Large Papillomas Research Articles

Importance of Cryotherapy for Eyelid Papillomas

Cryotherapy as a destructive procedure is an important alternative to the surgical excision of eyelid tumors. We report our own experiences in the cryotherapy of large upper eyelid papillomas using spray- and contact-freezing. Cryotherapy gave excellent results in the treatment of unusually large papillomas. The preservation of collagen structures during cryotherapy provides a good aesthetic and functional outcome.

Clinical, histopathological and histochemical characterization of cutaneous papillomatosis in bovine (Bos taurus) of Córdoba department, Colombia

The objective of this study was to study the clinical, histopathological and histochemical aspects of cutaneous papillomatosis (CP) in cattle (Bos taurus) of the department of Cordoba, Colombia. This study was descriptive, not probabilistic, in animals of convenience. Were used Twenty - four bovines with BCP diagnosed clinically and histopathologically. In describing the lesions exophytic and hyperpigmented masses were observed in some cases, pedicled or in the form of cauliflower in others and even in the flat papillomas showed the pedicles to the compression. Similarly, large pendulum papillomas were surgically removed, which when dissected revealed epithelial hyperplasia, hyperkeratosis and the projection of the epidermis to the dermis. At head level, the largest presentation was given in mouth, ears, forehead and eyelids. Histopathologically in the H-E staining, were observed epithelial hyperplasia, acanthosis, digital projections to the dermis and hyperkeratosis. In the T-G staining, marked dermal proliferation of disorganized collagen with little diffuse connective tissue was present, and in the P-R / P staining, marked areas of reddish birefringence and scarce birefringence were observed. The definitive diagnosis of the disease was based on the clinical characteristics, differential diagnosis and histopathological findings, being conclusive as diagnostic methods for CP in bovines in the Department of Cordoba.

IN VIVO INVESTIGATION OF BOVINE CUTANEOUS PAPILLOMATOSIS WITH HOMEOPATHIC PREPARATIONS

This investigation was carried out to determine the effects of thuza and antim crud (Homeopathic preparations) on bovine cutaneous papillomatosis/wart. Nine calves of one to two and a half years age and of both sexes affected with cutaneous papillomatosis were randomly divided into three equal groups (group I, group II and group III) for this experiment from March 2002 to February 2003. Each calf of group I was first administered with 15 globules sulphur with a potency of 200-power once orally. This was followed after 7 days with 50M (M = 1000-power) thuza at the dose rate of 10 globules twice daily orally for a period of three weeks. The calves of group II were administered with sulphur and antim crud at the same dose, potency, route and duration, respectively and the calves of group III were kept as untreated control. Papilloma tissues were collected prior to treatment and at the sixth week of treatment and they were subjected to histopathological examination. Thuza and antim crud with concurrent use of sulphur were found effective in curing bovine cutaneous papillomatosis with a rate of 66.66% (4/6). Little or no reduction in size of the papillomas was observed within the first two weeks of treatment in both the treated groups (group I and group II). Thereafter, miniature size sessile and pedunculated papillomas started drying with the gradual reduction in size that fell leaving hairless areas at the end of fourth week. By the eighth week there was complete cure of papillomas. One calf of each treated groups (group I and group II) affected with large papillomas (5 X 7 cm) were not completely cured. Microscopic examination of regressive papillomas at sixth week of treatment showed cellular necrosis. Growth recurrence was not observed within one month of recovery. In the untreated control group (group III), the number and size of papillomas increased. Therefore, this line of treatment may be practiced for the treatment of bovine papillomatosis.

