RRP Medical Reference Service





An RRP Foundation Publication


edited by


Bill Stern and Michael Green






















Summer 1996



Volume 3 • Number 2













The RRP Medical Reference Service is intended to be of potential interest to RRP patients/families seeking treatment, practitioners providing care, micro biological researchers as well as others interested in developing a comprehensive understanding of recurrent respiratory papillomatosis.

This issue focuses on a selection of references (most) with abstracts from recent (1994 and later) RRP related publications.These listings are sorted in approximate reverse chronological order as indicated by the "Unique Identifier" numbers. Each listing is formatted as follows:
Primary affiliation (when specified)
Language (if it is not specified assume article is in English)
Journal or reference
Unique identifier

If copies of complete articles are desired, we suggest that you request a reprint from one of the authors. If you need assistance in this regard or if you have any other questions or comments please feel free to contact:

Bill Stern
50 Wesleyan Drive
Hamilton Square, NJ 08690
(609)890-0502 or (609)452-6545
Fax: (609)987-5063
AOL: billslins
Internet: wfs@gfdl.gov


RRPF Selected Articles and Abstracts



Luster MI; Wilmer JL; Germolec DR; Spalding J; Yoshida T; Gaido K; Simeonova PP; Burleson FG; Bruccoleri A

Role of keratinocyte-derived cytokines in chemical toxicity.

Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, NIH, Research Tr

Source: Toxicol Lett 1995 Dec;82-83:471-6

Unique Identifier: 96170132


Following appropriate stimulation, such as with tumor promoters,
ultraviolet light or various chemical agents, keratinocytes
synthesize and secrete cytokines which can mediate or participate
in dermatotoxic responses such as inflammation, hyperkeratosis,
hypersensitivity and skin cancer. We have determined the
qualitative and quantitative cytokine response in primary human
keratinocyte cultures following exposure to several
non-sensitizing contact irritants, sensitizers and ulcerative
agents as well as a skin carcinogen. The chemicals were also
administered to mice to assess whether the dermatotoxic response
correlated with the in vitro production of keratinocyte-derived
cytokines. Due to the complex cellular interactions that occur in
the skin, it was not possible to identify specific cytokine
profiles for most of the classes of dermatotoxic agents studied.
However, the non-sensitizing contact irritants produced relative
increases in the synthesis and secretion of the proinflammatory
cytokines, interleukin-1 and tumor necrosis factor-alpha, as well
as the neutrophil chemotactic cytokine, interleukin-8 compared to
the other chemical agents. While ulcerative compounds as well as
irritants elicited neutrophils to the site of chemical
application when applied to the mouse skin, time-dependent and
chemical-specific patterns of inflammation were detected.
Treatment of human keratinocyte cultures with arsenic, a human
skin carcinogen, resulted in a unique cytokine profile
characterized by induction of growth factors, including
transforming growth factor-alpha and granulocyte-macrophage
colony stimulating factor. Treatment of v-Ha-ras transgenic mice,
an animal model for skin cancer, with arsenic caused an increase
in the number of papillomas as well as overexpression of these
growth factors suggesting that they participate in
arsenic-induced skin papilloma development. These studies
indicate a diverse role exists for keratinocyte-derived cytokines
in dermatotoxic actions.


Garfias Cano R; Villarreal Peral C; Juarez Azpilcueta A

[Current concepts on human papillomavirus infection]

Hospital General de Mexico.

Source: Ginecol Obstet Mex 1995 Dec;63:509-13

Unique Identifier: 96151700


The human papilloma virus presents a multidimensional problem for
gynecologist and urologist. The human papilloma virus infection
(HPVI) incidence has been increased, so that at present it's the
viral infection most common of the genital tract. The HPV is
transmitted for sexual contact but it has not been explained the
infection mechanism of the virus-cell interaction of the host.
The long term consequences of the sexual transmission diseases
are more serious in female than in male. The majority have a
little of symptoms, so that frequently they do not receive
treatment, and therefore have pregnancy, sterility and
infertility, transplacental infection of the fetus, preterm and
newborn infection along the contaminated genital tract. In
addition, the genital HPV is associated with cervical dysplasia
and it can be important in the cervical cancer development. The
treatment is multiple and includes cytotoxic agents, surgery,
immunotherapy and laser abrasion.


Jansen KU; Rosolowsky M; Schultz LD; Markus HZ; Cook JC; Donnelly JJ; Martinez D; Ellis RW; Shaw AR

Vaccination with yeast-expressed cottontail rabbit papillomavirus
(CRPV) virus-like particles protects rabbits from CRPV-induced
papilloma formation.

Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.

Source: Vaccine 1995 Nov;13(16):1509-14

Unique Identifier: 96164463


Papillomaviruses infect epithelia of the skin and mucous
membranes and cause benign or malignant tumours in animals and in
humans. The viruses are highly species-specific, and cell culture
systems for propagating human papillomaviruses (HPVs) do not
exist. However, there are several animal papillomavirus models.
In the cottontail rabbit papillomavirus (CRPV) system, we
demonstrated that recombinant CRPV virus-like particles (VLPs)
consisting of the capsid proteins L1 or L1+L2 can be produced in
the yeast Saccharomyces cerevisiae. Three immunizations with L1
VLPs formulated on aluminum adjuvant at 1-100 micrograms dose-1
efficiently protected rabbits from challenge with CRPV. Sera of
immunized rabbits were shown to contain high-titered serum
antibodies to CRPV L1 VLPs and to neutralize CRPV in vitro. Our
results suggest that recombinant yeast-derived VLPs could be the
basis for a candidate HPV vaccine.


Silva RA; Munoz SE; Guzman CA; Evnard AR

Effects of dietary n-3, n-6 and n-9 polyunsaturated fatty acids
on benzo(a)pyrene-induced forestomach tumorigenesis in C57BL6J

Catedra de Histologia, Instituto de Biologia Celular (FCM), Universidad Nacional de Cordoba-CONICET, Argentina.

