The kinetics of the tanning response to tanning bed exposures

No clinical studies have been published documenting the development of pigmentation following the use of the Food and Drug Administration (FDA) recommended exposures from a tanning bed. Panelists were exposed three times weekly for eight weeks (24 exposures) using the FDA recommended exposure schedule. The initial tan was noted after only six exposures and quantitatively increased through the remainder of the study.     

The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21

BACKGROUND: High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm(-2)) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes. OBJECTIVES: To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. METHODS: Five adult volunteers were exposed to dose series of UVA1 (10-100 J cm(-2)) and, for comparison, narrowband UVB (TL-01) (25-550 mJ cm(-2)) and solar-simulated radiation (SSR) (5.6-30 J cm(-2)) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF. RESULTS: UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean +/- SD cell count per HPF 16 +/- 10), no p53 activation and very little evidence of p21 expression (mean +/- SD cell count per HPF 5.3 +/- 7), in contrast to TL-01 (mean +/- SD cell count per HPF of 11.83 +/- 2.1 SBCs, 146.3 +/- 38 for Do-1, 26.6 +/- 15 for serine 15, 14.9 +/- 12 for serine 392 and 77.9 +/- 30 for p21) or SSR irradiation (mean +/- SD cell count per HPF of 3.5 +/- 1.2 SBCs, 147.5 +/- 62 for Do-1, 54 +/- 50 for serine 15, 38.9 +/- 18 for serine 392 and 56.7 +/- 30 for p21). CONCLUSIONS: These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.     

p53, mdm-2, and p21 waf-1 in the porokeratoses.

The etiology of the porokeratoses is unknown. Overexpression of the p53 tumor suppressor protein and disregulated cell cycle control have been pathogenically implicated. The p53 tumor suppressor gene product is regulated by mdm2 and both gene products influence cell cycle progression through the cyclin-dependent kinase inhibitor p21. Thirty-three cases of the various types of porokeratosis were immunohistochemically studied for p53, mdm2, and p21 proteins. Each of the cases showed increased p53 and decreased mdm2 and p21 expression within keratinocytes underlying cornoid lamella. This study confirms the previous findings of increased p53 staining and expands the potential roles of mdm2 and p21 in the pathogenesis of the porokeratoses.     

p53抗体与肺癌患者化疗敏感性及预后关系的研究

目的 通过对血清p53抗体与化疗敏感性及预后的关系的研究,探讨血清p53 抗体在肺癌中的临床意义.方法 对57例初步诊断为肺癌的患者应用ELISA 法检测血清p53 抗体滴度,经酶联免疫检测仪测吸光值E450,计算抗体指数,进行统计学分析.结果 57例中阳性25 例,阳性率为43.9 %.血清p53 抗体水平与肺癌的病理类型、分期、分化和淋巴结转移有关,与肺癌的预后有关.结论 p53 抗体的产生可能是肺癌发生的早期指征,化疗前测定血清p53抗体可以预测化疗疗效,可以预测肺癌的预后.     

The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation

BACKGROUND: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. OBJECTIVES: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). METHODS: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques. RESULTS: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). CONCLUSIONS: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.     

p53 p21和PCNA在寻常疣中的过度表达

目的：研究寻常疣ｐ５３蛋白、ｐ２１蛋白和增殖细胞核抗原（ＰＣＮＡ）过度表达与人类乳头瘤病毒（ＨＰＶ）感染的关系。方法：采用免疫组化方法对石蜡包埋组织标本进行检测。结果：１５例寻常疣皮损中ｐ５３、ｐ２１以及ＰＣＮＡ阳性标本分别为６例（４０％）、５例（３３％）和９例（６６％）。ｐ５３阳性细胞多位于基底层，ｐ２１阳性细胞则多分布于棘细胞层的中下层，ＰＣＮＡ阳性细胞散在分布于整个增生的表皮。受ＨＰＶ感染的空泡样变性细胞核中均有ｐ５３、ｐ２１以及ＰＣＮＡ过度表达者４例。结论：证实了寻常疣中存在ｐ５３、ｐ２１和ＰＣＮＡ过度表达，并从原位上找到ＨＰＶ感染与ｐ５３、ｐ２１过度表达和细胞异常增生相关联的细胞学证据。     

The relation between p53 mutation and p53 immunostaining in non-melanoma skin cancer

Extensive study of the p53 gene has established its role as a tumour-suppressor gene, and the involvement of mutant p53 in a wide spectrum of human malignancy. Many mutations of p53 result in a protein product that is abnormally stable, so that it becomes readily detectable by immunocytochemistry. In contrast, under normal conditions, it has been considered that levels of wild-type p53 were too low to be detectable. Although positive immunocytochemistry has been used as a marker of mutation, recent evidence suggests that this assumption may not always be valid. We have carried out both PCR-sequencing of exons 5-8 of the p53 gene in 20 basal cell carcinomas (BCC), and immunocytochemistry of these tumours with the anti-p53 antibody Do7. Twenty cases of Bowen's disease, in which we had previously documented mutations, were also immunostained. We report a low rate of p53 mutation in the BCCs we examined (2/20), and a discrepancy between tumours with positive immunostaining and those with mutation in both Bowen's disease and BCC. Of eight tumours in which we detected mutation, only four were immunopositive; of 19 immunopositive samples, only four showed detectable mutation. We discuss the implications of our results for the use of positive immunostaining in clinical diagnosis, and the involvement of p53 in skin carcinogenesis.     

