Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies from the same tumour.

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of L-[1-13C]leucine as a 'flooding dose'. 2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2-33.9%/day, with a mean rate (+/- SEM) of 22.5 +/- 2.6%/day. 3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3-15.9%/day, with a mean rate (+/- SEM) of 10.3 +/- 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours (P less than 0.001). 4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (+/- SEM) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 +/- 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.     

Tumour cell growth in culture: dependence on arginine

The amino acid arginine has been shown to affect the growth of several tumours, although the mechanisms of its action are not clear. In the present study, using a human breast tumour cell line (MCF-7), we investigated the arginine requirements of tumour cells for optimal protein synthesis and growth, and the metabolic pathway responsible for the arginine-dependent growth. The results showed that MCF-7 cells are highly dependent on arginine for growth and that the requirement for arginine is much higher than for an indispensable amino acid, leucine, indicating that arginine is needed for pathways other than protein synthesis. In arginine-free cultures, growth could be completely restored by the urea cycle intermediate citrulline. However, arginine could not be replaced by the urea cycle intermediate and the direct precursor for polyamine synthesis, ornithine, or by the polyamine putrescine, suggesting that the high dependence on arginine is not due to a requirement for polyamine synthesis. Moreover, inhibition of NOS [NO (nitric oxide) synthase] did not affect cell protein synthesis and growth, and the arginine analogue and substrate for NOS, homoarginine, could not replace arginine, implying that the conversion of arginine into NO is not involved in the growth-promoting effects of arginine. The major determinant for the high dependence of MCF-7 cells for arginine was found to be the irreversible conversion of this amino acid into ornithine by the intracellular enzyme arginase. The conversion into ornithine caused a progressive depletion of arginine from the culture medium, which ultimately inhibited cell protein synthesis and halted growth. Intracellular arginase activity may be the major factor determining the requirement for arginine of all cells in culture.     

Ki67在乳腺癌组织中的表达及其临床意义研究

目的探讨乳腺癌组织Ki67表达水平及其与疾病分型、患者预后等的相关性。方法收集2013年1月至2015年12月于本院治疗的93例乳腺癌患者及20例乳腺良性疾病患者临床资料,分析Ki67指数与疾病病理参数及实验室指标的相关性。结果 93例乳腺癌患者Ki67指数水平为1%~90%,中位数为21.65%。乳腺癌组织学分级、肿瘤直径、人表皮生长因子受体2(HER2)表达状态与Ki67指数相关(P0.05),年龄、绝经状态、肿瘤TNM分期、腋窝淋巴结转移状态、雌激素受体(ER)及孕激素受体(PR)表达状态与Ki67指数无关(P0.05)。三阴性乳腺癌、非三阴性乳腺癌及乳腺良性疾病患者Ki67指数中位数依次为30.15%、20.26%、4.67%,三者间Ki67指数比较差异有统计学意义(P0.05)。Ki67指数水平与乳腺癌分型相关(P0.05),与患者血细胞比容和血钾浓度水平相关(P0.05)。结论 Ki67指数联合其他指标可用于乳腺癌诊治及患者预后判断,具有一定的临床应用价值。     

表皮生长因子受体-2和P53及Ki67的表达状况对预测乳腺癌化疗敏感性的临床价值

目的 探讨表皮生长因子受体-2（CerbB-2）、P53和Ki67的表达状况对预测乳腺癌化疗敏感性的临床价值.方法 检测86例乳腺癌患者瘤体组织CerbB-2、P53和Ki67的表达水平,观察每例患者新辅助化疗的疗效,比较CerbB-2、P53和Ki67不同表达水平的患者接受新辅助化疗的疗效差异.结果 CerbB-2阴性的乳腺癌患者对新辅助化疗的有效率为89.1%,明显好于CerbB-2阳性患者的5 1.6%：Ki67阳性的乳腺癌患者对新辅助化疗的有效率为82.8%,疗效好于Ki67阴性患者的60.7%：CerbB-2阴性并Ki67阳性患者对新辅助化疗的有效率为94.7%.P53表达状况对新辅助化疗的敏感性没有影响.结论 乳腺癌患者瘤体组织CerbB-2阴性和Ki67阳性患者对新辅助化疗敏感性好,CerbB-2阴性并Ki67阳性可作为筛选乳腺癌临床化疗患者的生物学指标.     

