Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.     

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

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P38蛋白在大肠癌中的表达及其临床意义

目的:探讨人大肠癌中有丝分裂原激活蛋白激酶P38的表达及其临床意义.方法:应用免疫组织化学SABC法检测46例大肠癌组织及其癌旁正常粘膜中P38蛋白表达情况.结果:P38蛋白的表达定位于胞质中,胞核中无表达.P38在大肠癌中的阳性表达率为95.65%,在癌旁组织中阳性表达率为33.13%.P38在大肠癌中的表达明显高于癌旁组织,有显著的统计学差异(P＜0.01).P38的表达与年龄、性别、肿瘤大小、肿瘤位置无明显相关(P＞0.05).P38的表达与Dukes分级,组织分化程度及有无淋巴结转移有显著差异(P＜0.01).结论:大肠癌组织中P38蛋白处于过度表达状态,与大肠癌的发生,发展和转移密切相关.     

妊娠期接受MRI磁场照射对子代大鼠不同发育期MAPK的影响

【目的】　研究妊娠期接受磁共振 (magneticresonanceimaging ,MRI)复合磁场照射对子代大鼠不同发育期脑部丝裂原活化蛋白激酶 (mitogenactivatedproteinkinase ,MAPK) /细胞外信号调节蛋白激酶 (extracellularsignalregulatedproteinkinase ,ERK )表达的影响。 　【方法】　SD孕鼠妊娠第 12～ 18d给予 0 .3 5TMRI磁场照射 ,雌性子鼠1、2、5月龄时进行大脑切片免疫组化SP方法染色 ,并用图像分析仪进行半定量分析。　【结果】　MAPK/ERK免疫反应在大鼠脑切片上广泛表达 ;随着年龄增长 ,未发现其表达的变化 ;在各年龄段子鼠照射组和对照组间MAPK/ERK的免疫反应表达差异均无显著性 (P >0 .0 5 )。　【结论】　妊娠期MRI磁场照射后并未引起子代大鼠MAPK/ERK免疫反应表达的异常     

联合转染p53与血管生成抑素基因对人胃癌细胞系SG7901生长的影响

目的探讨联合转染p53和血管生成抑素(AS)基因对人胃癌细胞系SG7901生长的影响。方法用脂质体转染法分别将p53、AS基因、p53和AS基因转染人胃癌细胞系SG7901。以RT-PCR法检测转染后细胞目的基因的表达,通过细胞集落形成实验、MTT生长曲线、细胞周期检测观察其生物学特性变化。结果p53或AS基因均能抑制转染细胞的生长,而联合转染两种基因的细胞生长抑制更明显。结论p53和AS基因具有协同抑制恶性肿瘤细胞生长作用,提示联合多种基因可能有利于恶性肿瘤的基因治疗。     

Immunohistochemical characterization of endocervical papillary serous carcinoma

Abstract.   Nofech-Mozes S, Rasty G, Ismiil N, Covens A, Khalifa MA. Immunohistochemical characterization of endocervical papillary serous carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 286–292.
Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 ± 19.1), while the conventional cell subtypes control group were 28–90 years old (mean = 47.5 ± 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology ( P = 0.001 and P = 0.016, respectively) as shown by Cochran–Mantel–Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.     

p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

INTRODUCTION Sharing characteristics of stress mediators[1], cen-tral interleukin-1β (IL-1β) is very important in cardio-vascular and behavioral responses to stressors[2-4]. Itcan induce similar hypertensive responses to stress viacardiovascular regulatory regions[5]. We observed pre-viously that central IL-1β mediated cardiovascular re-sponses to some stressful stimuli, such as conditionedfear stimuli and footshock[6]. Many stressful stimulimay increase IL-1β mRNA expression and …     

汉黄芩苷对缺氧复氧诱导H9c2心肌细胞损伤及P38和ERK1/2表达的影响

目的 探讨汉黄芩苷（Wog）对缺氧复氧诱导H9c2心肌细胞损伤及P38和ERK1/2表达的影响。方法 培养心肌细胞H9c2构建缺氧复氧模型（A/R）,给予Wog低、中、高剂量（12.5、25、50 μM）处理24h,采用CCK8检测48 h后细胞活力,Hochest染色检测细胞凋亡,ELISA检测细胞上清液中心肌损伤标记物［肌酸激酶（CK）,肌酸激酶同工酶（CK MB）、肌红蛋白（Mb）］和炎性细胞因子［白介素6（IL-6）、白介素1β（IL-1β）和诱导型一氧化氮合酶（iNOS）］的含量,生化试剂盒检测氧化应激指标［超氧化物歧化酶（SOD）、丙二醛（MDA）及乳酸脱氢酶（LDH）］的含量,Western blot检测相关蛋白［B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关x蛋白（Bax）、半胱氨酸天冬氨酸蛋白酶3（Caspase-3）、Caspase-9］、丝裂原活化蛋白激酶P38及细胞外调节激酶（ERK1/2）的表达。 结果 低、中、高剂量Wog处理缺氧复氧模型细胞H9c2,细胞存活率、Bcl-2及SOD的表达显著升高,凋亡率、Bax、Caspase-3、Caspase-9、CK、CK-MB、Mb、IL-6、IL-1β、iNOS、MDA、LDH、P38及ERK1/2的表达显著降低（均P＜0.05）。 结论 汉黄芩苷可通过改善炎症反应和氧化应激损伤,减少心肌细胞的凋亡,对缺氧复氧诱导H9c2心肌细胞损伤具有一定的保护作用,可能与下调P38、ERK1/2磷酸化有关。