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Biomedical subjects

P Rady

Publications and source records attributed to P Rady.

14 recordsLinked to original sources
PubMed1995

Effect of interferon therapy on human papillomavirus copy number in patients with Condyloma acuminatum.

Interferons exert antiviral, antiproliferative, and immunomodulatory effects on target cells. The effectiveness of interferon treatment can be followed by measuring parameters involved in interferon action. The clinical effectiveness of interferons has been proved in the human papillomavirus (HPV)-associated disease condyloma acuminatum. Because one of the most important goals in the treatment of this condition is the elimination of recurrences, it was asked whether clinically effective interferon therapy was associated with elimination of HPV DNA. The authors used a polymerase chain reaction-based method to detect the HPV from minute amounts of clinical biopsies. Human papillomavirus-transformed cell lines or cloned HPV genomes served as different copy number controls. The intensity ratio of L1 HPV and the human beta-globin (which served as an internal control) fragments was determined and used for estimation of HPV copy number in different biopsies. A direct effect of interferon treatment on HPV viral genome copies was observed in a group of responder patients, but not in the clinically resistant group. With these data, a correlation was found between virologic data and clinical findings. This method also can be used in other lesions to determine the HPV copy number and HPV type and may have value in determining the antiviral activities of other agents used in the treatment of HPV-related lesions.

Cell Line↗
PubMed1995

Development of human papillomavirus type 16 associated squamous cell carcinoma of the scrotum in a patient with Darier's disease treated with systemic isotretinoin.

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Darier's disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies.

Amino Acid Sequence↗
PubMed1994

Interferon treatment enhances the expression of underphosphorylated (biologically-active) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Interferons (IFN) regulate transcription of certain genes playing a role in cell proliferation. Targets of IFN action may include tumor suppressor genes such as the retinoblastoma (RB) gene and cytokines such as transforming growth factor beta 1 (TGF beta 1) and IFN beta which are inhibitors of epithelial cell proliferation. Using reverse transcription followed by PCR amplification, an increase of those growth inhibitory gene mRNA levels (TGF beta 1, IFN beta and RB) were found after interferon treatment in condylomas harboring non-oncogenic human papilloma virus (HPV 6/11) types, in an oncogenic HPV 16-containing cell line, and in a HPV negative, epidermoid carcinoma cell line. In addition, immunodetection by Western blot demonstrated a higher proportion of underphosphorylated (active form) retinoblastoma gene protein (pRB) after IFN treatment due to the decrease in the phosphorylating cdc2 kinase levels. Changes in the phosphorylation pattern of pRB together with the increased expression of those inhibitory genes represent a growth inhibited state in those cells as demonstrated by diminished c-myc expression. Since the extent of c-myc inhibition was significantly lower in the case of oncogenic HPV infection, a role of viral oncoproteins in abrogation of the antiproliferative effect of IFN therapy could be considered. These results demonstrate a new mechanism via which IFNs exert their antiproliferative effect on HPV-infected cells by affecting the expression and phosphorylation of the RB tumor suppressor gene, through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Blotting, Western↗
PubMed1994

Analysis of multiple molecular changes in human endocrine tumours.

To define the molecular changes occurring in endocrine tumours, we have analysed three human endocrine tumours established in our laboratory: BON, a functioning carcinoid tumour from the pancreas; SIM, a nonfunctioning carcinoid of the ileum; and STAN, a pheochromocytoma. A homozygous point mutation of the N-ras gene was identified at codon 61 in BON cells in conjunction with overexpression of N-ras mRNA and protein. BON cells also exhibited increased expression of c-myc and cdc2 kinase mRNA and protein; TGF-beta 1, p53 and retinoblastoma (RB) mRNA and protein levels were decreased. In addition, increased expression of the mdm2 oncogene and both the truncated and the wild-type RB protein were noted in BON. SIM cells exhibited moderately increased N-ras and c-myc mRNA levels along with decreased levels of RB mRNA and protein. Similar to BON and SIM, analysis of STAN showed increased N-ras and c-myc levels. Our data show multiple molecular changes in the three human endocrine tumours with the BON cell line exhibiting the most dramatic changes. Furthermore, our data suggest the existence of different molecular pathways in the pathogenesis of endocrine tumours. These cell lines will provide unique in vitro models to further analyse the significance of these molecular alterations.

Aged↗
PubMed1994

Alteration in the coding potential and expression of H-ras in human cytomegalovirus-transformed cells.

CMV-transformed cell lines demonstrated a greater level of H-ras RNA (7.5- to 9.5-fold) relative to the level for H-ras in parental cells. Nuclear run off assays showed that the RNA levels for the H-ras gene were regulated at the level of transcriptional initiation. The increased RNA levels for H-ras correlated with the level of p21rasVal-12 in transformed cells, while p21rasVal-12 was below the level of detection in nontransformed cells using Western blot analysis. In addition, an activating mutation was identified in both alleles of the first exon, codon 12 of H-ras resulting in a G:C to T:A transversion in all transformed cell lines examined in this study. These results suggest that the mutated H-ras may be one of the components by which an oncogenic phenotype is maintained in these CMV-transformed cells.

Base Sequence↗
PubMed1993

Benign Leydig cell tumor of the testis associated with human papillomavirus type 33 presenting with the sign of Leser-Trélat.

We present a case of a benign testicular Leydig cell tumor and eruptive seborrheic keratosis associated with human papillomavirus type 33 infection. To our knowledge this is the first occurrence of a Leydig cell tumor in a patient with tuberous sclerosis and the second documented case of eruptive seborrheic keratoses (sign of Leser-Trélat) associated with a benign neoplasm.

