Subject: NIH GUIDE - RFA CA-91-31 - V20(33) 09/06/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Mon, 09 Sep 91 10:19 EST

Hi Paul,
This is #9 of 11 RFAs for 910906 NIH Guide.
Please post this one to the NIH Listserver as:
RFACA-91-31.910906
More to follow.
   Thanks, M. G. Broaddus
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA CA9131 CA-91-31 P1O1 *****************************************
 
REQUEST FOR APPLICATIONS
 
RFA:  CA-91-31
 
MECHANISMS OF MULTISTAGE CARCINOGENESIS IN THE PROSTATE
 
P.T. 34; K.W. 0715035, 0715085, 0785140, 0755020
 
National Cancer Institute
 
Letter of Intent Receipt Date:  October 1, 1991
Application Receipt Date:  December 20, 1991
 
I. PURPOSE
 
The Chemical and Physical Carcinogenesis Branch, Division of Cancer
Etiology (DCE), National Cancer Institute (NCI), invites
investigator-initiated research grant applications (R01s) to elucidate
the basic, complex mechanisms of multistage carcinogenesis in the
prostate.  New and experienced investigators in relevant fields and
disciplines may apply for research funds to pursue investigations in
animal and human prostatic epithelial cells.
 
New advances in prostate tissue and cell culture (12, 13, 14) and
descriptions of potentially useful (but not yet confirmed) animal models
(9) have been published.  In addition, molecular biology is advancing at
a rapid pace (2), and the general understanding of human carcinogenesis
(14) is improving steadily.  Thus, it is an opportune time to support
prostate carcinogenesis investigations and take advantage of these new
technical developments.  Exploitation of these recent advances may
provide the foundation for major new insights, including identification
of the cellular and molecular mechanisms and environmental causes of
transformation to invasive cancer forms in normal and latent prostatic
epithelial cells.
 
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 Request for
Applications (RFA), Mechanisms of Multistage Carcinogenesis in the
Prostate, is related to the priority area of 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.
 
Applications must be prepared and submitted in accordance with the aims
and requirements described in the following sections.
 
II.  ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit, public and private organizations, such as universities,
colleges, hospitals, laboratories, units of state or local governments,
and eligible agencies of the Federal Government.  Applications from
minority individuals and women are encouraged.
 
III.  MECHANISM OF SUPPORT
 
Support of this program will be through the National Institutes of
Health (NIH) grant-in-aid (R01).  Applicants will be responsible for the
planning, direction, and execution of the proposed project.  Except as
otherwise stated in this RFA, awards will be administered under PHS
grants policy as stated in the Public Health Service Grants Policy
Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1,
1990.
 
This RFA is a one-time solicitation.  Future unsolicited competitive
continuation applications will compete with all other
investigator-initiated applications and be reviewed by the Division of
Research Grants (DRG).  However, should the NCI determine that there is
a sufficient continuing program need, a request for competitive
continuation applications will be announced.  Only recipients of awards
under this RFA will be eligible to apply.
 
Total costs of $1,000,000 per year for five years will be committed to
specifically fund applications submitted in response to this RFA.  It is
anticipated that five to seven awards will be made.  This funding level
is dependent upon the receipt of a sufficient number of applications of
high scientific merit.  The total project period for applications
submitted in response to this RFA not exceed five years.  The earliest
feasible start date for the initial awards will be July 1, 1992.
Although this program is provided for in the financial plans of the NCI,
the award of grants pursuant to this RFA is also contingent upon the
availability of funds for this purpose.
 
IV.  BACKGROUND INFORMATION
 
The incidence of prostate cancer has steadily increased since 1937 to
the point where today it has surpassed lung cancer as the most commonly
diagnosed cancer among males in the United States and is the second
leading cause of cancer deaths in men.  Indeed, there were an estimated
106,000 U.S. men diagnosed with prostatic cancer in 1990 and over 30,000
of those will die of this disease (1).  It is estimated that
approximately 122,000 new cases will be diagnosed in 1991, accounting
for 19% of all male cancers.  Worse still, mortality due to prostate
cancer is two-fold higher in blacks compared to whites in the United
States.  Blacks have the highest rate of prostate cancer in the world.
These figures are projected to become increasingly dismal in the future
because of the rising life expectancy of the American male population
and the fact that late in life no other form of cancer increases in
incidence with age as rapidly as does prostate cancer.  Thus, research
focused on delineating the cellular and molecular mechanisms underlying
the transformation and progression of prostatic epithelial cells is
urgently needed.
 