Source: Prostaglandins Leukot Essent Fatty Acids 1995 Oct;53(4):273-7

Unique Identifier: 96131667


The modulating effect of dietary polyunsaturated fatty acids
(PUFAs) on benzo(a)pyrene-induced forestomach tumorigenesis was
assayed in mice fed with corn oil (CO), olein (O), Zizyphus
mistol seed oil (MO), cod liver oil (CLO), and mixed fat (Stock
diet). The fatty acid composition of liver lipids correlated well
with the fatty acid composition of each diet. Only mice fed the O
diet showed biochemical and clinical evidences of essential fatty
acid deficiency (EFAD). Only 3 animals developed
well-differentiated invading squamous cell carcinomas in the O
group. The papilloma incidence was reduced in MO and CLO with
respect to the O group. Forestomach papillomatosis was increased
in mice fed an n-9 enriched diet in comparison to stock and CO
groups. In comparison with stock mice, the frequency of multiple
epidermoidal hyperplasia (MEH) was significantly decreased in the
CLO group. Animals fed n-3 enriched diets (MO and CLO) showed
significant antipromoting effect. These findings indicate that
dietary fat can modulate tumorigenesis initiated in mouse
forestomach by benzo(a)pyrene. In addition, the lack of action of
an n-6 fatty acid-enriched diet in our experimental model
suggests that the effect of PUFAs on tumorigenesis has
target-tissue specificity. Mistol seed oil might be of potential
value as a natural vegetable antipromoter nutrient.


Donnelly JJ; Martinez D; Jansen KU; Ellis RW; Montgomery DL; Liu MA

Protection against papillomavirus with a polynucleotide vaccine.

Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.

Source: J Infect Dis 1996 Feb;173(2):314-20

Unique Identifier: 96162088


Genital infections with human papillomavirus (HPV) are
increasingly recognized as a significant source of human disease;
HPV is now implicated in up to 90% of cervical carcinomas.
Neutralizing antibodies against papillomaviruses recognize
conformational epitopes formed when viral capsid proteins
assemble into virions or virus-like particles. Immunization with
plasmid DNA encoding the major viral capsid protein L1 was
studied as a means of inducing neutralizing antibodies and
protection against virus challenge. In a cottontail rabbit
papillomavirus (CRPV) model, immunization with plasmid DNA
encoding L1 elicited conformationally specific neutralizing
antibodies and provided immunity against papilloma formation upon
challenge with CRPV. Immunization with DNA encoding the capsid
protein may provide a means of protecting humans against HPV and
would simplify the production of multivalent vaccines by
combining plasmids that encode the viral capsid proteins of
different strains. This may be of importance given the
multiplicity of HPV types capable of causing disease.

Christensen ND; Reed CA; Cladel NM; Han R; Kreider JW

Immunization with viruslike particles induces long-term
protection of rabbits against challenge with cottontail rabbit

Department of Pathology, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

Source: J Virol 1996 Feb;70(2):960-5

Unique Identifier: 96135207


Rabbits were immunized with recombinant baculovirus-produced
virus-like particles (VLPs) of cottontail rabbit papillomavirus
(CRPV) to determine whether these antigens could induce long-term
protection against experimental challenge with CRPV. Infectious
CRPV and human papillomavirus type 11 L1 VLPs were used as
positive and negative control immunogens, respectively. Three
groups of immunized animals were challenged with 10-fold serial
dilutions of infectious CRPV at 2 weeks, 6 months, and 12 months
after immunizations. Antibody titers in serum reached 1:10,000
immediately after the final booster immunization and then decayed
to 1:150 at 6 months and 1:100 at 12 months in unchallenged
rabbits. Serum neutralization titers followed similar kinetics.
Papillomas grew on control-immunized rabbits at sites challenged
with 10(-1) (100% of sites), 10(-2) (96% of sites), 10(-3) (63%
of sites), and 10(-4) (13% of sites) dilutions of virus. At 2
weeks after CRPV L1 VLP immunizations, the rabbits were
completely protected against virus challenge. At both 6 and 12
months after CRPV L1 VLP immunizations, strong protection was
also observed. In the last two groups, three of seven rabbits
were completely protected and only 4 of 14 or 29% of sites
challenged with 10(-1 dilution of virus grew papillomas.
Papillomas growing at these four sites were also reduced in size
(3.5 +/- 0.7 mm) at 50 days postchallenge compared with sites
challenged with 10(-1) dilution on control-immunized rabbits
(13.2 +/- 4.2 mm). The results demonstrate that strong and
long-lasting protection against experimental challenge with
papillomaviruses can be achieved with VLP immunogens.


Lin KY; Guarnieri FG; Staveley-O'Carroll KF; Levitsky HI; August JT; Pardoll DM; Wu TC

Treatment of established tumors with a novel vaccine that
enhances major histocompatibility class II presentation of tumor

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-6417, USA.

Source: Cancer Res 1996 Jan 1;56(1):21-6

Unique Identifier: 96124870


Presentation of antigenic peptides by MHC class II molecules to
CD4+ T cells is critical to the generation of antitumor immunity.
In an attempt to enhance MHC class II antigen processing, we
linked the sorting signals of the lysosome-associated membrane
protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus
(HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
Previously, we found that expression of this chimera in vitro and
in vivo with a recombinant vaccinia vector targeted E7 to
endosomal and lysosomal compartments and enhanced MHC class II
presentation to CD4+ T cells compared to vaccinia expressing
wild-type E7. In the current study, we tested these recombinant
vaccinia for in vivo protection against an E7+ tumor, TC-1, which
was derived from primary epithelial cells of C57BL/6 mice
cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All
mice vaccinated with 1 x 10(7) plaque-forming units of wild-type
E7-vaccinia showed progressive tumor growth when challenged with
a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice
vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor
free 3 months after tumor injection. Furthermore, treatment with
the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small
established TC-1 tumors, whereas the wild-type E7-vaccinia showed
no effect on this established tumor burden. These findings point
out the therapeutic limitations of recombinant vaccinia
expressing unmodified tumor antigens. Further, they demonstrate
that modifications that reroute a cytosolic tumor antigen to the
endosomal/lysosomal compartment can profoundly improve the in
vivo therapeutic potency of recombinant vaccines.


Shapiro AM; Rimell FL; Shoemaker D; Pou A; Stool SE

Tracheotomy in children with juvenile-onset recurrent respiratory
papillomatosis: the Children's Hospital of Pittsburgh experience.

Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, Pennsylvania, USA.

Source: Ann Otol Rhinol Laryngol 1996 Jan;105(1):1-5

Unique Identifier: 96133190


Despite the risk of airway obstruction, tracheotomy has been
viewed with trepidation in the management of recurrent
respiratory papillomatosis (RRP). The literature suggests that
the injury associated with the tracheotomy site may initiate the
progression of disease to the distal airway. Alternatively,
patients who require tracheotomy for RRP may be predisposed to
distal spread because of more aggressive disease. In an effort to
clarify this issue, we reviewed the Children's Hospital of
Pittsburgh experience with 35 patients with RRP between 1984 and
1994; 13 patients received tracheotomies. Tracheotomy patients
presented at a younger age with more widespread disease, often
involving the distal airway prior to tracheotomy. Although distal
spread occurred in 50% of patients, it was generally limited to
the tracheotomy site. Overall, outcome in the tracheotomy group
was satisfactory. Complications related to the tracheotomy were
rare. We conclude that tracheotomy is an appropriate option for
significantly airway compromise in patients with RRP.


Suzich JA; Ghim SJ; Palmer-Hill FJ; White WI; Tamura JK; Bell JA; Newsome JA; Jenson AB; Schlegel R

Systemic immunization with papillomavirus L1 protein completely
prevents the development of viral mucosal papillomas.

MedImmune, Inc., Gaithersburg, MD 20878, USA.

Source: Proc Natl Acad Sci U S A 1995 Dec 5;92(25):11553-7

Unique Identifier: 96102152


Infection of mucosal epithelium by papillomaviruses is
responsible for the induction of genital and oral warts and plays
a critical role in the development of human cervical and
oropharyngeal cancer. We have employed a canine model to develop
a systemic vaccine that completely protects against
experimentally induced oral mucosal papillomas. The major capsid
protein, L1, of canine oral papillomavirus (COPV) was expressed
in Sf9 insect cells in native conformation. L1 protein, which
self-assembled into virus-like particles, was purified on CsCl
gradients and injected intradermally into the foot pad of
beagles. Vaccinated animals developed circulating antibodies
against COPV and became completely resistant to experimental
challenge with COPV. Successful immunization was strictly
dependent upon native L1 protein conformation and L1 type.
Partial protection was achieved with as little as 0.125 ng of L1
protein, and adjuvants appeared useful for prolonging the host
immune response. Serum immunoglobulins passively transferred from
COPV L1-immunized beagles to naive beagles conferred protection
from experimental infection with COPV. Our results indicate the
feasibility of developing a human vaccine to prevent mucosal
papillomas, which can progress to malignancy.

Gomez MA; Drut R; Lojo MM; Drut RM

Detection of human papillomavirus in juvenile laryngeal
papillomatosis using polymerase chain reaction.

Catedra de Genetica Microbiana, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Argentina.

Source: Medicina (B Aires) 1995;55(3):213-7

Unique Identifier: 96093517


We examined the presence and subtypes of human papillomavirus
(HPV) in 20 paraffin-embedded samples (from 12 patients) of
juvenile laryngeal papillomatosis using the polymerase chain
reaction (PCR). The biopsies had been stored for months to 12
years. Due to the great genetic variability of HPV, we selected a
conservative sequence of the viral genome (L1 region) to identify
the vast majority of the subtypes. Positive results were obtained
by one-step PCR amplification with the MY09-11 consensus primers
(L1 region) in only 10 of the cases. After a two-step
amplification (nested-PCR) with GP5-6 primers the 20 samples
proved to be positive demonstrating the higher sensitivity of
this method. In order to amplify a highly variable region of the
genome (E6), specific primers for HPV types 6 and 11 (H6/11
L1-R2) were used. 7/12 patients were positive for this subtype.
Since more that one subtype has been reported in the same sample,
the presence of HPV 6-11 sequences does not exclude that other
subtypes might be involved. The results of this study show that:
1) HPV is present in JLP. 2) The most frequent HPV subtype
involved was from the 6-11 group. 3) PCR can be successfully used
in archived tissue routinely processed in a laboratory of



Schwartz AG; Pashko LL

Cancer prevention with dehydroepiandrosterone and non-androgenic
structural analogs.

Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140,

Source: J Cell Biochem Suppl 1995;22:210-7

Unique Identifier: 96010333


There is increasing evidence that the adrenocortical steroid,
dehydroepiandrosterone (DHEA), is an important mammalian hormone.
Administration of DHEA to laboratory mice and rats inhibits
development of experimental tumors of the breast, lung, colon,
liver, skin and lymphatic tissue. In the two-stage skin
tumorigenesis model in mice, DHEA treatment inhibits tumor
initiation, as well as tumor promoter-induced epidermal
hyperplasia and promotion of papillomas. There is much evidence
that DHEA produces its antiproliferative and tumor preventive
effects by inhibiting glucose-6-phosphate dehydrogenase and the
pentose phosphate pathway. This pathway is an important source of
NADPH, a critical reductant for many biochemical reactions that
generate oxygen free radicals, which may act as second messengers
in stimulating hyperplasia. The therapeutic use of DHEA in humans
may be limited by its sex hormonal side effects. DHEA is
metabolized in vivo to both testosterone and estrone, producing
both androgenic and estrogenic effects in laboratory animals. We
have developed a synthetic steroid, 16
alpha-fluoro-5-androsten-17-one, which does not demonstrate the
androgenic or estrogenic activity of DHEA, yet retains the
antiproliferative and cancer preventive activity of the native


Bradlow HL; Sepkovic DW; Telang NT; Osborne MP

Indole-3-carbinol. A novel approach to breast cancer prevention.

Strang-Cornell Cancer Research Laboratory, New York, New York 10021, USA.

Source: Ann N Y Acad Sci 1995 Sep 30;768:180-200

Unique Identifier: 96098078


The results show that all of the carcinogens, oncogenes, and
tumor-associated viruses that we have studied profoundly affect
the extent of 2- and 16 alpha-hydroxylation in a prorisk
direction. All of the dietary and biological responses associated
with increased cancer risk decrease 2-hydroxylation and increase
16 alpha-hydroxylation. Remarkably, although PAHs are reported to
induce P450-1A1, we have found them to decrease 2-hydroxylation.
Finally, using indole-3-carbinol to induce 2-hydroxylation
results in the chemoprevention of mammary tumors in rodents and
recurrences of laryngeal papillomas in humans. Also correlating
with these studies in HPV is the decrease in the C-2/C-16 alpha
metabolite ratio observed in women with CIN relative to control
subjects. The greatest decrease was observed in women with the
most severe form, CIN3 (Figure 23). These findings are under
further investigation.