Adult↗
PubMed1993

Alterations in cytokine/antioncogene expression in skin lesions caused by "low-risk" types of human papillomaviruses.

Even though the "low-risk" human papillomavirus (HPV) diseases, such as condyloma acuminatum, rarely progress to malignancy, their high incidence evidences the need for a better understanding of molecular interactions between these viruses and the epithelium. Our study examined the contribution of altered expression of certain cytokines and antioncogenes to the hyperproliferative properties of HPV-related skin lesions. The "low-risk" human papillomavirus types (HPV 6 or 11) were determined by in situ hybridization and PCR amplification followed by direct sequencing using consensus primers from the highly conserved L1 region in six different condylomas. mRNA levels of certain cytokines (e.g., TGF-beta 1, IFN-beta), tumor suppressor genes (RB, p53), c-myc, epidermal growth factor receptor, and cdc2 kinase were measured by RT/PCR. A characteristic change in mRNA levels of those genes was found in condylomas compared to that of the expression levels of uninfected skin. Western blot experiments demonstrated a higher proportion of the hyperphosphorylated form of RB protein and a higher level of cdc2 kinase and c-myc, but low p53 and TGF-beta 1 levels in condylomas. These data reflect a higher proliferative state of those condylomas compared to the normal skin, suggesting a direct or indirect involvement of "low-risk" HPVs in interaction with the cellular cytokine/antioncogene system providing growth advantage to those infected cells.

Blotting, Western↗
PubMed1992

Human papillomavirus 16 exhibits a similar integration pattern in primary squamous cell carcinoma of the penis and in its metastasis.

BACKGROUND: Human papillomaviruses (HPV) are among the most common causes of sexually transmitted viral infections in the United States, and HPV types 16, 18, and others have been strongly linked with the development of cervical cancer. DNA from these oncogenic HPV types also has been detected in biopsy specimens of penile intraepithelial and invasive neoplasms, indicating a causal role of these viruses in the malignant transformation of these tissue. METHODS: Southern blot analysis and two-dimensional gel electrophoresis were used to investigate the presence and physical state of HPV in a patient with metastatic penile carcinoma. RESULTS: The presence of HPV 16 DNA integrated into the host's genome was documented in a primary penile squamous cell carcinoma and its lymph node metastasis. CONCLUSIONS: The identical restriction endonuclease cleavage patterns for HPV 16 in both the primary tumor and its lymph node metastasis indicate that both tumors arose from a single clonal event. This finding provides evidence of a causal role of HPV in squamous cell carcinoma of male genitalia.

Adult↗
PubMed1992

p53 mutations in basal cell carcinomas.

Genomic DNA from 14 basal cell carcinoma biopsies was screened for the presence of mutations in the p53 gene, using the polymerase chain reaction followed by direct DNA sequencing. Heterozygous mutations were detected in 7 of 14 (50%) samples investigated. All mutations were G:C-A:T transitions, and five (71%) of these mutations were transitions at hot spots with CpG sites, three at codon 248 and two at codon 273. The striking similarity of the type of mutations detected in this study and with the UV mutagenesis studies reported in literature suggest the hypothesis that UV may act on the p53 gene in a carcinogenic-specific fashion.

Base Sequence↗
PubMed1992

Human papillomavirus type 16 found in primary transitional cell carcinoma of the Bartholin's gland and in a lymph node metastasis.

We report a case of primary transitional cell carcinoma of the Bartholin's gland and its lymph node metastasis that contained HPV 16 sequences by polymerase chain reaction. The physical state of HPV 16 DNA in the primary cancer was investigated by Southern blot analysis which showed the presence of the episomal form of viral DNA. Our findings of HPV 16 DNA in the transitional cell carcinoma of the Bartholin's gland and its metastasis would indicate that both tumors arose from a single clonal event, thus providing evidence that the HPV 16 may have an oncogenic potential in this rare malignancy even in the episomal state.

Adult↗
PubMed1990

Morphological and immunohistochemical characteristics of dimethylnitrosamine-induced malignant mesenchymal renal tumor in F-344 rats.

Mesenchymal renal tumors in F-344 newborn rats were induced by a single dose of dimethylnitrosamine. The induced tumors were successfully transplanted into adult rats under the renal capsule. Neither the primary nor the transplanted neoplasms from various generations of grafts changed their morphological features during the tumor passage, having the same cellularity with high mitotic activity and the tendency to invade the host kidney rapidly. On the basis of lectin histochemistry and immunohistology, the tumor proved to be a mesenchymal neoplasm without any obvious capacity of the proliferating cells to differentiate into any well-known organoid element normally found in mature renal parenchyma. However, the proliferating neoplastic cells were found to have a strong vimentin positivity with desmin expression. Ultrastructurally, myofilaments with attachment bodies characteristic of smooth muscle cells were generally present in various amounts in many tumor cells. In addition, on the basis of the physiological data and on kidney/tumor renin activity obtained, it is interesting to note that the tumor-graft-invaded kidneys retained their enzyme activity, despite the obvious loss of renal tissue including glomeruli. However, the immunohistochemical findings with anti-renin antibody have clearly shown that this is not due to a renin-producing tumor but rather to the surviving (probably) non-neoplastic arterioles retaining the capacity to produce renin. Although these arterioles have mostly been found next to necrotic areas, commonly occurring in dimethylnitrosamine-induced transplantable renal tumors, the question of a possible physiological role of renin in tumor necrosis or in angiogenesis has remained open.

Animals↗