Compared to other forms of cancer there is very little information
available either on the causes of prostatic cancer or the mechanisms by
which normal prostate epithelial cells develop and progress to latent
and invasive cancer.  Emphasis has traditionally been placed on a
probable role of androgenic hormones because it is known from animal
studies that normal prostatic epithelial cell growth is regulated by
these hormones (2, 3) and prostate cancer is not found in males
castrated before puberty (4).  Other studies, however, have made it
clear that environmental and dietary influences may also be of major
importance.  Epidemiological studies have demonstrated that the
incidence of prostate cancer in Japan (4.3/100,000) is much lower than
in the U.S. (61/100,000).  However, the incidence of prostatic cancer in
first and second generation Japanese men that have migrated to the U.S.
is similar to that of the general American male population (5,6).
Histopathological examinations at autopsy of the prostates of men whose
deaths were due to causes other than cancer have revealed that the
pattern of prostate premalignancy is different from that seen in other
tissues.  It has been observed repeatedly that, regardless of
nationality or geographic locale, by age 50 approximately 30 percent of
all men have histologically detectable latent prostate cancer (7,11).
However, only about 4 percent of American men over age 45 will actually
develop clinically diagnosed prostate cancer.  The percentage is much
smaller in Japanese men (7).  The reason for wide variation in the rate
of progression from latent to invasive cancer is unknown, but it seems
likely that environmental and lifestyle factors may play a significant
role; these need to be delineated.
 
Although prostate cancer is a major medical problem (2), very few
investigators are currently focusing their studies on prostatic
epithelial cell carcinogenesis.  A major impediment to the understanding
of the cause and prevention of prostatic cancer is the lack of
information about the specific cell types and their lineages that are
involved in neoplastic transformation (8).  Another major problem is the
absence of a reliable, confirmed animal model for studying
carcinogenesis of the prostate gland (9).  In contrast to most other
forms of human cancer where there are animal models for human solid
tumors, there is very little information on the metabolic capability of
various types of prostatic cells, both within and between different
population groups.  The metabolism of suspected environmental
carcinogens in these tissues has also been virtually ignored (10).
Finally, the roles played by hormones and diet in initiation and
progression of the disease remain unclear (11).
 
In an attempt to better define the state of knowledge and to identify
future needs for research on prostate cancer, the NCI convened 50
experts and leaders from many disciplines of prostate cancer to
participate in a three-day roundtable meeting in Easton, Maryland, on
May 1-3, 1990.  Together with a wide range of NCI program staff, the
participants discussed important research directions to help stem the
increase and to control this most common form of cancer.  At the
workshop, specific research opportunities in four major areas were
discussed, evaluated, and then reconsidered in a multidisciplinary
manner before final selection and priorities were made.  The four areas
were:  life and death of a prostate cancer cell; natural history,
pathology and prognostic factors; risk factors; and screening, early
detection and diagnosis.  A number of the specific objectives of this
RFA are related to the recently published research priorities identified
at this meeting (15).
 
V. RESEARCH GOALS AND SCOPE
 
The goal of this initiative is to accelerate further understanding of
carcinogenesis in the prostate gland in animals and man.  Integrated
studies are encouraged which would address one or more of the items
listed in the following categories.  While these should not be
considered as the only areas of research opportunity, the following
aspects of prostate carcinogenesis could be included within the proposed
studies:
 
A. Cell Biology and Carcinogenesis.  There is a need to establish
markers that can identify those prostatic epithelial cells which are
undergoing the various transformation steps.  Incumbent in this is the
need to identify the cell(s) at risk.  A major question arises:  Is
transformation restricted only to the putative epithelial stem cell, or
are all of the epithelial cells in the gland potential target cells?  A
critical question in growth control of prostate cells is the regulation
of the cell cycle.  In order to understand the regulation of cell
division in the normal prostate and the disruption of this process in
malignant prostate cells, the regulation by androgens and/or growth
factors of cell cycle proteins such as the protein kinase, cdc-2, and
the cycling protein, cyclin, must be defined.
 
