RRP Medical Reference Service
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
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:
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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 mice.
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 papillomavirus.
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 antigen.
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 pathology.
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 steroid.
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.
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 plants.
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.
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 keratinization.
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 mice.
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 discussed.
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.
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]
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 (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.
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 papillomata.
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 transformation.
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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