Muller R


Klinik und Poliklinik fur Hals-Nasen-Ohren-Heilkunde, Medizinische Fakultat Carl Gustav Carus, Technischen Universitat D

Source: Ther Umsch 1995 Nov;52(11):759-62

Unique Identifier: 96092269


Hoarseness is a cardinal symptom of laryngeal disease. It is a
disturbance of the normal voice pitch that can be evaluated
acoustically using the 'RBH scale' [R for roughness, B for
breathiness, H for hoarseness]. Hoarseness lasting longer than
three weeks or recurring must be evaluated by an ENT specialist
or a phoniatrist. Causes of hoarseness include functional
disorders of the voice, inflammation of the larynx, secondary
changes of the vocal folds, polyps, cysts, edema, papillomas,
tumors, trauma, or palsies of the vocal cords due to different
reasons. Early diagnosis of malignant laryngeal tumors is a
prerequisite for preserving voice quality. Functional disorders
and unilateral palsies of the vocal folds are treated by
logopedists. The therapy of choice for inflammations is relief of
symptoms, and surgery is employed for organic lesions.


Zhu X; Tommasino M; Vousden K; Sadovnikava E; Rappuoli R; Crawford L; Kast M; Melief CJ; Beverley PC; Stauss HJ

Both immunization with protein and recombinant vaccinia virus can
stimulate CTL specific for the E7 protein of human papilloma
virus 16 in H-2d mice.

MCR Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.

Source: Scand J Immunol 1995 Nov;42(5):557-63

Unique Identifier: 96062122


The transforming protein E7 of human papilloma virus type 16 can
stimulate cytotoxic T lymphocytes (CTL) which can protect
experimental animals against growth of E7 expressing tumour
cells. In this study we compared CTL responses in mice immunized
with either E7 protein in MF59 adjuvant or with recombinant
vaccinia virus expressing E7 (Vac-E7). We have chosen H-2d mice
because no E7-specific CTL responses have been described in this
MHC haplotype. Immunization of these mice with Vac-E7 generated
CTL which lysed target cells infected with Vac-E7 or transfected
with the E7 gene. CTL from mice immunized with E7 protein in MF59
adjuvant showed specificity for the same target cells. Antibody
blocking experiments revealed that both immunization with Vac-E7
and E7 protein stimulated CD8+ effector CTL. The find specificity
of CTL induced by the two immunization protocols was similar. A
major CTL epitope was mapped to the carboxyl terminal amino acids
48-98 of the E7 protein. Peptide isolation from E7 expressing
cells followed by HPLC separation indicated that CTL induced by
immunization with protein and Vac-E7 recognized the same HPLC
purified peptide fractions. Together, the study suggests that
vaccines based on protein can activate CTL with similar fine
specificity to CTL induced by vaccines based on recombinant
vaccinia virus.

Li CY; Nagasawa H; Dahlberg WK; Little JB

Diminished capacity for p53 in mediating a radiation-induced G1
arrest in established human tumor cell lines.

Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Source: Oncogene 1995 Nov 2;11(9):1885-92

Unique Identifier: 96068917


It has been reported that the p53 gene mediates an ionizing
radiation-induced G1 arrest in mammalian cells. To further
characterize this important phenomenon, a panel of seven human
diploid fibroblast cell strains and 14 human tumor cell lines
from a variety of sources with both wild-type and mutant p53
status were assayed for their susceptibility to G1 arrest after
gamma-ray irradiation by a continuous labeling [3H]thymidine
incorporation technique. An irreversible G1-block involving
20-70% of the cell population was observed in diploid fibroblasts
irradiated with 4 Gy. The block was abolished by transfection
with the Human Papilloma Virus E6 gene and in an ataxia
telangiectasia (AT) cell line, indicating a role for the AT and
p53 genes respectively in this process. In contrast to wild-type
normal fibroblast cell strains, the G1-block in all tumor cell
lines was significantly reduced, irrespective of their p53
status. None of the nine human tumor cell lines with mutant p53
genes showed a significant G1-block following irradiation with 4
Gy. Among the five tumor cell lines expressing wild-type p53, two
showed no apparent G1-block. The remaining three showed a
G1-block involving only 8-15% of the cell population, a block
much smaller in magnitude than that seen in diploid fibroblasts.
Finally, a diploid fibroblast cell strain and a tumor cell line,
both showing a normal p53 and p21/WAF1 expression pattern, were
examined for pRb phosphorylation before and after irradiation.
The diploid fibroblast cell strain showed a significant G1-arrest
and a clear inhibition of pRb phosphorylation by irradiation
whereas the tumor cells showed no G1-arrest and no inhibition of
pRb phosphorylation. These results suggest that (1) multiple
genetic factors may modulate the occurrence and magnitude of the
G1-arrest induced by exposure to ionizing radiation, (2) the
capacity for p53 to mediate a radiation-induced G1 arrest is
significantly reduced in tumor cells, (3) the disruption of
G1-block modulating factor(s) other than p53 may be an important
step in carcinogenesis.


Takasaki M; Konoshima T; Kozuka M; Tokuda H

Anti-tumor-promoting activities of euglobals from Eucalyptus

Kyoto Pharmaceutical University, Japan.

Source: Biol Pharm Bull 1995 Mar;18(3):435-8

Unique Identifier: 96031325


To search for possible anti-tumor-promoters (chemopreventive
agents), we carried out a primary screening of 21 euglobals
(acylphloroglucinol-monoterpene or -sesquiterpene structures)
isolated from the juvenile leaves of five species of Eucalyptus
plants using an in vitro synergistic assay system. Of these
compounds, euglobal-G1--G5 (1-5), -Am-2 (15) and -III (16)
exhibited significant inhibitory effects on Epstein-Barr virus
(EBV) activation induced by the tumor promoter,
12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the
effects of compounds 1 and 16 on the cell cycle of Raji cells
were also examined by a flow cytometer, and both compounds 1 and
16 exhibited strong inhibition on the effect of the cell cycle
induced by TPA. These two euglobals (1 and 16) exhibited
remarkable anti-tumor-promoting effects on mouse skin tumor
promotion in an in vivo two-stage carcinogenesis test.