B. Carcinogen Metabolism.  Investigations might include comparisons of
carcinogen metabolism, adduct formation, and repair:  (a) among
prostates derived from individual human donors; (b) between prostatic
and seminal vesicle tissues removed from the same donor; and (c) between
human and animal prostatic tissues.  Two questions remain unanswered:
Do stromal cells, hormonal balance, or variation in nutrients affect
metabolism?  What is the degree of individual variation among humans in
the ability to metabolize carcinogens in the prostate?
 
C. Molecular Mechanisms.  Very little is known at the molecular level
about the specific changes that occur as prostatic epithelial cells
undergo various stages of transformation.  Research might include
studies on:  (a) characterizing oncogene activation as a function of
transformation stage; (b) delineating the effects of activated oncogenes
when transfected into normal and premalignant cells; (c) elucidating the
mechanism(s) whereby putative autocrine growth factor production and/or
abnormal expression of growth factor receptors occurs; (d) ascertaining
if specific aberrations in intercellular signaling pathways accompany
transformation; (e) identifying putative prostate cancer specific
suppressor genes; (f) elucidating the molecular changes that result in
dysfunction of androgen-regulated genes; and (g) determining if specific
chromosomal changes are associated with premalignant and/or malignant
cells.
 
D. Cellular Mechanisms.  Additional research could be focused on:  (a)
determining if epithelial/mesenchymal interactions play any role in the
carcinogenesis process; (b) measuring the degree of cell-cell
communication among prostatic cells and ascertaining whether alterations
in the pattern of communication correlate with either the emergence of
the latent tumor phenotype and/or the progression of the latent tumor to
clinically apparent malignancy; (c) assaying for growth factors in
prostate tissue and seminal fluid; (d) evaluating whether, during any
specific stage(s) of the carcinogenesis process, the cell begins to
produce autocrine growth factors or express receptors for growth factors
that the normal cell (or perhaps the latent tumor phenotype) does not
recognize; (e) establishing specific changes in the growth factor,
hormone, nutrient and ion requirements for growth; (f) determining if
the loss of responsiveness by the cells to putative growth inhibitors
(e.g., hormones, pH, interferons, tumor necrosis factors) occurs during
tumor progression; and (g) quantifying changes in cell surface,
cytoplasmic and nuclear antigens.
 
E. Appropriate Models.  Presently, there are no established in vitro or
animal models that have proven to be adequate for studying all of the
aspects of prostate epithelial cell carcinogenesis.  Thus, the
development of a reproducible, practical method for the experimental
induction of prostatic adenocarcinoma is needed.  Animal models must
incorporate as many of the histopathological aspects of the human
disease as possible and, ideally, the tumor should metastasize to the
bone and other tissues.  Optimally, in vitro systems should provide for
the reproducible transformation of epithelial cells through the
recognizable stages of latent and malignant tumor cells when assessed in
an isogeneic or immunologically incompetent host.  In addition, because
of possible species differences, it is desirable that tissue culture
systems include human prostatic cells.  Finally, the model systems
should be amenable to use as a screening procedure for assessing whether
the rate of transformation can be affected by diet/culture medium
composition, hormones, viral/microbial infection, transfected
(autocrine) growth factor genes, oncogene activation, and/or the dose
and chemical nature of carcinogens and tumor promoters.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
 