Differential expression of two new members of the p53 family, p63 and p73, in extramammary Paget's disease

Background.  The proteins p53, p63 and p73 are known to be overexpressed and to play important roles in the pathogenesis of many tumours, but the expression of p63 and p73 has not previously been investigated in extramammary Paget's disease (EMPD).
Aim.  To investigate the potential contribution of p53, p63 and p73 in the pathogenesis of EMPD.
Methods.  In total, 35 paraffin wax-embedded tissue samples from patients with EMPD were examined using immunohistochemical staining for p53, p63 and p73.
Results.  All of the 35 EMPD specimens, including all 6 invasive EMPD and 2 metastatic lymph-node specimens, showed nuclear overexpression of both p53 and p73. The expression levels (percentage of positive cells) of p53 and p73 (90.66 ± 12.53% and 80.20 ± 13.07%) in EMPD were significantly higher than those of normal skin. There was a significant correlation between the expression levels of p53 and p73 in EMPD. In 29 of 35 EMPD specimens, there was no nuclear expression of p63, and weak or moderate staining was found in only 6 specimens. The expression level of p63 in EMPD was significantly less than that in normal skin.
Conclusions.  Our study shows that the concordant overexpression of p53 and p73 and the decreased expression of p63 may play a pivotal role in the pathogenesis of EMPD. The decreased expression of p63 may play a more important role in the pathogenesis of EMPD than the overexpression of p53 and p73.     

水泡状胎块中p57、p53及Ki-67的表达及意义

目的：探讨p57、p53和Ki-67的表达在水泡状胎块病理诊断与鉴别诊断中的作用和意义。方法：应用SP法检测74例完全性水泡状胎块（complete hydatidiform mole,CHM）、72例部分性水泡状胎块（partial hydatidiform mole,PHM）和79例水肿性流产胎（hydropic abortion,HA）三组病变组织中p57、p53和Ki-67的表达情况,以正常成熟胎盘（normal mature placenta,NMP）10例为正常对照。同时分析患者的年龄及血中HCG浓度在鉴别各组疾病中的价值。结果：p57在CHM组中的表达明显低于PHM组、HA组及NMP组（P〈0.01）;p53和Ki-67在PHM组和CHM组的阳性表达高于HA及NMP组（P〈0.05）。完全性水泡状胎块的发病高峰在21～25岁,部分性水泡状胎块发病高峰在25～30岁,水肿性流产胎发病高峰在30～35岁。PHM组患者血中β-HCG含量高于CHM组,CHM组又高于HA组。结论：Ki-67和p53的表达对于鉴别水泡状胎块与流产水肿绒毛有重要价值,但对于区别完全性与部分性水泡状胎块其价值有限;而p57蛋白在CHM和PHM的表达和分布有明显差异,可作为水泡状胎块分型诊断的客观辅助指标。HA、PHM和CHM的发病高峰在不同的年龄阶段,可作为辅助鉴别诊断的参考。患者血中HCG的浓度是鉴别水泡状胎块与水肿性流产胎重要的临床客观辅助指标。     

Establishment of ponasterone A-inducible the wild-type p53 protein-expressing clones from HSC-1 cells,cell growth suppression by p53 expression and the suppression mechanism

Gene therapy for a variety of human cancers containing the mutant p53 (mt-p53) gene has been performed by direct injection of a retroviral or adenoviral vector containing the wild-type p53 (wt-p53) gene. Because many individuals with skin squamous cell carcinoma (SCC) have been shown to carry the p53 gene mutation, these patients are candidates for p53 gene therapy. For this reason, we established ponasterone A-inducible the wild-type p53 (wt-p53) protein-expressing clones by transfecting a ponasterone-inducible vector containing the wt-p53 gene into HSC-1 cells, which harbor the mutated p53 ^m/w at codon 173 (GTG → TTG in one allele). Upon the induction of the wt-p53 protein, severe growth suppression was observed. Based on the results of the expression patterns of the p21, p16, RB, BAX and Bcl-2 proteins, as well as on the results of senescence-associated β-galactosidase staining, the suppression was caused by senescence-like growth arrest of the cells. Although it is generally accepted that the suppression of tumor cell growth is caused by p53-induced apoptosis, permanent G1 arrest induced by p53 is also an important part of the growth-suppression mechanism in p53 gene therapy. The present results should expand the possibilities for p53 gene therapy for human skin SCCs containing the mutant p53 gene.     