Nakamura T; Ide H; Eguchi R; Hayashi K; Hanyu F; Nagasako K; Yukawa M; Asaka K; Fujimori T; Maeda S

Expression of p53 protein related to human papillomavirus and DNA
ploidy in superficial esophageal carcinoma.

Department of Surgery, Tokyo Women's Medical College, Japan.

Source: Surg Today 1995;25(7):591-7

Unique Identifier: 96053993


We examined the p53 protein and human papilloma virus (HPV) by
immunohistochemistry and DNA ploidy by cytofluorometry in
paraffin-embedded esophageal carcinoma tissue specimens.
Sixty-one patients with superficial esophageal carcinoma were
operated on between 1983 and 1991 without any prior treatment.
Immunostaining of the anti-p53 protein antibody (CM1) was
positive in 32 carcinomas (52%). Patients with p53-positive
tumors had a poorer outcome than those with p53-negative tumors
(P < 0.05). In addition, patients with p53-positive tumors did
not have any characteristic site of relapse. Only 5 of the 61
patients (8.2%) had HPV-positive tumors. One of these 5
carcinomas expressed both p53 protein and HPV. Three patients
with HPV-positive tumors which had invaded the submucosal layer
died of relapse. A determination of DNA ploidy revealed 30
patients with aneuploid tumors, 13 with polyploid tumors and 18
with diploid tumors. The outcome of the patients with aneuploid
tumors was worse than that of the patients with diploid tumor (P
< 0.05). p53 protein expression was not associated with DNA
ploidy; however, the 16 patients who had both p53-positive and
aneuploid tumors had a worse prognosis than patients with
p53-negative and aneuploid tumors (P < 0.01). These findings
suggest that p53 protein expression in conjunction with DNA
ploidy may be a useful indicator in evaluating the prognosis of
patients with superficial esophageal carcinoma.


Dagadin GIu

Severe complication after removal of scars and papilloma of the
larynx with YAG-Nd laser

Source: Vestn Otorinolaringol 1995 Jul-Aug;(4):50

Unique Identifier: 95407027

[No abstract available]


Hudock J; Hanau CA; Hawthorne C; Jordan AG

Predictors of human papilloma virus in patients with

Department of Pathology and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.

Source: Diagn Cytopathol 1995 Feb;12(1):28-31

Unique Identifier: 95309092


Given the prevalence of human papilloma virus (HPV) infection, an
attempt was made to determine whether certain factors such as
keratinization and/or squamous atypia are associated with its
development. Review of our gynecologic cytology files from 1989
yielded 1,615 specimens showing parakeratosis and/or
hyperkeratosis, without cytologic evidence of HPV. Concomitant
diagnoses included no atypia [keratinization only (KO)],
inflammatory squamous atypia (ISA), and squamous atypia (SA).
Morphologic follow-up including repeat cytology or biopsy was
available for 916 cases, 92 (10.0%) of which possessed changes of
HPV. For any case with both cytologic and biopsy evidence of HPV,
only the biopsy result was tabulated. HPV on follow-up
examination was detected in 52 (6.7%) of the 764 cases with KO;
in 20 (20.8%) of the 96 cases with keratinization and ISA (KISA);
and in 20 (35.7%) of the 56 cases with keratinization and SA
(KSA). The definitive diagnosis of HPV was based on previously
described features (Gupta, In: Comprehensive Cytopathology,
Philadelphia: WB Saunders, 1991:133-140) including nuclear
enlargement with nuclear membrane irregularities in combination
with sharply demarcated paranuclear cytoplasmic clearing.
Affected cells have rounded borders. Binucleated cells are not
uncommon. The increasing percentage of HPV from KO to KISA to KSA
is not necessarily surprising. However, mathematical analysis
revealed statistically significant differences in the development
of HPV in each of the 3 groups: KISA vs. KO (P < 0.001), KSA vs.
KO (P < 0.001), and KSA vs. KISA (P < 0.05). Therefore, a
cytologic diagnosis of keratinization with ISA or especially SA
should warrant closer follow-up than that of KO.


McCarthy MJ; Rosado-de-Christenson ML

Tumors of the trachea.

Department of Radiology, University of Texas Health Science Center San Antonio 78284-7800, USA.

Source: J Thorac Imaging 1995 Summer;10(3):180-98

Unique Identifier: 95404750


Tumors of the trachea are rare and create signs and symptoms that
mimic common upper airway diseases. A tracheal mass is not
usually considered in the clinical differential diagnosis of an
affected patient and is often overlooked on chest radiographs.
The purpose of this article is to prompt earlier diagnosis and
improve long-term survival of patients with a tracheal tumor
through the presentation of the salient clinical, pathological,
and radiological features of a variety of benign and malignant
tracheal diseases.


Chen LC; Tarone R; Huynh M; De Luca LM

High dietary retinoic acid inhibits tumor promotion and malignant
conversion in a two-stage skin carcinogenesis protocol using
7,12-dimethylbenz[a]anthracene as the initiator and mezerein as
the tumor promoter in female SENCAR mice.

Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892, USA.

Source: Cancer Lett 1995 Aug 16;95(1-2):113-8

Unique Identifier: 95384977


We studied the effect of dietary retinoic acid (RA) in a
two-stage protocol of skin carcinogenesis in female SENCAR mice.
At 3 weeks of age mice were initiated with
7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and promoted
with either 12-O-tetradecanoylphorbol-13-acetate (TPA, 2
micrograms) once per week or mezerein (MEZ, 4 micrograms) twice
per week for 20 weeks. At the week of DMBA initiation mice were
also put on a purified diet containing either 3 (physiological
dose) or 30 micrograms (pharmacological dose) of RA/g of diet.
High dietary RA significantly inhibited papilloma yield but not
incidence in the MEZ-promoted group. Papilloma incidence and
yield were also lower in the MEZ- than in the TPA-treated groups.
Cumulative carcinoma incidence and yield, and conversion
efficiency (= (carcinomas/maximal papillomas) x 100%), were all
decreased by high dietary RA in both MEZ- and TPA-treated groups.
These results demonstrate that high dietary RA inhibited skin
carcinogenesis in MEZ-promoted mice at the stages of tumor
promotion and malignant conversion, while this inhibition
occurred only at the malignant conversion stage in TPA-promoted


Eike A; Buchwald C; Rolighed J; Lindeberg H

Human papillomavirus (HPV) is rarely present in normal oral and
nasal mucosa.