Abstract 410: NLRP3 is involved in tumor development by regulating immune function

Abstract The NLRP3 inflammasome is a multiprotein cytoplasmic complex that mediates the processing of pro-inflammatory interleukin-1β (IL-1β), IL-18 and possibly IL-33, via the activation of Caspase-1. While NLRP3 has been widely described in the pathogenesis of inflammatory diseases, its role in tumor-host interactions, where inflammation is known to be a major player, has yet to be fully elucidated. We observed that DMBA carcinogen treatment that induced large and numerous papillomas in the skin of wt mice induced barely visible lesions in NLRP3 deficient counterparts. Similarly IV injection of B16F10 melanoma cells resulted in multiple lung metastases in wt mice but virtually no metastatic growth in NLRP3-deficient animals. The NLRP3 inflammasome thus appears to be a key helper for tumor cell growth and survival at both primary and secondary sites. Bone marrow transplantation revealed that leukocyte-derived NLRP3 plays a key role in supporting tumor cell survival prompting us to compare the immune cell distribution and function in NLRP3 deficient mice to those in wt littermates, in both the presence and absence of tumor growth. Flow cytometry analysis of immune cell populations in these mice allowed us to link NRLP3 to the recruitment, adaptation and ability of the immune system to target tumor cells. We observed that compared to wt animals, NLRP3 KO mice had fewer CD3+CD4+ T cells, NK cells and F4/80+CD11c+ myeloid cells but more CD11b+Gr1+ cells, B lymphocytes and F4/80+CD206+ macrophages of the M2 phenotype in the spleen. The increased numbers of myeloid derived suppressor cells (MDSC) and M2 macrophages in mice that displayed decreased tumor growth was counterintuitive but was associated with functional impairment that could explain decreased permissiveness of the microenvironment for tumor growth. Our observations provide a framework to investigate the mechanistic implication of NLRP3 in the relationship between tumor cells and their microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 410. doi:1538-7445.AM2012-410

Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice

Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1+/+, HO-1+/−, and HO-1−/− mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of cytoprotective genes in the livers evidenced systemic oxidative stress in the mice of all the HO-1 genotypes. Carcinogen-induced lesions appeared earlier in HO-1−/− and HO-1+/− than in wild-type animals. They also contained much higher concentrations of vascular endothelial growth factor and keratinocyte chemoattractant, but lower levels of tumor necrosis factor-α and interleukin-12. Furthermore, tumors grew much larger in HO-1 knockouts than in the other groups, which was accompanied by an increased rate of animal mortality. However, pathomorphological analysis indicated that HO-1−/− lesions were mainly large but benign papillomas. In contrast, in mice expressing HO-1, most lesions displayed dysplastic features and developed to invasive carcinoma. Thus, HO-1 may protect healthy tissues against carcinogen-induced injury, but in already growing tumors it seems to favor their progression toward more malignant forms.

Modulating Effects of Rooibos and Honeybush Herbal Teas on the Development of Esophageal Papillomas in Rats

Widespread consumption of herbal teas has stimulated interest in their role as cancer preventive agents. The present investigation monitored the modulation of methylbenzylnitrosamine (MBN)-induced esophageal squamous cell carcinogenesis by rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal and Camellia sinensis teas in male F344 rats. The tumor multiplicity was significantly (P < 0.05) inhibited by unfermented honeybush (45.5%), green (50%), and black (36%) teas, while the other teas exhibited weaker effects (<30% inhibition). The mean total papilloma size was reduced by unfermented rooibos (87%), unfermented honeybush (94%), and fermented honeybush (74%) due to the absence of large papillomas (>10 mm3). Reduction of the mean total papilloma number correlated with the total polyphenol (TPP) (r = 0.79; P < 0.02) and flavanol/proanthocyanidin (FLAVA) (r = 0.89; P < 0.008) intake (mg/100 g body weight) of the teas and the FLAVA (r = 0.89; P < 0.04) and flavonol/flavones/xanthones (r = 0.99; P < 0.002) intake when considering only the herbal teas. A daily TPP intake threshold of 7 mg/100 g body weight existed below where no inhibition of papilloma development was observed. Fermentation of herbal teas reduced the inhibitory effects on papilloma development associated with a reduction in the polyphenolic constituents. The inhibitory effect of herbal teas on papilloma development is associated with different flavonoid subgroups and/or combination thereof.

