Full Text PA-95-025 APOPTOSIS MODULATORS FOR TREATMENT OF AIDS-RELATED CANCERS NIH GUIDE, Volume 24, Number 4, February 3, 1995 PA NUMBER: PA-95-025 P.T. 34 Keywords: AIDS Cancer/Carcinogenesis Biology, Cellular National Cancer Institute Application Receipt Date: May 1, 1995 PURPOSE The purpose of this Program Announcement is to encourage investigators to discover modulators of the apoptotic process with the intent of developing new therapies for AIDS-related malignancies. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement (PA), Apoptosis Modulators for Treatment of AIDS-Related Cancers, is related to the priority area of human immunodeficiency virus/AIDS and cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications may be submitted from one institution or may include arrangements with several institutions, if appropriate. Applications involving minority institutions are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT Support for this PA will be the investigator-initiated research project grant (R01), FIRST (R29) award, or the Interactive Research Project Grants (IRPG) mechanisms. If an IPRG is proposed, it must consist of a minimum of two independent applications (see PA-94-086, NIH Guide for Grants and Contracts, Volume 23, Number 28, July 29, 1994). An IRPG may consist of a combination of R01s and R29s or R01s only, but may not consist solely of R29 applications. An IRPG may also contain shared interactive resources (Cores), which must serve at least two of the research projects in order to facilitate achievement of the Group's common research goals. Collaborative arrangements involving more than one institution are especially encouraged, including participation of the pharmaceutical industry where appropriate. FUNDS AVAILABLE The NCI has set aside approximately $1.0 million total costs in Fiscal Year 1995 for the first year of funding for support of applications received in response to this PA. The level of support is dependent on the receipt of a sufficient number and diversity of applications of high scientific merit and the availability of funds. Because the nature and scope of the research proposed in response to the PA may vary, the sizes of awards will vary. It is expected that four or five awards will be made. RESEARCH OBJECTIVES Background Human immunodeficiency virus (HIV) infection causes a pronounced decrease in CD4+ T helper cells resulting in loss of immune function. AIDS patients have an unusually large incidence of highly aggressive malignancies related to their attenuated immune functions. New and more effective methods to treat AIDS associated cancers are badly needed. Recent evidence suggests that apoptosis is an important component of cancer therapy. The intrinsic killing power of drugs or radiation may be less important than the ability of these agents to stimulate tumor cells to kill themselves. Apoptosis may also be relevant to some aspects of drug resistance and may explain why tumor cells are more sensitive to cell killing than are normal cells. Exploitation of this concept of tumor cell death for the development of new and more effective therapies provides an exciting and potentially fruitful challenge. Objectives and scope Apoptosis is a topic of considerable research interest. Numerous research projects have been undertaken to delineate the mechanisms and molecular factors that regulate the process. As a result of these efforts, an understanding of apoptosis encompassing a broad range of cellular mechanisms is emerging. The goal of this PA is the exploitation of these exciting advances in the understanding of the mechanism of apoptosis for discovery of modulators of the apoptotic process with the intent of developing new therapies for AIDS-related malignancies. Applications focused on exploitation of current knowledge of apoptosis for the discovery of agents that modulate the process are encouraged. Applications designed solely to understand the basic principles of apoptosis are not encouraged as part of this initiative. Examples of research topics include, but are not limited to: o Altering gene expression or activity of gene products which regulate apoptosis,i.e., p53, c-myc, bcl-2, or bax. o DNA repair mechanisms. o Stimulation of oxidative damage or stress. o Cell signalling mechanisms which influence apoptosis. o Development of in vitro and in vivo model systems for discovery of apoptotic modulators. Applications could include biological evaluation of active agents using these models. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. Investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used. Forms are available at most institutional offices of sponsored research or from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/710-0267. Receipt date for applications for this AIDS-related research PA is May 1, 1995. The title and number of the PA must be typed in Section 2a of the face page of the application. FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. If an IRPG is proposed, each application must be identified along with the number of the PA and the phrase "Investigator-initiated IRPG". All R01 or R29 applications constituting the proposed IRPG cohort must be submitted in a single package, whether or not the applications arise from the same institutions. For detailed instructions for preparations and submission of IRPG applications, refer to PA-94-086, NIH Guide for Grants and Contracts, Volume 23, Number 28, July 29, 1994. A signed, typewritten original of the application and five legible copies must be sent or delivered in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established Public Health Service referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific/technical review, the applications will receive a second-level review by an appropriate National Advisory Council/Board. Applications that are complete and responsive to the program announcement will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA For Fiscal Year 1995, the NCI has set aside $1 million for this initiative. However, applications will compete for funding with all other approved applications, and funding decisions will be based on scientific merit as determined by peer review and programmatic priorities. INQUIRIES Inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. George S. Johnson Division of Cancer Treatment National Cancer Institute Executive Plaza, North, Room 832 Bethesda, MD 20892-7450 Telephone: (301) 496-8783 FAX: (301) 496-8333 Email: meadt@dctod.nci.nih.gov Direct inquiries regarding fiscal matters to: Ms. Marci Bollt Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 243 MSC-7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, ext. 242 FAX: (301) 496-8601 Email: bolltm@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are made under authorization of HHS policies and grant regulations. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke- free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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