Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation to p53 mutation and Ki67 antigen expression

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in colorectal cancer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immunohistochemistry and molecular biology in 35 colorectal carcinomas. We compared these findings with each other and with clinical factors. Sixty three percent of tumors expressed p53 whereas seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was heterogeneous: p21-reactive cells were seen in the most differentiated areas. There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumor. On the other hand, there was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.     

急性髓细胞白血病血型变异1例

1　临床资料　患者 ,女 ,6 1岁 ,1999- 0 6 - 0 3日确诊为急性红白血病 (M6 ) .先后 4次住院 ,鉴定血型均为 O型 . 2 0 0 0 - 0 1- 2 2日复诊 ,正反鉴定表明 ,患者红细胞与抗 - B不凝集 ,与抗 - A凝集 ,血清中有抗 - B抗体 (表 1) ,吸收释放试验证实为 A型 (表2 ) .输 A型浓缩红细胞 2 μ,无不良反应 .表 1　血型正反鉴定试剂血清试剂红细胞标本抗 A 抗 B 抗 A+ B Ac Bc Oc被检红细胞 2 + -3+ ---自身血清 -3+ -表 2　吸收、放散试验被检 RBC吸收抗血清后上清被检 RBC吸收抗血清后释放液试剂细胞抗 A修正液抗 B修正液抗 A修正液抗…     

综合疗法治愈狼疮性急性肾衰1例

1　病例报告　患者 ,女 ,6 0岁 ,因反复发热 2 5 a、全身性关节疼痛 2 3 a,双下肢水肿 2 mo,腹胀、尿少 1mo,于 1998- 10 - 2 0入院 .1975年患者出现发热 ,全身关节疼痛 ,四肢关节周围皮肤出现结节性红斑 ,触之疼痛 ,多次化验血沉 115 mm· h- 1 ,抗核抗体阴性 ,类风湿因子阳性 ,未找到狼疮细胞 ,诊断为“类风湿性关节炎”.1986年因上述症状复发再次入我院 ,多次检查后发现血抗核抗体 ( ) ,抗双链 DNA抗体 ( ) ,临床确诊为系统性红斑狼疮 (SL E) ,狼疮性肝炎 ,狼疮性胸膜炎 ,狼疮性肺炎 .经治疗好转 ,但上述症状反复发作 .此次上述症状复…     

A risk-benefit assessment of amifostine in cytoprotection.

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy and using intensified chemotherapy with or without autologous bone marrow rescue. Dose intensity usually increases objective response rates of antineoplastic drugs and might, in some circumstances, improves survival. However, unacceptable acute and/or cumulative toxicity often impairs the proper management of patients, leading to dose reduction or treatment delay, thus reducing the efficacy and potentially the quality of life of patients. Therefore, considerable efforts have been made to manage, to prevent, and to delay many acute and cumulative treatment-related toxicities. Amifostine (WR-2721 ) is a multiorgan cytoprotector which has demonstrated cytoprotective effects, in vitro and in vivo, against the most common cytotoxic drug-related toxicities and against radiation-induced adverse effects in healthy tissues. In vitro and in vivo, cytoprotection was observed in several organs including kidney, haematopoietic stem cells, myocardial cells, neural cells, and mucosa, without detectable protection of malignant cells. In addition, in preclinical studies, amifostine appeared to be able to reduce the risk of radiation-induced secondary neoplasms. Phase I studies showed that nausea/vomiting and hypotension are the dose-limiting toxicities of amifostine and these may be controlled by reducing the duration of injection of amifostine. Phase II and randomised studies have confirmed the efficacy of amifostine in protecting against radiotherapy-induced mucositis, cisplatin-induced nephrotoxicity, cyclophosphamide-induced neutropenia and carboplatin-induced thrombocytopenia. Importantly, the cytoprotection of healthy tissues occurred without any significant deleterious effect on response rate, time to progression, and survival of patients receiving amifostine. However, in addition to the potential quality of life benefit, the most important question of whether the use of a cytoprotective agent might translate into the possibility of maintaining the dose intensity of anticancer therapies has still to be answered. The real benefit of amifostine in the overall management of patients with cancer requires additional studies to determine whether this chemoprotective approach can be of benefit to patients by increasing response rate, time to progression, and long term survival in patients receiving the more recent combination therapies involving new drugs such as the taxanes and oxaliplatin.     

Assessment of immunological status in the critically ill

The systemic inflammatory response (SIRS) results from various types of injuries such as severe infection, trauma, ischemia-reperfusion and major surgery including cardiac surgery with cardio-pulmonary bypass. This response involves immune cell activation and a complex network of proinflammatory cytokines, which may induce multiple organ failure when uncontrolled. The monocyte plays a central role in the response to infection with the release of TNF, IL-1, and IL-12. In addition, monocytes present antigens to T lymphocytes. An optimal antigen presentation requires the expression of MHC class II HLA-DR on monocytes surface and of co-stimulatory molecules such as CD54 on monocytes and LFA-1 on lymphocytes. It has become increasingly apparent that the pro-inflammatory response is balanced by concomitant anti-inflammatory mechanisms that results in monocyte deactivation, characterized by a decrease in HLA-DR expression and the release of anti-inflammatory cytokines such as IL-10. This counterregulatory response, if prolonged or predominant, may predispose the patient to a higher risk of infection. Further studies need to be conducted to precise: 1) the intensity of depression of the surface molecule expression assessing monocyte function, such as HLA DR and CD54; 2) the level of IL-10 and IL-12 release in patients with severe sepsis; 3) the immunomodulating effects of frequently used treatments in these patients with severe sepsis and in surgical patients; 4) the time course of recovery; 5) if the monitoring of HLA-DR, CD54, IL-10 and IL-12 will better predict the clinical outcome than clinical parameters.