Reversal of papilloma growth in rabbits therapeutically vaccinated against E6 with naked DNA and/or vesicular stomatitis virus vectors

Persistent infection with high-risk human papillomaviruses (HPVs) is the greatest risk factor for the development of HPV-associated cancers. In this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant DNA and/or vesicular stomatitis virus (VSV) targeting the cottontail rabbit papillomavirus (CRPV) E6 protein. Immune responses were primed with either vector and boosted twice with the homologous or heterologous E6 vector. Over the course of 18 weeks, E6 vaccination reduced papilloma volumes to one third the volume in the controls, and the rabbits boosted with an heterologous vector tended to mount stronger responses. Small and medium-sized papillomas responded significantly but only slightly better than large papillomas. Finally the initial papilloma burden per rabbit, ranging from <100 mm 3 to >1000 mm 3, was not prognostic of antitumor efficacy. In summary both E6 vaccines elicited significant therapeutic immunity, and their sequential use tended to be advantageous.

Aquaporin(s) Expression in Choroid Plexus Tumours

Objective: It was the aim of this study to investigate the pattern of aquaporin 1 (AQP1) expression in normal and neoplastic choroid plexus, with specific reference to the association with communicating hydrocephalus or liquoral cysts. Second, to infer a new view on the cerebrospinal fluid plexus production and on the etiology of the cysts and communicating hydrocephalus occasionally associated with choroid plexus papillomas. Materials and Methods: Nineteen paraffin-embedded specimens, 10 of normal choroid plexus and 9 of choroid plexus tumours, were immunostained with a monoclonal antibody raised against the intracellular C-terminal AQP1 epitope. Results were analysed in terms of intensity and intracellular distribution of immunostaining and in terms of number of stained cells; they were considered in light of the clinical association with hydrocephalus or liquoral cysts. Results: AQP1 was heavily expressed in the apical side of the choroid epithelium in normal plexus specimens. Choroid plexus papillomas showed a very heterogeneous pattern of AQP1 expression. Immunostaining was absent in the case of choroid plexus carcinoma. Very strong to strong and diffuse AQP1 expression in large to very large papillomas was associated with liquoral cysts or communicating hydrocephalus. Conclusions: AQP1 expression characterizes normal choroid plexus and plexus papillomas. Intensity and diffusion of AQP1 expression together with the size of the tumour mass are somewhat predictive of communicating hydrocephalus or liquoral cyst, lesions possibly caused by a disturbance of cerebrospinal fluid homeostasis.

Is intralesional cidofovir worthwhile in juvenile recurrent respiratory papillomatosis?

To investigate the efficacy of intralesional cidofovir in the treatment of recurrent respiratory papillomatosis (RRP) in children. Prospective observational study of four consecutive children with RRP treated at an academic tertiary children's hospital. Laryngo-bronchoscopy was performed at three- to five-weekly intervals. Photodocumentation was obtained and disease severity assessed using an anatomical RRP severity score. Surgical debulking of large papillomas was then performed, and cidofovir (5 mg/ml) injected into any remaining papillomas as well as submucosally at the sites of resected papillomas. The efficacy of cidofovir was assessed by the change in papilloma severity score over the course of the treatment. Complete disease remission was obtained in one patient, with a partial response seen in two others. One patient showed no significant response. The greatest beneficial effect was seen after the fourth cidofovir injection; however, two patients demonstrated a deterioration in severity scores after treatment was withheld at this point. Both responded well to further cidofovir injections. However, a clear plateau in the response to cidofovir was seen in all patients by the eighth injection. Intralesional cidofovir may help control papilloma regrowth and reduce disease severity in many children with RRP. In most cases, cidofovir would appear to be less efficacious in causing disease eradication. There appears to be little evidence to support prolonged treatment regimes (i.e. more than eight treatments).