Department of Audiology, Aarhus Kommunehospital, Denmark.

Source: Clin Otolaryngol 1995 Apr;20(2):171-3

Unique Identifier: 95361209


The association between human papillomavirus (HPV) and cervical
carcinomas is well known. HPV has been found in oral carcinomas
and paranasal papillomas, and the question of a causal role of
HPV has yet to be answered. Reports on the frequency of HPV in
oral and paranasal sinus tumours should be considered in relation
to the frequency of HPV in normal oral and nasal mucosa. In the
present study 61 normal individual had oral smears taken and 48
had nasal smears. These were examined for HPV by DNA
amplification with HPV consensus primers. HPV was not found in
the oral mucosa, while a single individual harboured HPV in the
nasal mucosa. It is concluded that HPV is rarely present in
normal oral and nasal mucosa.


Shillitoe EJ; Kamath P; Chen Z

Papillomaviruses as targets for cancer gene therapy.

Department of Microbiology and Immunology, SUNY College of Medicine, Syracuse 13210, USA.

Source: Cancer Gene Ther 1994 Sep;1(3):193-204

Unique Identifier: 95346701


Gene therapy of human cancer is likely to be most effective when
it is directed at targets that are expressed in cancer cells but
are lacking from other cells. Human papillomaviruses can provide
such targets, since these viruses are present in many cervical
and oral cancers, and are likely to be etiological agents of the
tumor. Continued expression of human papillomavirus genes is
probably necessary for the growth of these cancers, and effective
gene therapy could consist of antisense or ribozyme molecules
directed against these genes. Some human papillomavirus gene
products are antigenic, and immunotherapy based upon these
antigens might prove clinically beneficial. Human
papillomaviruses have specific promoters, are linked to toxin
genes, the toxin may be selectively expressed by tumor cells
where the virus genes are active. Thus, there are several
approaches for the development of specific gene therapy for human
cancers that contain human papillomaviruses.


Harries ML; Juman S; Bailey CM

Recurrent respiratory papillomatosis in the larynx: re-emergence
of clinical disease following surgery.

Department of Paediatric Otorhinolaryngology, Hospital for Children, London, UK.

Source: Int J Pediatr Otorhinolaryngol 1995 Mar;31(2-3):259-62

Unique Identifier: 95301395


The treatment and aetiology of recurrent respiratory
papillomatosis remains unclear. We report a case of laryngeal
papillomatosis where repeated suction diathermy and later laser
treatment led to the formation of a substantial glottic web, but
a clinically papilloma-free state of the upper aerodigestive
system. Division of the web led to widespread recurrence of the
papillomas, which eventually resolved after the larynx had healed
with the reformation of a limited anterior web. The role of
surgical trauma and its effect on re-emergence of papillomas is


Shah H; Garbe L; Nussbaum E; Dumon JF; Chiodera PL; Cavaliere S

Benign tumors of the tracheobronchial tree. Endoscopic
characteristics and role of laser resection.

Respiratory Services, Kettering Medical Center, Dayton, Ohio, USA.

Source: Chest 1995 Jun;107(6):1744-51

Unique Identifier: 95300540


We conducted a review of all the bronchoscopies performed at our
institutions for benign tumors from 1980 to 1991 to determine the
endoscopic characteristics of these lesions. We reviewed the
charts, the endoscopic characteristics from our video records,
and finally the pathologic findings of these cases. We tried to
identify the effectiveness of laser resections in each group. Of
a total of 3,937 patients, 185 (4.7%) were benign tumors. On
these patients, 317 procedures were carried out. There were 3
myoblastomas, 53 papillomas, 1 adenoma, 8 chondromas, 4 fibromas,
45 hamartomas, 15 hamartochondromas, 6 lipomas, 19 angiomas, 5
leiomyomas, 4 schwannomas, 1 neurofibroma, and 21 amyloidomas.
Results of laser resection were very good in 115 (62%) and
good in 70 (38%). Complications were minimal: two mediastinal
emphysemas, one pneumothorax, and one anesthesia-related cardiac
arrest leading to the single death in this series. In general,
benign tumors of the proximal endobronchial tree responded well
to laser resection when their endoscopic appearance is recognized
and prognosis known. Even when recurrent, repeated procedures can
be performed easily with good results. This series is probably
the largest in the world's literature about endoscopic
recognition and the role of laser resection in patients
presenting with benign endobronchial tumors.


Steinberg BM

Role of human papillomaviruses in benign and malignant lesions.

Division of Otolaryngologic Research, New Hyde Park, NY, USA.

Source: Cancer Treat Res 1995;74:1-16

Unique Identifier: 95298560

[No abstract available]


Andrews SE

Laser ablation of recurrent laryngeal papillomas in children.

Winn Army Community Hospital, Fort Stewart, Ga, USA.

Source: AORN J 1995 Mar;61(3):532-40, 543-4

Unique Identifier: 95297836


Papillomas are the most common laryngeal tumors in childhood, and
their etiology is thought to be viral. Papillomatosis (ie,
widespread, multiple papillomas) may involve a child's airway
from the epiglottis to the bronchi. Hoarseness is an early sign
of juvenile laryngeal papillomas (JLP), and airway obstruction is
a later, life-threatening sign. The recurrence and spread of JLP
is common. An otorhinolaryngologist may perform a tracheostomy on
a child with JLP; however, this procedure is avoided if possible,
because a tracheostomy predisposes the trachea to papilloma
seeding. Laser ablation of papillomas through the use of rigid
endoscopic equipment and a carbon dioxide laser is the mainstay
of therapy.