Analysis of p53 and BAX mutations, loss of heterozygosity, p53 and BCL2 expression and apoptosis in basal cell carcinoma in Korean patients

BACKGROUND: Apart from some Japanese studies, there are few data on the gene mutations involved in the development of basal cell carcinomas (BCC) in Koreans or other Asians. Objective To gain insight into the molecular pathogenesis of BCC in Koreans. METHODS: A collection of 33 cases of BCC were screened for mutations of p53 and BAX genes, p53 and BCL2 expression, loss of heterozygosity (LOH) and apoptosis. RESULTS: Mutations of p53, found in 9% (three of 33) of the cases, were all mis-sense mutations (G-->C transversions) at codon 246 on exon 7. In 6% (two of 33), BAX gene showed frameshift mutations resulting from deletions in the poly(G) tract. LOH on chromosome 9q was seen in 58% (14 of 24), and p53 mutations developed only among the 9q LOH+ cases; LOH on chromosome 18q, where BCL2 gene is located, was found in 13% (four of 30). Immunohistochemical expression of p53 was seen in 27% (nine of 33), and its expression did not coincide with p53 mutations. BCL2 expression was seen in 39% (13 of 33). Apoptosis was revealed in 21%. In BCC, 9q LOH and p53 mutations seem to be closely related; the immunoreactivity of p53 and its mutations were not directly related; and p53 and BCL2 expression were negatively correlated. Frameshift mutations of the BAX gene in BCC are documented for the first time. CONCLUSIONS: Various molecular mechanisms operate with redundant complexity in the pathogenesis of BCC. The LOH on chromosome 9q is the most frequent genetic alteration, as in other races; however, p53 mutations are much less frequent in Koreans than in Caucasians and suggest aetiologies other than ultraviolet radiation.     

Expression of p53 and p16 in actinic keratosis,bowenoid actinic keratosis and Bowen's disease

Introduction Bowen's disease (BD) and bowenoid actinic keratosis (bAK) have traditionally been differentiated according to the presence or absence of dysplasia in the follicular epithelium. p16 has been suggested to be a useful tool to make the differential diagnosis between BD and AK and as a marker of bad prognosis. Materials Five biopsies of BD, five of AK and five of bAK where stained for p53 and p16. Results All lesions showed positive immunostaining of p53, affecting to the lower two thirdss of the epidermis in BD and bAK, and only the basal layer in non‐bAK. All the BD and bAK cases were positive for p16, showing a similar immunostaining pattern, whereas no staining was observed in non‐bAK. Discussion and conclusion These findings suggest a common pathogenic mechanism for BD and bAK. bAK might have worse prognosis than AK. p16 might not be useful as a tool for differential diagnosis between AK and BD because bAK and BD show an extremely similar immunohistochemical pattern.     

Actinic cheilitis: histopathology and p53

BACKGROUND: Chronic actinic cheilitis (AC) is a precursor of squamous cell carcinoma (SCC) of the lip. OBJECTIVES: To evaluate the histopathological characteristics that may help to identify AC more susceptible to carcinomatous transformation, to assess the p53 protein expression in AC, and to determine the value of the p53 expression as a marker of transformation into SCC of the lip. METHODS: Seventy cases of chronic AC were reviewed, 31 of which were associated with SCCs. The samples were obtained from pathology reports of AC and SCC of the lip. Histopathology and immunohistochemical expression of the p53 protein were evaluated in isolated AC and in AC adjacent to SCC. RESULTS: The intensity of the inflammatory infiltrate in the corium was the only histopathological finding significantly associated both with the presence of an invasive tumor and with the degree of epithelial atypia. Most AC (85%) were immunoreactive to the p53 protein. The p53 protein expression in cheilitis was not statistically associated with any other histopathological criteria. CONCLUSIONS: An intense inflammatory infiltrate in AC was predictive of an adjacent invasive SCC. In this study, the p53 protein immunoreactivity was not a marker of malignant transformation.     

Comparison of benign keratoses using p53, bcl-1, and bcl-2

While cell-cycle markers have been used to differentiate benign vs. malignant lesions and to classify malignant lesions, benign keratoses have not been well studied using such markers. We hypothesized that inflammation or irritation of benign keratoses may be related to a shift in the cell cycle. We compared the immunohistochemical staining patterns of 10 seborrheic keratoses (SKs), 10 inflamed seborrheic keratoses (iSKs), and 10 inverted follicular keratoses (IFKs) using antibodies to p53, bcl-1, and bcl-2. Staining with antibodies to p53 was slightly increased in IFKs compared with iSKs or non-inflamed seborrheic keratoses. Bcl-1 staining was similar in all lesions. A population of bcl-2-positive dendritic cells was seen within the epidermal portion of IFKs. Keratinocyte bcl-2 staining was significantly higher in SKs compared with the other two keratoses. Bcl-2 may be increased in SKs as an anti-apoptotic mechanism.