(1/994) Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas.
Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand-mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation. (+info)
(2/994) Fish oil constituent docosahexa-enoic acid selectively inhibits growth of human papillomavirus immortalized keratinocytes.
The omega-3-fatty acids inhibit proliferation of breast cancer cells whereas omega-6-fatty acids stimulate growth. In this study, we examined effects of these fatty acids on human pre-cancerous cells. Cervical keratinocytes, immortalized with the oncogenic human papillomavirus (HPV) type 16, were treated with linoleic acid, an omega-6-fatty acid, and the omega-3-fatty acids, eicosapentaenoic and docosahexaenoic acids. Using both cell counts and bromodeoxyuridine incorporation, docosahexaenoic acid inhibited growth of these cells to a greater extent than eicosapenta-enoic acid. Linoleic acid had no effect. The effect of docosahexaenoic acid was dose dependent and caused growth arrest. Docosahexaenoic acid inhibited growth of HPV16 immortalized foreskin keratinocytes and laryngeal keratinocytes grown from explants of benign tumors caused by papillomavirus, but had no effect on normal foreskin and laryngeal keratinocytes. Docosahexaenoic acid inhibited growth in the presence of estradiol, a growth stimulator for these cells. Indomethacin, a cyclooxygenase inhibitor like docosahexaenoic acid, had only minimal effect on growth. Alpha-tocopherol, a peroxidation inhibitor, abrogated effects of docosahexaenoic acid implying that inhibitory effects were via lipid peroxidation. (+info)
(3/994) Concordant induction of cyclin E and p21cip1 in differentiated keratinocytes by the human papillomavirus E7 protein inhibits cellular and viral DNA synthesis.
Productive infections by human papillomaviruses (HPVs) occur only in differentiated keratinocytes in squamous epithelia in which the HPV E7 protein reactivates the host DNA replication machinery to support viral DNA replication. In a fraction of the differentiated keratinocytes, E7 also posttranscriptionally induces p21Cip1, which is distributed in a mutually exclusive manner with unscheduled cellular DNA synthesis. In this study, double immunofluorescence labeling unexpectedly revealed that E7 caused a concordant accumulation of both cyclin E and p21Cip1 to high levels in patient papillomas and in organotypic cultures of primary human keratinocytes. The induction of cyclin E is mutually exclusive with unscheduled cellular DNA synthesis or abundant viral DNA. These novel virus-host interactions in differentiated keratinocytes are in contrast to previous observations made in submerged proliferating cultures, in which HPV E7 induces cyclin E and overcomes p21Cip1 inhibition of S-phase entry. We propose that an appropriately timed induction of cyclin E/cyclin-dependent kinase 2 by HPV E7 in postmitotic cells enables S-phase reentry and HPV DNA amplification, whereas prematurely induced cyclin E stabilizes p21Cip1 protein, which then inhibits cyclin E/cyclin-dependent kinase 2. Consequently, cyclin E and p21Cip1 both fail to turn over, and DNA synthesis does not occur. (+info)
(4/994) Benign papillary lesions of the breast: sonographic-pathologic correlation.
We reviewed the sonographic findings of 42 benign papillary lesions of the breast and correlated them with pathologic findings. Sonography detected 95% of papillomas (22 intraluminal masses, four extraductal masses, nine purely solid masses, and five mixed type masses). The sonographic margins of the mass were well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined margins on sonography were frequent in papillomas with pathologic pseudoinvasion and in juvenile papillomatosis. Most benign papillary lesions of the breast have the sonographic findings suggestive of intraductal origin. The sonographic findings of papillary lesions correlated well with pathologic findings. (+info)
(5/994) Borderline malignant change in recurrent mullerian papilloma of the vagina.
Malignant change occurred in a benign, recurrent vaginal mullerian polyp. The patient, a 49 year old woman with cerebral palsy, presented with a polypoid mass in the vagina. At four years of age she had presented with a haemorrhagic polyp, and over the following years she had recurrent irregular bleeding and regrowth of the polypoidal mass, requiring a total of 10 operations to excise the polyp. Histological examination of the specimen showed typical mullerian features with tubal, endometrioid, and endocervical cell types. There were significantly abnormal nuclei, indicating low grade or borderline malignancy. Review of previous biopsies showed similar mullerian features but no atypia. This is the first reported case of borderline malignant change in a previously benign recurrent mullerian papilloma of the vagina. Definitive radical surgery or radiotherapy is contraindicated in this patient and she remains under follow up. (+info)
(6/994) Genetic deletion of p21WAF1 enhances papilloma formation but not malignant conversion in experimental mouse skin carcinogenesis.
Tumor suppression by p53 is believed to reside in its ability to regulate gene transcription, including up-regulation of p21WAF1. In p53(-/-) mice, chemical- or oncogene-induced skin tumors undergo accelerated malignant conversion. To determine the contribution of the p21WAF1 gene product to epidermal carcinogenesis, animals +/+, +/-, and -/- for a null mutation in the p21WAF1 gene were treated once with 25 nmol 7,12-dimethylbenz[a]anthracene, followed by 5 microg of TPA two times/week for 20 weeks. Papilloma frequency was higher in the p21WAF1-deficient mice. However, the frequency of malignant conversion was similar among all three genotypes. After TPA treatment, all genotypes developed epidermal hyperplasia, although the labeling index was lower in p21WAF1 (-/-) epidermis compared with p21WAF1 (+/+). Furthermore, the expression of differentiation markers was the same across genotypes in untreated or TPA-treated epidermis. Similar frequencies of malignant conversion were also observed in an in vitro assay. Thus, p21WAF1 suppresses early stages of papilloma formation but not malignant progression in mouse skin carcinogenesis, and decreased levels of p21WAF1 do not account for the enhanced malignant conversion of p53 null epidermal tumors. (+info)
(7/994) Choroid plexus papilloma of cerebellopontine angle with extension to foramen magnum.
A case of choroid plexus papilloma resembling meningioma of cerebellopontine (CP) angle with its extension to foramen magnum is presented. Occurrence of this tumour in CP angle is very rare. Its extension towards foramen magnum is further rare. It was a real diagnostic enigma preoperatively as the tumour was resembling meningioma upto some extent on radiological study. Retromastoid craniectomy with microsurgical excision of tumour and its extension was achieved in toto. Tumour was attached to few rootlets of lower cranial nerves which were preserved. Attachment of the tumour with lower cranial nerves again caused diagnostic confusion with neurofibroma intraoperatively. (+info)
(8/994) Nitrogen intake and tumorigenesis in rats injected with 1,2-dimethylhydrazine.
Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic casein-sucorse deits containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numberous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol reose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Altough the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks. (+info)