Knockout mice reveal a tumor suppressor function for Testin

The Testin (TES) gene was previously identified as a putative human tumor suppressor gene at 7q31.2, a region that is frequently deleted in hematopoietic malignancies, as well as in epithelial tumors. To determine whether TES acts as a tumor suppressor in vivo, we generated a Tes knockout mouse and then used it in an established model of carcinogen-induced gastric cancer. In mice a zinc-deficient (ZD) diet enhances cellular proliferation in the forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA)-induced carcinogenesis. Five-week-old Tes wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were divided into four groups: mice fed a zinc-sufficient diet (ZS); mice fed a ZD diet; ZS fed plus NMBA-treated mice (ZS+NMBA), and ZD fed plus NMBA-treated mice (ZD+NMBA). After 4 weeks, the ZS+NMBA and ZD+NMBA groups were treated with three intragastric doses of NMBA. Animals were killed 8 weeks after NMBA administration: 25% of +/+ mice developed benign lesions; 88% of +/- showed multiple papillomas, atypical glandular metaplasia, and squamous cell carcinomasl; and 81% of -/- mice displayed very large papillomas, squamous cell carcinomas, and adenocarcinomas. A statistically significant difference in tumor incidence was found between +/- versus +/+ and -/- versus +/+ (P < 0.0001). These data suggest that Tes functions as a tumor suppressor gene in vivo.

Large cutaneous rabbit papillomas that persist during cyclosporin A treatment can regress spontaneously after cessation of immunosuppression

Cottontail rabbit papillomavirus (CRPV)-induced papillomas can progress into malignant carcinomas, remain persistent or regress. Both host immunity and virus genetic background play critical roles in these events. To test how host immunity influences CRPV-induced papilloma evolution, both EIII/JC (inbred) and New Zealand White (outbred) rabbits were treated with an immunosuppressive drug, cyclosporin A (CsA), for 80 days and the regression of three regressive constructs, H.CRPVr (a CRPV regressive strain), H.CRPVp-E6r (a progressive strain with regressive E6) and H.CRPVp-CE6rm (H.CRPVp with the carboxyl terminal of regressive E6, containing mutations at amino acid residues E252G, G258D and S259P) was checked. Papillomas induced by H.CRPVr and H.CRPVp-E6r on control inbred and outbred rabbits regressed totally around week 8, whereas papillomas on all CsA-treated rabbits grew progressively. After cessation of CsA treatment, papillomas began to regress in six outbred rabbits: 14 of 18 papillomas induced by CRPVr, 11 of 18 papillomas induced by H.CRPVp-E6r and eight of 10 papillomas induced by H.CRPVp-CE6rm regressed around week 21. In four CsA-treated inbred rabbits, two of 17 papillomas induced by H.CRPVr and one of 17 papillomas induced by H.CRPVp-E6r regressed. These data indicate that papillomas induced by a regressive CRPV strain can become persistent in the transiently immunosuppressed host. However, returning immunity can lead to regression and clearance of large papillomas (with increased antigenicity) in an outbred population, whilst these same antigenic papillomas persist in inbred rabbits.

Combination treatment with intralesional cidofovir and viral-DNA vaccination cures large cottontail rabbit papillomavirus-induced papillomas and reduces recurrences.