Niccoli V; Serrao L

Human papillomavirus infections in pregnancy

Istituto di I Clinica Ostetrica e Ginecologica, Universita degli Studi di Roma La Sapienza.

Source: Clin Ter 1994 Oct;145(10):319-24

Unique Identifier: 95120962


After an overview on the diffusion and transmission of the Human
Papilloma Virus infection, the authors' attention is focused on
clinical and therapeutic aspects of the disease. Following the
most recent findings on congenital transmission, problems related
to prophylaxis and therapy are discussed.


Van Cutsem E; Snoeck R; Van Ranst M; Fiten P; Opdenakker G; Geboes K; Janssens J; Rutgeerts P; Vantrappen G; de Clercq E

Successful treatment of a squamous papilloma of the
hypopharynx-esophagus by local injections of

Department of Gastroenterology, Katholieke Universiteit Leuven, Belgium.

Source: J Med Virol 1995 Feb;45(2):230-5

Unique Identifier: 95294546


Human papillomaviruses (HPV) are associated with benign lesions
and show specificity towards the location or tissues that they
infect. HPVs are responsible for warts. Among more than 60
different HPV types known to occur in humans, a strong
association has been found between types 16 and 18 and cervical
cancer, and such an association is also suspected for types 31,
33, 35, 45, 51, 52, and 56. We describe the effects of
(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine (HPMPC),
following local intratumoral injection, in a 69-year-old woman
with hypopharyngeal and esophageal papillomatous lesions,
polymerase chain reaction (PCR) positive for HPV types 16 and 18,
that relapsed after surgery and that also failed to respond to
Nd-Yag laser photocoagulation and alpha-interferon treatment (6 x
10(6) U five times a week for 4 weeks followed by three times a
week for 2 months). HPMPC was given at 1.25 mg/kg, with a
sclerosing needle, through the biopsy channel of a
video-endoscope, directly into the tumor, from March until July
1993 at seven different occasions. The first four injections were
given at an interval of 1 week at the level of the hypopharynx.
The next three injections were given at an interval of 3 to 5
weeks. During the fourth to the seventh session, half of the dose
was injected into the hypopharyngeal and the other half into the
esophageal tumor. Three further injections of HPMPC were
administered at the level of the esophageal tumor in September
1993 with 2-week intervals. After HPMPC treatment, the lesions
became smaller and flat until they completely disappeared. (Abstract truncated)

Lipford GB; Bauer S; Wagner H; Heeg K

Peptide engineering allows cytotoxic T-cell vaccination against
human papilloma virus tumour antigen, E6.

Institute for Medical Microbiology, Technical University of Munich, Germany.

Source: Immunology 1995 Feb;84(2):298-303

Unique Identifier: 95270280


Major histocompatibility complex (MHC) class I allele-specific
binding motifs have proved useful in predicting cytotoxic T-cell
epitopes from immunogenic proteins. In a search of the E6 protein
from human papilloma virus type 16 utilizing the Kb binding
motif, we discovered four potential binding peptides. One
peptide, E6.1 (sequence 50-57, YDFAFRDL), was poor in its ability
to stabilize empty Kb on RMA-S cells, with a t1/2 = 33 min versus
30 min for empty Kb. This peptide subsequently proved to be
non-immunogenic upon mouse in vivo vaccination. It was
hypothesized that an isoleucine for aspartate substitution at
position 2 would improve Kb stabilization kinetics and therefore
immunogenic potential. The engineered peptide E6.1 I2 increased
the Kb t1/2 to 100 min and was immunogenic upon in vivo
vaccination. Cytolytic T lymphocytes (CTL) raised with the E6.1
I2 peptide responded to cells pulsed with either the wild-type
peptide or the engineered peptide, implying a blindness to the
substitution. More striking, these CTL also lysed a syngeneic
cell line transfected with the E6 gene, implying that the E6.1
peptide was processed and presented. These data demonstrate that
subimmunogenic peptides can be engineered to improve binding
kinetics, which in turn improves immunogenicity. Provided that
poor binding peptides are processed, the induction threshold for
CTL activation can be achieved with engineered peptides, thus
allowing for the kill of wild-type target cells. This approach
may prove relevant to the design of subunit vaccines to virally
induced tumours.


Furstenberger G; Kopp-Schneider A

Malignant progression of papillomas induced by the
initiation--promotion protocol in NMRI mouse skin.

Research Programs Tumor Cell Regulation, German Cancer Research Center, Heidelberg.

Source: Carcinogenesis 1995 Jan;16(1):61-9

Unique Identifier: 95136421


Recording of individual responses to initiation-promotion was
used to study the relationship between papilloma and carcinoma
formation in NMRI mouse skin. This type of analysis is without
precedent in that it allows a statistical evaluation of the data
which was impossible with previously published analyses based
upon cumulative tumor response data evaluated in other mouse
strains. Initiation with DMBA and promotion with TPA yielded
papillomas consisting of two sub-populations, reversible and
persistent papillomas. The ratio of persisting to reversible
papillomas was independent of the duration of promotion,
indicating comparable growth rates for both types of papillomas.
Fifty percent of the persistent and 4% of all papillomas
progressed into carcinomas. Promotion for > 20 weeks increased
neither the total number of papillomas nor the number of
carcinomas. Both the maximum number of persistent and the maximum
number of reversible papillomas correlated with the risk of
malignant progression, excluding persistent papillomas as being
the exclusive precursor lesions for malignant progression.



Immunology of the human papilloma virus in relation to cancer.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.

Source: Curr Opin Immunol 1994 Oct;6(5):746-54

Unique Identifier: 95127113


Human papillomaviruses (HPVs) have been associated with benign
and malignant epithelial proliferations in either skin or mucosa.
Two HPV oncogenic proteins, E6 and E7, are important in the
induction and maintenance of cellular transformation and are
co-expressed in the majority of HPV-containing carcinomas.
Therefore, vaccines targeted to these proteins may provide an
opportunity to prevent and treat HPV-associated malignancies. The
encouraging results from recent experimental vaccination systems
in animal models suggest that continued exploration in these
systems might lead to trials on human subjects and might allow us
to prevent HPV infection or control its potentially
life-threatening consequences.


