938, the latter in a variety of forms. These include direct clinical fellowships, followed by institutional grants designed to improve the education of students concerning cancer in medical and dental schools, and subsequently in teaching hospitals. The institutional grants went through three stages between 1948 and 1982, and have recently entered a fourth. Undergraduate Cancer Training Grants supported cancer teaching for medical and dental students. Clinical Cancer Training Grants expanded teaching activities to include post-resident trainees and medical and dental practitioners. Clinical Cancer Education Grants further extended cancer education and emphasized goals, objectives and evaluation, and focused on areas of weakness in cancer teaching such as epidemiology and cancer, cancer prevention and the role of radiation therapy. The various pressures within and without NCI that have influenced the development of these grant programs are discussed. Some cancer education activities supported by Cancer Control programs, both at NCI and another agency of the Public Health Service, are briefly mentioned. Aspects of the grant review process, program monitoring, and the impact of a professional organization developed in direct response to the first institutional cancer education grant program are described.

Cancer Care Facilities↗

Morphometric analysis of bovine lymphomas classified according to the National Cancer Institute Working Formulation.

The National Cancer Institute Working Formulation (NCI-WF) for the subjective classification of human non-Hodgkin's lymphoma is readily applicable to the classification of bovine lymphomas. Forty-nine cases of bovine lymphoma were analysed morphometrically to see if nuclear size and cleavage were distributed continuously or discretely between different NCI-WF tumour cell types. The mean nuclear area (+/- standard error of the mean, SE) was significantly greater (P < 10(-6)) in cells from the different types of diffuse large-cell lymphoma than in cells from the different types of small-cell lymphoma (42.91 +/- 1.21 micron 2 vs 19.33 +/- 1.08 micron 2, respectively); there was no overlap between the two groups. The mean nuclear are (+/- SE) of cells from diffuse large-cell lymphomas was significantly greater (P < 10(-4)) than that of cells from small non-cleaved lymphomas (42.74 +/- 1.72 micron 2 vs 27.54 +/- 1.08 micron 2, respectively), and there was again no overlap between the two groups; these two cell types are difficult to distinguish by any criteria other than size. Additionally, the cell-to-cell variability in nuclear area within a given tumour was significantly greater (P < 0.001) for the diffuse large-cell type than for the small non-cleaved cell type. The mean nuclear form factor (+/- SE) and mean nuclear contour indices (+/- SE) of the diffuse large cleaved cell type (0.53 +/- 0.02 and 5.08 +/- 0.11, respectively) were significantly different (P < 0.01 to 10(-6)) from the same parameters in the diffuse large-cell type (0.82 +/- 0.01 and 3.94 +/- 0.04, respectively). Some of the major criteria of the NCI-WF used subjectively to discriminate between bovine lymphoma cell types were supported by morphometric measurements. The magnitude of the differences in nuclear morphological characteristics between bovine lymphoma cell types was such that there was no overlap.

Animals↗

Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada.

The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

Adult↗

The National Cancer Institute's cancer information service: a new generation of service and research to the nation.

The National Cancer Institute (NCI), the nation's leading agency for cancer information and research, mandated by the U.S. Congress to provide accurate, up-to-date information about cancer to all segments of the U.S. population, established the Cancer Information Service (CIS) on July 1, 1975. Using a two-pronged approach, the telephone information service and education programs for the public and health professionals, the CIS was designed to maximize its reach. In 1982, the CIS implemented three tools: the Call Record Form to record data about each call to the service, a national user survey, and a system of national test calls. These resulted in a rich data source and an infrastructure that allowed collaborative health communications research with the CIS to emerge later in the decade. As the CIS embarks on a new generation of service to the nation, it is now characterized by three vital components that advance the NCI's overall mission of cancer prevention and control: a Partnership Program, Multichannel Contact Centers, and a Health Communications Research Program.

Communication↗

Reevaluation of lung cancer risk in the acrylonitrile cohort study of the National Cancer Institute and the National Institute for Occupational Safety and Health.

OBJECTIVES: The present study provides additional analyses of data obtained earlier on lung cancer risk among workers with acrylonitrile exposure. METHODS: The original authors provided the data. For total mortality and the cancer sites of a priori interest (lung, stomach, brain, breast, prostate, and the lymphatic and hematopoietic systems), standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were computed, the total United States and surrounding counties being used as standard populations. Regional rate-based SMR values were also computed between lung cancer and cumulative acrylonitrile exposure. RESULTS: Except for lung cancer, the external comparisons corroborated the earlier internal comparisons (no increased cancer mortality risk). For lung cancer, the external comparisons revealed death deficits for the unexposed workers (SMR 0.68, 95% CI 0.5-0.9) and all categories of acrylonitrile-exposed workers. The SMR obtained using external rates and the most exposed group (SMR 0.92. 95% CI 0.6-1.4) differed from the corresponding relative risk (RR) of the internal rates (RR 1.5, 95% CI 0.9-2.4). CONCLUSIONS: The analysis of the present study provides little evidence that acrylonitrile exposure increases the mortality risk of cancers of a priori interest, including lung cancer. The lung cancer findings of the external comparison differed from the earlier findings of the internal comparisons. Selection bias (as the healthy worker effect) was probably not responsible. Additional follow-up and analyses, especially of the unexposed workers with low lung cancer rates, may help elucidate the internal and external comparison differences. Results from both comparisons should be presented when the relative risks differ markedly, as both have advantages and disadvantages.

Acrylonitrile↗

The National Cancer Institute audit of the National Surgical Adjuvant Breast and Bowel Project Protocol B-06.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-06, a clinical trial sponsored by the National Cancer Institute (NCI), has provided evidence of the value of lumpectomy and breast irradiation for treating women with breast cancer in an early stage. Publicity generated by the discovery that the study included fraudulent data on patients enrolled by St. Luc Hospital in Montreal aroused concern about the overall accuracy of the data and conclusions. To address this concern, the NCI conducted an audit of other participating institutions. METHODS: In 1994, data on 1554 of the 1809 randomized patients (85.9 percent) enrolled by centers other than St. Luc Hospital were audited at 37 clinical sites in North America. The audit included data on eligibility, survival, disease-free survival, the length of time to a recurrence of cancer in the ipsilateral breast, and documentation of signed informed consent. RESULTS: End points were assessed for all 1554 patients, and eligibility was assessed for 1507 patients; 47 patients were excluded because their forms were not complete or not returned. A total of 1429 patients had their eligibility status verified. Of a total of 7770 data points examined with respect to the number of positive nodes at base line, treatment characteristics, first events (excluding death), recurrence of cancer in the ipsilateral breast, and survival, 7577 (97.5 percent) were verified, 123 (1.6 percent) could not be verified, and 70 (0.9 percent) were discrepant with the NSABP file. Of the 1554 patients, 1340 (86.2 percent) had all audited items (including eligibility) verified, 69 (4.4 percent) had at least one discrepant item, and 113 (7.3 percent) had at least one unverified item (as a result of missing or incomplete data); 32 (2.1 percent) were not assessed for eligibility but had no other discrepant or unverifiable items. Written informed consent was documented for 1098 patients before surgery and 210 after surgery; no date appeared on the signed form for 137. The informed-consent status was not verified for 71 patients and could not be determined for 38. The rates of verification of end-point data and documentation of written informed consent were similar among the total-mastectomy group, the lumpectomy group, and the group treated by lumpectomy and breast irradiation. CONCLUSIONS: The audit confirms the adequacy of the data on which the reanalysis of Protocol B-06 and the results after 12 years of follow-up are based.

Breast Neoplasms↗