The inclusion of women is standard terminology for all grants and
contracts; however, due to the specific subject of this RFA, i.e.,
Prostate cancer, the inclusion of women is not applicable.  However, the
inclusion of minorities remains relevant.
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study.  Although inclusion of women is not relevant to
this RFA, special emphasis should be placed on the need for inclusion of
minorities in studies of diseases, such as prostate cancer, which
disproportionately affect them.  This policy is intended to apply to
persons of all ages.  If minorities are excluded or inadequately
represented in clinical research, particularly in proposed
population-based studies, a clear and compelling rationale should be
provided.  The composition of the proposed study population must be
described in terms of gender and racial/ethnic group, together with a
rationale for its choice.  In addition, gender and racial/ethnic issues
should be addressed in developing a research design and sample size
appropriate for the scientific objectives of the study.  This
information should be included in the form PHS 398 in Section 2, A-D of
the Research Plan AND summarized in Section 2, E, Human Subjects.
 
Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However, the
NIH recognizes that it may not be feasible or appropriate in all
research projects to include representation of the full array of United
States racial/ethnic minority populations [i.e., Native Americans
(including American Indians or Alaskan Natives), Asian/Pacific
Islanders, Blacks, Hispanics].  The rationale for studies on single
minority population groups should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
 
The usual NIH policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded.  However, every effort
should be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.
 
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.
 
If the required information is not contained within the application, the
application will be returned.
 
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.
 
All applications for clinical research submitted to the NIH are required
to address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.
 
VI.  REVIEW PROCEDURES AND CRITERIA
 
A. REVIEW PROCEDURE
 
Upon receipt, applications will be reviewed initially by the DRG for
completeness.  Incomplete applications will be returned to the applicant
without further consideration.  Evaluation for responsiveness to the RFA
is an NCI program staff function.  Applications will be judged to
determine how well they meet the goals and objectives of the program as
described in the RFA.  Applications judged non-responsive will be
returned but may be submitted as investigator-initiated research
applications at the next receipt date.  Questions concerning the
relevance of proposed research to the RFA are to be directed to the
Program Director as described in INQUIRIES.
 
If the number of applications is large compared to the number of awards
to be made, the NCI may conduct a preliminary scientific peer review to
eliminate those applications that are clearly not competitive.  The NCI
will withdraw from further competition those applications judged to be
noncompetitive and notify the applicant and institutional business
official.
 
Those applications judged to be both competitive and responsive will be
further evaluated according to the review criteria stated below for
scientific and technical merit by an appropriate peer review group
convened by the Division of Extramural Activities, NCI.  The second
level of review by the National Cancer Advisory Board considers the
special needs of the Institute and the priorities of the National Cancer
Program.
 
B. REVIEW CRITERIA
 
Applications responsive to this competitive solicitation will be
reviewed in accordance with the criteria stated below:
 
o scientific merit, feasibility, and originality of the proposed
research;
 
o technical adequacy and sufficiency of scientific methodology proposed
to reach research objectives;
 
o research experience, competence, commitment, and time availability of
the Principal Investigator and proposed staff and/or collaborators to
perform the proposed studies;
 
o documentation of the adequacy of existing/proposed facilities,
equipment, and resources of all laboratories involved in the research
efforts, e.g., patient populations, specimens.  (This consideration will
include laboratory safety, biohazard, and animal welfare practices and
procedures.); and
 
o appropriateness of requested budget relative to the work proposed and
appropriateness of the timetable for completion.
 
The review group will critically examine the submitted budget and will
recommend an appropriate budget and period of support for each approved
application.
 
VII.  METHOD OF APPLYING
 
The most recent revision of the research grant application form PHS 398
(revised 10/88) must be used in applying for these grants.  The
application package is available at most institutional business offices;
from the Office of Grants Inquiries, Division of Research Grants,
National Institutes of Health, Westwood Building, Room 449, 5333
Westbard Avenue, Bethesda, MD 20892, telephone (301) 496-7441; and from
the NCI Program Director named below.
 
The RFA label available in the 10/88 revision of application form PHS
398 must be affixed to the bottom of the face page.  Failure to use this
label could result in delayed processing of the application such that it
may not reach the review committee in time for review.  In addition, the
RFA number and title must be typed on line 2 of the face page of the
application form.
 