Katial RK; Ranlett R; Whitlock WL

Human papilloma virus associated with solitary squamous papilloma
complicated by bronchiectasis and bronchial stenosis.

Department of Medicine, Dwight David Eisenhower Army Medical Center, Augusta, Ga 30905-5650.

Source: Chest 1994 Dec;106(6):1887-9

Unique Identifier: 95079832


A 28-year-old man presented with recurrent pneumonias for 6
years. Chest radiograph and computed tomography showed localized
bronchiectasis of the anterior segment of the left upper lobe.
Bronchoscopy showed bronchial stenosis without an endobronchial
lesion. After 6 weeks of antibiotic treatment, the patient had a
recurrent pneumonia and underwent left upper lobectomy that
showed a solitary squamous papilloma. In situ hybridization
studies of the papilloma were reactive for human papilloma virus
subtypes 6/11.


Birt DF; Pelling JC; Anderson J; Barnett T

Consumption of reduced-energy/low-fat diet or
constant-energy/high-fat diet during mezerein treatment inhibited
mouse skin tumor promotion.

Eppley Institute for Research in Cancer and Allied Diseases, Department of Biochemistry and Molecular Biology, Universit

Source: Carcinogenesis 1994 Oct;15(10):2341-5

Unique Identifier: 95043045


Previous studies in our laboratory have shown that promotion of
two-stage skin carcinogenesis in the SENCAR mouse model was
inhibited in mice fed energy-restricted/low-fat diets, and
elevated in mice fed high-fat diets. Studies reported here
describe the influence of dietary energy restriction from fat and
carbohydrate (ER) or high-fat (HF) diet on early promotion by
12-O-tetradecanoylphorbol-13-acetate (TPA) and on late promotion
by mezerein (MEZ). Female SENCAR mice were initiated topically
with 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA) in 0.2 ml
acetone at 9 weeks of age. For the following 2 weeks they
received 3.2 nmol TPA in 0.2 ml acetone twice weekly, and for the
next 16 weeks they received 10 nmol MEZ in 0.2 ml acetone twice
weekly. All mice were fed control diet before TPA began and
following the final MEZ treatment. Control mice received the
control diet (c) throughout TPA and MEZ (C/C). The six
experimental groups received: (1) ER diet throughout TPA and MEZ
treatment (ER/ER); (2) HF diet throughout TPA and MEZ treatment
(HF/HF); (3) ER during TPA (ER/C); (4) ER during MEZ (C/ER); (5)
HF diet during TPA (HF/C); or (6) HF diet during MEZ (C/HF).
Papilloma incidence and multiplicity, and carcinoma incidence
were similarly reduced in the mice fed ER diet during MEZ (ER/ER
and C/ER groups). In comparing the HF groups, papilloma
multiplicity was highest in the HF/C group, intermediate in the
C/C and lowest in the C/HF groups, but papilloma and carcinoma
incidences were not modified by the HF diet protocols. Papilloma
regression was greater in the C/HF group (27%, 4 regressions/15
tumor-bearing mice) than in the controls (0/18) during weeks
21-23, immediately following the end of MEZ treatment (P < 0.05).



Singh B; Ramsaroop R

Clinical features of malignant transformation in benign laryngeal

Department of Otolaryngology, University of Natal, South Africa.

Source: J Laryngol Otol 1994 Aug;108(8):642-8

Unique Identifier: 95016254


Laryngeal papillomata can undergo spontaneous malignant
transformation without being detected histologically and, in some
instances, the disease may become so advanced, before the
diagnosis is confirmed, that it is beyond any form of curative
treatment. Because of this limitation imposed by
histopathological investigation, a study was undertaken in 17
adults with benign laryngeal papillomata, (three of whom
underwent malignant transformation) to determine whether
malignant transformation can be predicted from the clinical
behaviour of the tumour. The following features were analysed:
age, sex, patient's symptoms, frequency of excision of the
papillomata, site of lesion, presence or absence of laryngeal
oedema, the need for tracheostomy, vocal fold mobility and
presence or absence of cervical lymph nodes. It was found that
decreased vocal fold mobility, the presence of cervical lymph
nodes, exuberant and rapid growth requiring very frequent
excisions, oedema of the larynx with airway obstruction requiring
a tracheostomy are clinical features suggestive of malignant


Nunez DA; West K; Wells M

Human papilloma viruses in the human hypopharynx.

Otolaryngology Department, Leicester Royal Infirmary, UK.

Source: Clin Otolaryngol 1994 Jun;19(3):258-60

Unique Identifier: 95008307


The possible association of human papilloma viruses (HPV) with
laryngopharyngeal squamous cell carcinoma is under investigation.
Recent work suggests regional differences in the prevalence of
HPV infection in the hypopharynx. The present study investigates
the prevalence of HPV in tissue obtained from a series of
piriform fossae. Piriform fossa epithelium was harvested from 12
autopsy cases free of local disease. DNA was obtained by
SDS/Proteinase K digestion. Evidence of HPV infection was
documented by the polymerase chain reaction using oligonucleotide
primers complementary to sequences in the E6 region of HPV types
11, 16 and 18. All the specimens were positive for beta-globin.
HPV11 was isolated from two patients. None were positive for
HPV16 or HPV18. An 18% prevalence rate for HPV11 in the normal
human hypopharynx was found.

Wilde E; Duggan MA; Field SK

Bronchogenic squamous cell carcinoma complicating localized
recurrent respiratory papillomatosis.

Foothills Hospital, Calgary, Alberta, Canada.

Source: Chest 1994 Jun;105(6):1887-8

Unique Identifier: 94265570


Bronchogenic squamous cell carcinoma has been reported in
patients with recurrent respiratory papillomatosis (RRP)
extending into the tracheobronchial tree even in the absence of a
history of radiation therapy or smoking. We present a case of
bronchogenic squamous cell carcinoma developing in a patient with
RRP localized to the larynx for 45 years.


Lippman SM; Donovan DT; Frankenthaler RA; Weber RS; Earley CL; Hong WK; Goepfert H

13-Cis-retinoic acid plus interferon-alpha 2a in recurrent
respiratory papillomatosis.

Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.

Source: J Natl Cancer Inst 1994 Jun 1;86(11):859-61

Unique Identifier: 94238712

[No abstract available]


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