We used the cottontail rabbit papillomavirus (CRPV) New Zealand White rabbit model to test a combination treatment of large established papillomas with intralesional cidofovir and DNA vaccination to cure sites and reduce recurrences. Intralesional 1% (wt/vol) (0.036 M) cidofovir treatment of rabbit papillomas led to elimination, or "cure," of the papillomas over a 6- to 8-week treatment period (N. D. Christenson, M. D. Pickel, L. R. Budgeon, and J. W. Kreider, Antivir. Res. 48:131-142, 2000). However, recurrences at periods from 1 to 8 weeks after treatment cessation were observed at approximately 50% of cured sites. DNA vaccinations with CRPV E1, E2, E6, and E7 were initiated either after or at the time of intralesional treatments, and the recurrence rates were observed. When DNA vaccinations were started after intralesional cures, recurrence rates were similar to those of vector-vaccinated rabbits. A small proportion of recurrent sites subsequently regressed (4 out of 10, or 40%) in the vaccinated group versus no regression of recurrences in the vector-immunized group (0 out of 19, or 0%), indicating partial effectiveness. In contrast, when DNA vaccinations were conducted during intralesional treatments, a significant reduction of recurrences (from 10 out of 19, or 53%, of sites in vector-immunized rabbits to 3 out of 20, or 15%, of sites in viral-DNA-immunized rabbits) was observed. DNA vaccination without intralesional treatments had a minimal effect on preexisting papillomas. These data indicated that treatment with a combination of antiviral compounds and specific immune stimulation may lead to long-term cures of lesions without the ensuing problem of papilloma recurrence.

In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas

A series of nucleoside analogues were tested for in vivo anti-papillomavirus activity using the cottontail rabbit papillomavirus (CRPV) domestic rabbit model. Compounds were delivered either topically, injected into growing papillomas, or delivered subcutaneously at a site remote from the papillomas. Compounds tested included cidofovir [( S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC); cyclic HPMPC (cHPMPC); cyclopentenylcytosine (CPE-C); lobucavir [1R(1α,2β,3α)]-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine; 9-((2-phosphonylmethoxy)propyl)adenine (PMPA); adefovir 9-((2-phosphonylmethoxy)ethyl)adenine(PMEA) and cyclopropyl 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (cyclopropylPMEDAP). Dose response curves and time-course treatments were included for most compounds tested. Strong anti-viral activity was detected using cidofovir and cHPMPC when delivered either topically or by the intralesional route. Complete cures were obtained using 1% (w/v) topical cidofovir at dosing schedules of twice daily for 8 weeks beginning at 4 weeks after CRPV infection, which represents a time when papillomas were clearly visible. Complete cures of large established papillomas were obtained by intralesional injection of 1% cidofovir three times per week for 8 weeks. Topical treatments with adefovir had strong anti-viral activity, cyclopropyl PMEDAP had moderate anti-viral activity, and CPE-C, PMPA and lobucavir showed no effects. These data indicate that certain nucleoside analogues have strong in vivo anti-papillomavirus activity and that the CRPV/rabbit model is a good model for assessing clinical responses of anti-viral treatments for patients with HPV disease.

Reduced expression of the CDK inhibitor p27(KIP1) in rat two-stage bladder carcinogenesis and its association with expression profiles of p21(WAF1/Cip1) and p53.

The cyclin-dependent kinase (CDK) inhibitor p27(KIP1) exerts its growth suppressive effects by targeting the cyclin-CDK complexes. Reduced protein levels of p27(KIP1) have been reported in numerous human cancers and this has been attributed to increased degradation. However, few reports have addressed the significance of p27(KIP1) expression in chemical carcinogenesis of rodents. In a rat two-stage urinary bladder carcinogenesis model, with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) initiation followed by promotion with sodium L-ascorbate (Na-AsA), we evaluated the expression of p27(KIP1) protein using immunohistochemistry during various stages of urinary bladder carcinogenesis. In addition, we evaluated the mRNA expression profiles for p27(KIP1), p21(WAF1/Cip1) and p53 in tumors. Fisher 344 rats were initiated with 0.05% BBN in the drinking water for 4 weeks and then administered 5% Na-AsA in the diet. Immunohistochemical examination revealed p27(KIP1) protein to be constitutively expressed in normal urothelium, simple hyperplasia and in most papillary and nodular (PN) hyperplasias and small papillomas, but diminished or absent in large papillomas and in transitional cell carcinomas. An inverse correlation between expression of p27(KIP1) and cell proliferation was generally observed. Quantitation of mRNA by multiplex reverse transcription-PCR showed a significant downregulaton of p27(KIP1), p21(WAF1/Cip1) and p53 mRNA in tumors. More than 50% reduction in p27(KIP1) mRNA expression was observed in 42 and 47% of tumors at weeks 18 and 24, respectively; similar reduction in p21(WAF1/Cip1) mRNA expression was observed in 58 and 73% of tumors at weeks 18 and 24, and in p53 mRNA expression in 50 and 73% of tumors at weeks 18 and 24, respectively. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis had p53 mutations. These data imply that abnormal down-regulation of p27(KIP1), p21(WAF1/Cip1) and/or p53 in tumor cells may contribute to the malignant progression of tumors during rat two-stage bladder carcinogenesis.