Submit a signed, typewritten original of the application, including the
Checklist, and four signed, exact photocopies, in one package to the DRG
at the address below.  The photocopies must be clear and single sided.
 
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
**The mailing address given for sending applications to the Division of
Research Grants is the ZIP code address for the National Institutes of
Health.  Applicants who use express mail or a courier service are
advised to follow the carrier's requirements for showing a street
address.  The address of the Westwood Building is:  5333 Westbard
Avenue, Bethesda, MD 20816.
 
At time of submission, two additional copies of the application must be
sent to:
 
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 838
5333 Westbard Avenue
Bethesda, MD  20892
 
If the applicant has an approved assurance covering the research
(multiple project assurance for animal subjects), the applicant must
provide with the application certification of Institutional Review Group
(IRG) approval if humans are involved, and verification of the
Institutional Animal Care and Use Committee (IACUC) approval if animals
are involved.  These reviews and approvals must occur prior to
submission of the application for award and the certifications and
verifications must be submitted with the application.  Failure to
provide required certifications and verifications within the application
may result in deferral or rejection.  If animals or humans will be
subjects of the research at performance sites other than the applicant
organization, the applicant must identify, within the application, the
assurance status of each participant.  Failure to provide this
information within the application may result in deferral or rejection.
 
Applications must be received by close of business December 20, 1991.
If an application is received after that date, it will be returned.  If
the application submitted in response to this RFA is substantially
similar to a grant application already submitted to the NIH for review,
but has not yet been reviewed, the applicant will be asked to withdraw
either the pending application or the new one.  Simultaneous submission
of identical applications will not be allowed, nor will essentially
identical applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this RFA
that is essentially identical to one that has already been reviewed.
This does not preclude the submission f substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.
 
VIII.  LETTER OF INTENT
 
Prospective applicants are asked to submit, by October 1, 1991, a letter
of intent that includes a descriptive title of the proposed research,
the name and address of the Principal Investigator, the names of other
key personnel, the participating institutions, and the number and title
of the RFA in response to which the application is being submitted.
 
Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, it is requested in
order to provide an indication of the number and scope of applications
to be reviewed.  The letter of intent should be sent to:
 
Dr. David G. Longfellow
Chief, Chemical and Physical Carcinogenesis Branch
Division of Cancer Etiology
National Cancer Institute
Executive Plaza North, Suite 700
Bethesda, MD  20892
Telephone: (301) 496-5471
FAX:  (301) 496-1040
 
The mailing address given is the ZIP code address for the National
Institutes of Health.  Applicants who use express mail or a courier
service are advised to follow the carrier's requirements for showing a
street address.  The address of Executive Plaza North is:  6130
Executive Boulevard, Rockville, MD 20852.
 
IX.  INQUIRIES
 
Written and telephone inquiries concerning the objectives and scope of
this RFA, and inquiries about whether or not specific proposed research
would be responsive, are encouraged and are to be directed to Dr.
Longfellow at the above address.  The Program Director welcomes the
opportunity to clarify any issues or questions from potential
applicants.
 
Written and telephone inquiries of a budgetary, administrative, and/or
policy nature are to be directed to:
 
Ms. Sara Stone
Grants Management Team Leader
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, Ext. 66
FAX:  (301) 496-8601
 
X. AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance
No. 93.393, Cancer Cause and Prevention Research.  Awards are made under
the authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285)
and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review.
 
REFERENCES
 
1.  Silverburg, E.S., Boring, C.C., and Squires, T.S. Cancer statistics
1990.  CA-A Cancer Journal for Clinicians, 40:  9-26, 1990.
 
2.  Coffey, D.S. and Pienta, K.J. New concepts in studying the control
of normal and cancer growth of the prostate.  In:  D.S. Coffey, N.
Bruchovsky, W. A. Gardner, Jr., M.I. Resnick, and J.P. Karr (eds.),
Current Concepts and Approaches to the Study of Prostate Cancer, pp.
1-73.  New York:  Alan R. Liss, Inc., 1987.
 
