Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma

The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma. Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma. The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively). Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter. Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy.     

CD44v6、P27蛋白在乳腺癌组织中的表达及意义

目的 探讨乳腺癌中CD44v6、p27蛋白表达的意义。方法 应用免疫组化S-P法检测65例乳腺癌中CD44v6、p27蛋白表达。结果 65例乳腺癌中CD44v6、p27蛋白表达总阳性率分别为58.4％、38.4％。CD44v6蛋白阳性表达率与乳腺癌组织学类型、腋淋巴结转移呈正相关(P<0.05,P<0.01),与预后呈负相关(P<0.01),与组织学分级无明显相关性(P>0.05);p27蛋白阳性表达与乳腺癌组织学类型、组织学分级及腋淋巴结转移呈负相关(P<0.05),与预后呈正相关(P<0.05)。结论 CD44v6、p27蛋白表达与乳腺癌浸润、转移及预后显著相关,检测乳腺癌中CD44v6、p27蛋白表达水平,对判断乳腺癌恶性程度、复发转移潜能,评估患者预后及术后选择合理治疗方案有一定参考价值。     

PCNA AND P53 EXPRESSION IN ORAL LEUKOPLAKIA WITH DIFFERENT DEGREES OF KERATINIZATION

Leukoplakias are oral lesions that may have many clinical and histological aspects and they are usually associated with malignancy when dysplastic alterations are shown. However, these transformations may occur in non-dysplastic lesions that show harmless clinical aspect. For this reason, the proposal was to study the p53 and PCNA immunohistochemical expression in non-dysplastic leukoplakias, trying to correlate the results only with the epithelial keratinization degree. For this, 24 leukoplakias degrees I, II and III of Grinspan were used, all of them located in oral mucosa. Most of the leukoplakias showed p53 and PCNA expression in their different keratinization degrees. The p53 marking was confined to the basal and parabasal layers, while the PCNA marking occurred in practically all epithelial layers. The expression pattern of these markers was histologically and statistically similar between the lesions with these keratinization variations. It was evident that non-dysplastic epithelium of leukoplakias showed submicroscopical signs of alterations that lead to malignant transformation, and that the keratinization degree did not correlate to a greater risk of this event.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

p53、nm23蛋白在宫颈鳞癌中的表达及其临床意义

目的研究p53、nm23基因在宫颈鳞癌中的表达及其临床意义.方法采用免疫组织化学S-P法检测45例宫颈鳞癌组织、10例宫颈上皮内瘤变和10例正常宫颈鳞状上皮中p53、nm23蛋白的表达.结果p53、nm23蛋白在宫颈鳞癌中的阳性表达率分别为64.44%、46.67%;在CIN中阳性表达率分别为0、30.00%;在NE组均无表达.p53蛋白在宫颈鳞癌中阳性表达与在CIN、NE中的不表达差异均有显著性(P＜0.01).nm23蛋白在宫颈鳞癌组织中的阳性表达与在NE中的不表达差异有显著性(P＜0.05),但与在CIN中的表达差异无显著性(P＞0.05);与病理学分级、淋巴结转移均呈负相关(P＜0.05,P＜0.01).结论p53、nm23基因参与了宫颈鳞癌的发生发展过程.p53蛋白的过表达是宫颈癌组织恶性变的生物学标志;检测nm23蛋白对判断宫颈癌淋巴结转移和预后有重要意义.     

SB203580对肾缺血/再灌注损伤时细胞凋亡及p38MAPK影响的实验研究

目的　探讨不同时间及不同浓度p38MAPK特异性抑制剂SB2 0 35 80对肾缺血 /再灌注损伤过程中肾功能、细胞凋亡及 p38MAPK活性、表达量、p38MAPK底物的影响。 方法　 4 9只大鼠按缺血 /再灌注及给药时间的不同 ,随机分为 7组 ,每组7只大鼠按正交拉丁方表的顺序 ,经尾静脉注射相同体积、不同剂量的SB ,使其在大鼠体内达到不同的浓度。测定BUN和Scr;用TUNEL试剂盒检测细胞凋亡情况 ;Westernblot技术用于蛋白定性及半定量分析。结果　SB可显著减轻大鼠肾缺血 /再灌注损伤造成的Scr和BUN的升高、肾小管上皮细胞的凋亡及 p38MAPK的激活 ,但存在模型、剂量及给药时机的差异 (P<0 .0 5 ) ,缺血前 3h之前给药 ,使其体内血药浓度达到 5 μmol/L左右可取得较好的效果。 结论　SB可显著减轻大鼠肾缺血 /再灌注损伤 ,在缺血前 3h之前给药 ,同时使其血药浓度达到 5 μmol/L左右可取得最佳效果。     