The Conjunctival Wart: Report of a Case and Review of Treatment Options.

Miller, D.; Brodell, R.; Levine, M.Editor(s): Arterberry, Joe F. M.D., F.A.C.S., Editor Author Information

The Conjunctival Wart: Report of a Case and Review of Treatment Options

Human papillomavirus, a papovavirus, is the causative agent of all warts. There are at least 63 subtypes of this virus, certain ones of which are more likely to cause warts in particular locations or to be associated with malignancies. Over the last 6 years, HPV-6, HPV-11, and HPV-16 have been detected in both benign and malignant lesions of the conjunctiva. We report a patient with a large viral papilloma of the palpebral conjunctiva of the right lower eyelid. This case demonstrates that even very large viral papillomas can be treated successfully.

184 In vitro metabolism and incorporation into nucleic acids of 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) in uninfected and HCMV-infected mammalian cells : M. R. Nassiri, K. Z. Borysko, L. B. Townsend and J. C. Drach. University of Michigan, Ann Arbor, MI 48109; S. S. Good, S. R. Tibbels, S. D. Gabriel and K. K. Biron, Burroughs Wellcome Co., Research Triangle Park, NC 27709

A series of nucleoside analogues were tested for in vivo anti-papillomavirus activity using the cottontail rabbit papillomavirus (CRPV) domestic rabbit model. Compounds were delivered either topically, injected into growing papillomas, or delivered subcutaneously at a site remote from the papillomas. Compounds tested included cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC); cyclic HPMPC (cHPMPC); cyclopentenylcytosine (CPE-C); lobucavir [1R(1α,2β,3α)]-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine; 9-((2-phosphonylmethoxy)propyl)adenine (PMPA); adefovir 9-((2-phosphonylmethoxy)ethyl)adenine(PMEA) and cyclopropyl 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (cyclopropylPMEDAP). Dose response curves and time-course treatments were included for most compounds tested. Strong anti-viral activity was detected using cidofovir and cHPMPC when delivered either topically or by the intralesional route. Complete cures were obtained using 1% (w/v) topical cidofovir at dosing schedules of twice daily for 8 weeks beginning at 4 weeks after CRPV infection, which represents a time when papillomas were clearly visible. Complete cures of large established papillomas were obtained by intralesional injection of 1% cidofovir three times per week for 8 weeks. Topical treatments with adefovir had strong anti-viral activity, cyclopropyl PMEDAP had moderate anti-viral activity, and CPE-C, PMPA and lobucavir showed no effects. These data indicate that certain nucleoside analogues have strong in vivo anti-papillomavirus activity and that the CRPV/rabbit model is a good model for assessing clinical responses of anti-viral treatments for patients with HPV disease.