3.  Barrack, E.R., and Tindall, D.J., Coffey, D.S. and Pienta, K.J. A
critical evaluation of the use of androgen receptor assays to predict
the androgen responsiveness of prostatic cancer.  In:  D.S. Coffey, N.
Bruchovsky, W.A. Gardner, Jr., M.I. Resnick, and J. P. Karr (eds.),
Current Concepts and Approaches to the Study of Prostate Cancer, pp.
155-187.  New York:  Alan R. Liss, Inc., 1987.
 
4.  Paulson, D.F., Perez, C.A., and Anderson, T. In:  V.T. DeVita, Jr.,
S. Hellman, and S.A. Rosenberg (eds.), Cancer Principles and Practice in
Oncology, pp.  735-785.  Philadelphia:  J.B. Lippincott, 1982.
 
5.  Akazaki, K. and Stemmermann, G.N. Comparative study of latent
carcinoma of the prostate among Japanese in Japan and Hawaii.  JNCI, 50:
1137-1144, 1973.
 
6.  Isaacs, J.T. Prevention of prostatic carcinogenesis - is it
realistic?  In:  D.S. Coffey, M.I. Resnick, A. Dorr, and J.P. Karr
(eds.), The Management of Prostate Cancer, pp.  25-34.  New York:
Plenum Publishing Corporation, 1988.
 
7.  Strahan, R.W. Carcinoma of the prostate:  incidence, origin,
pathology.  J. Urol., 89:  875-880, 1963.
 
8.  Donjacour, A.A., Cunha, G.R., and Sugimura, Y. Heterogeneity of
structure and function in the mouse prostate.  In:  D.S. Coffey, N.
Bruchovsky, W.A. Gardner, Jr., M.I. Resnick, and J.P. Karr (eds.),
Current Concepts and Approaches to the Study of Prostate Cancer, pp.
583-600.  New York:  Alan R. Liss, Inc., 1987.
 
9.  Isaacs, J.T. Development and characteristics of the available animal
model systems for the study of prostatic cancer.  In:  D.S. Coffey, N.
Bruchovsky, W.A. Gardner, Jr., M.I. Resnick, and J.P. Karr (eds.),
Current Concepts and Approaches to the Study of Prostate Cancer, pp.
513-576.  New York:  Alan R. Liss, Inc., 1987.
 
10.  Heatfield, B.M. In vitro models:  organ explant culture of normal
and neoplastic human prostate.  In:  D.S. Coffey, N. Bruchovsky, W.A.
Gardner, Jr., M.I. Resnick, and J.P. Karr (eds.), Current Concepts and
Approaches to the Study of Prostate Cancer, pp.  391-471.  New York:
Alan R. Liss, Inc., 1987.
 
11.  Greenwald, P. In:  D. Schottenfeld, and J.F. Fraumeni (eds.),
Cancer Epidemiology and Prevention, pp.  938-946.  Philadelphia:  W.B.
Saunders, 1982.
 
12.  Lechner, J.F. Replicative cultures of human prostatic epithelial
cells.  In:  D.S. Coffey, N. Bruchovsky, W.A. Gardner, Jr., M.I.
Resnick, and J.P. Karr (eds.), Current Concepts and Approaches to the
Study of Prostate Cancer, pp.  497-509.  New York:  Alan R. Liss, Inc.,
1987.
 
13.  Merchant, D.J. Primary culture as an in vitro model.  In:  D.S.
Coffey, N. Bruchovsky, W.A. Gardner, Jr., M.I. Resnick, and J.P. Karr
(eds.), Current Concepts and Approaches to the Study of Prostate Cancer,
pp.  473-495.  New York:  Alan R. Liss, Inc., 1987.
 
14.  Harris, C.C. Human tissues and cells in carcinogenesis research.
Cancer Res., 47:  1-10, 1987.
 
15.  Chiarodo, A. Meeting Report.  National Cancer Institute roundtable
on prostate cancer:  future research directions.  Cancer Research 51:
2498-2505, 1991.