Effect of N-tosyl-L-phenylalanylchloromethyl Ketone on Tumor Necrosis Factor-alpha -induced NF-κB Activation and Apoptosis in U937 Cell Line

Summary: To investigate the effect of N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) on tumor necrosis factor-alpha-induced NF-κB activation and apoptosis in U937 cell line, changes and subcellular localization of NF-κB/p65 and IκB-α were observed by fluorescencemicroscopy and expression and degradation of IκB-α by flow cytometry. The apoptosis of U937 cells was measured by flow cytometry and electrophoresis of DNA. Immunolfluorescence assay showed that NF-κB/p65,IκB-α only localized in cytoplasm. After TNF-α stimulation, p65 was localized only in nuclei, and IκB-α was only localized in cytoplasm and decreased. The changes of TNF-α stimulation were specifically inhibited by TPCK. Flow cytometry also revealed the downregulation of IκB-α protein during TNF-α-induced apoptosis and the down-regulation was specifically inhibited by TPCK. Flow cytometry also showed the apoptosis of U937 cells after TNF-α induction. DNA ladder can be detected in cells treated by TNF-α. It is concluded that degradation of IκB-α protein and NF-κB/p65 translocation occur during TNF-α-induced apoptosis of U937 cells, suggesting the activation of NF-κB.TPCK-sensitive protease plays an important role in the degradation of IκB-α protein induced by TNF-α in U937 cells. TPCK sensitive protease also plays an important role in the apoptosis of U937 cells induced by TNF-α.     

皮肤鳞状细胞癌中p53、bcl-2和c-myc的表达及意义

目的 研究p53、bcl—2和c—myc在皮肤鳞状细胞癌中的异常表达及其与癌分化程度的关系。方法 应用免疫组织化学S-P法检测58例皮肤鳞状细胞癌中p53、bcl—2和c—myc的表达水平。结果 58例皮肤鳞状细胞癌中p53、bcl-2和c—myc的阳性表达率分别为48．3％、67．2％和32．8％。结论 p53、bcl—2和c—myc异常表达在皮肤鳞状细胞癌的发生、发展中起重要作用，并与皮肤癌的恶性程度有关。     

Effects of decentralization on the levels of GAP-43 and p38 (synaptophysin) in sympathetic adrenergic neurons: a semi-quantitative study using immunofluorescence and confocal laser scanning microscopy

The distribution of GAP-43 in superior cervical ganglion (SCG) and iris were studied in normal animals and following decentralization using immunofluorescence and confocal laser scanning microscopy (CLSM). GAP-43-like immunoreactivity (LI) was compared with p38 (synaptophysin)-LI, and tyrosin hydroxylase (TH)-LI. In the control SCG, GAP-43-LI and p38-LI were mainly localized in nerve terminals around the principal neurons. The neuronal perikarya were negative for GAP-43, but positive for p38 in a perinuclear zone, as well as positive for TH. SIF cells (Small Intensely Fluorescent cells, ganglionic interneurons) were positive for GAP-43, TH and p38. One day after decentralization, GAP-43-LI and p38-LI in nerve terminals around principal neurons had disappeared. Some of the principal neurons showed a weak GAP-43-immunoreactivity. Three days post-decentralization, GAP-43- and p38-positive nerve terminals around the neurons had reappeared in considerable numbers and the intra-ganglionic nerve bundles were positive for both antibodies. In the control irides, GAP-43-LI and p38-LI were distributed in a varicose pattern in the nerve bundles, around blood vessels and in the network of terminals. Double labelling studies showed that GAP-43-LI was colocalized with TH-LI and p38-LI. The network of terminals in the dilator plate of the irides was quantified by measuring the fluorescence intensity of randomly selected areas, using CLSM. Three days after decentralization the intensity of GAP-43-LI and p38-LI had significantly increased. TH-LI had decreased 8 days after decentralization. The results indicate that GAP-43-LI and p38-LI are normally present in the nerve fibers and terminals of both pre- and post-ganglionic neurons in adult rats. The expression of GAP-43-LI and p38-LI in post-ganglionic neurons is preganglionically regulated, as indicated by the increased expression after decentralization. The expression of p38 in these neurons is probably regulated via mechanisms that are separate from those which regulate GAP-43, since it showed a different time course than that of GAP-43-LI.