Phosphorylation of 9-(2-phosphonomethoxyethyl)adenine and 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)adenine by AMP(dAMP) kinase from L-1210 cells : A.Merta, I.Votruba, J.Jindřich, A.Holý, T.Cihlař, I.Rosenberg, M.Otmar and H.Y.Tchaou Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, CS-166 10 Praha 6 (Czechoslovakia)

A series of nucleoside analogues were tested for in vivo anti-papillomavirus activity using the cottontail rabbit papillomavirus (CRPV) domestic rabbit model. Compounds were delivered either topically, injected into growing papillomas, or delivered subcutaneously at a site remote from the papillomas. Compounds tested included cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC); cyclic HPMPC (cHPMPC); cyclopentenylcytosine (CPE-C); lobucavir [1R(1α,2β,3α)]-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine; 9-((2-phosphonylmethoxy)propyl)adenine (PMPA); adefovir 9-((2-phosphonylmethoxy)ethyl)adenine(PMEA) and cyclopropyl 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (cyclopropylPMEDAP). Dose response curves and time-course treatments were included for most compounds tested. Strong anti-viral activity was detected using cidofovir and cHPMPC when delivered either topically or by the intralesional route. Complete cures were obtained using 1% (w/v) topical cidofovir at dosing schedules of twice daily for 8 weeks beginning at 4 weeks after CRPV infection, which represents a time when papillomas were clearly visible. Complete cures of large established papillomas were obtained by intralesional injection of 1% cidofovir three times per week for 8 weeks. Topical treatments with adefovir had strong anti-viral activity, cyclopropyl PMEDAP had moderate anti-viral activity, and CPE-C, PMPA and lobucavir showed no effects. These data indicate that certain nucleoside analogues have strong in vivo anti-papillomavirus activity and that the CRPV/rabbit model is a good model for assessing clinical responses of anti-viral treatments for patients with HPV disease.

Promoting Effect of Sodium Chloride Solution Mist on the Induction of Papillomas on Syrian Hamster Tracheal Mucosa Following Administration of Diethylnitrosamine

The promoting effect of NaCI solution mist was studied in the induction of papillomas on Syrian hamster trachea following single subcutaneous injection of diethylnitrosamine (DEN). Sixty male hamsters were divided into three groups. Group A; Exposure to a 5% NaCl solution mist for 32 weeks following single subcutaneous injection of DEN at a dose of 3 mg/100 g body weight. Group B; Subcutaneous DEN injection alone. Group C; Exposure to the NaCI mist for 32 weeks alone. Total numbers of papillomas on the trachea in each group were 107 in group A, 64 in group B, and 0 in group C (P0.05 between group A and B, P<0.01 between either groups A or B and C). Comparing the incidence of large papillomas with a diameter of more than 2 mm, that in group A hamsters was significantly greater than that of group B (22 large papillomas vs. 8 large papillomas, P<0.01). No difference in the effects on the epithelial cells of the nasal cavity, the bronchial or the alveolar cells in the lung was recognized between groups A and B. The hamsters in group C were not observed to have any changes in any of the respiratory organs. Inhalation of NaCI solution mist is considered to have a promoting effect on the induction of papillomas in the hamster trachea following DEN injection.

Hematoporphyrin derivative therapy of papillomas. Experimental study.

Hematoporphyrin derivative has been shown to selectively localize in malignant tissues and chemically induced animal papillomas. It is a powerful photo-sensitizing agent that can cause destruction and death of tissues in which it has localized by the generation of singlet oxygen when activated by light of the appropriate wavelength (photodynamic therapy [PDT]). Laryngeal papillomas are rapidly growing benign epithelial neoplasms with a clinical course marked by multiple recurrences after surgical removal. Before considering PDT as a therapeutic modality in the treatment of this debilitating disease we developed an animal model for experimentation. Using the cottontail rabbit papillomavirus, sometimes referred to as the Shope papillomavirus, large cutaneous papillomas were induced on the backs of Dutch Belted rabbits. Following intravenous administration of hematoporphyrin derivative, PDT was delivered with white light. Marked regression of the papillomas was noted with replacement by normal hair-bearing skin. The clinical implications of this work to the control of laryngeal papillomatosis is discussed.