乳腺癌Raf-1和Ki67表达及新辅助化疗前后变化研究

目的 探讨Raf-1和Ki67在乳腺癌表达水平与临床病理特征相关性,并研究其在新辅助化疗前后的变化.方法 采用免疫组织化学方法（SP法）检测186例乳腺癌病理组织中的Raf-1和Ki67的阳性表达情况,其中包括68例新辅助化疗前后的组织标本.结果 乳腺癌组织中Raf-1和Ki67的表达与淋巴结有无转移和病理分期、临床分期等有关（P＜0.001）;新辅助化疗后Raf-1和Ki67的阳性表达较新辅助化疗前均有所下降,差异有统计学意义（P ＜0.001）;Raf-1和Ki67在新辅助化疗前后的表达变化值与化疗疗效明显相关（P＜0.001）,新辅助化疗效果越好,Raf-1蛋白和Ki67下降越明显.结论 Raf-1和Ki67阳性表达与乳腺癌的发生发展具有密切的相关性.新辅助化疗影响Raf-1和Ki67的表达,新辅助化疗后应重新检测Raf-1和Ki67的表达,为后续治疗及判断预后提供指导.     

Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.

L-arginine is required for the fungistatic action of murine macrophages in vitro. To further investigate this requirement, L-arginine metabolism by macrophages was measured under conditions where fungistasis either succeeded or failed. Macrophage fungistasis correlated with metabolism of L-arginine to citrulline, nitrite, and nitrate. The metabolic rate was dependent on extracellular L-arginine concentration, reaching a maximum of 67 nmol nitrite/h per mg protein. It accounted for one-third of arginine consumed by fungistatic macrophages. Equimolar amounts of citrulline and total nitrite plus nitrate accumulated in medium. This was consistent with the hypothesis that one of the equivalent guanidino nitrogens of L-arginine was oxidized to both nitrite and nitrate leaving L-citrulline as the amino acid reaction product. The analogue, NG-mono-methyl-L-arginine, selectively inhibited nitrogen oxidation and it was shown previously that it inhibited fungistatic capability. Resident macrophages were not fungistatic and their nitrogen oxidation was low. Once macrophages began producing nitrite/nitrate, protein synthesis was not required during the next 8 h for either fungistasis or nitrogen oxidation. Two-thirds of L-arginine consumption was due to macrophage arginase yielding L-ornithine and urea, which accumulated in medium. This activity was dissociated from macrophage fungistasis. Nitrogen oxidation metabolism by macrophages is linked to a mechanism that inhibits proliferation of fungi. This may involve synthesis of an intermediate compound(s) that has antimicrobial properties.     

In situ distribution of oncogene products and growth factor receptors in breast carcinoma: c-erbB-2 oncoprotein, EGFr, and PDGFr-beta-subunit

An increasing body of evidence suggests that breast tumour growth is mediated by oncogene products and growth factors which are or which act through cell surface receptors. The aims of the present study were to determine how three of these receptors, c-erbB-2 protein, epidermal growth factor receptor (EGFr) and the beta-subunit of platelet-derived growth factor receptor (PDGFr-beta-subunit), can effectively be demonstrated by immunohistochemical methods in breast tumors, how these receptors are distributed at the cellular level and how their expression correlates with well-established prognostic indicators including hormone receptors and proliferative index. We examined frozen tissue sections of 50 invasive human breast carcinomas, including 45 ductal, four lobular, and one mucinous tumours, by immunocytochemical methods to determine the in situ distributions of c-erbB-2, EGFr, and PDGFr-beta-subunit. We compared staining for c-erbB-2 protein in frozen sections with that in paraffin sections of the same 50 tumours. The immunohistochemical labelling results were compared with tissue hormone receptor content and growth fraction determined by Ki-67 labelling. Strong labelling of tumour cells in frozen sections was detected in 22% of cases, all of the ductal type, stained with rabbit antiserum to c-erbB-2. Labelling for c-erbB-2 protein was generally weaker in paraffin sections than in frozen sections and in six of 11 positive cases, specific staining could be detected only in frozen sections. In immunostains with monoclonal antibody to EGFr, rare cells within tumour were labelled in 60% of the carcinomas. Using a monoclonal antibody to the beta-subunit of PDGFr, consistent labelling of fibrillary cellular processes in the walls of blood vessels and in fibrous stroma around tumour cell nests was detected, but there was no labelling of tumour cells themselves. C-erbB-2 oncoprotein positive tumours were found to be more often oestrogen receptor negative (P less than 0.005) or oestrogen and progesterone receptor negative (P less than 0.01) than c-erbB-2 negative tumours. No significant correlation was observed between c-erbB-2 expression and Ki-67 growth fraction.     

Ki67表达在乳腺癌新辅助化疗中的临床意义

目的探讨Ki67表达与乳腺癌新辅助化疗（neoadjuvant chemotherapy,NACT）疗效的关系。方法我院2009年6月至2011年3月收治的接受NACT、化疗后可手术的52例乳腺癌患者,采用免疫组化方法检测NACT前后乳腺癌组织中Ki67的表达情况,采用Miler and Payne（MP）治疗反应评价方法评价术后乳腺癌组织的病理治疗反应水平,统计学分析二者间关系。结果Ki67高表达组NACT后病理有效率（67．74％）高于低表达组（23．81％）,Ki67表达明显下降组（65．52％）病理有效率高于轻度下降组（26．09％）,差异均有统计学意义（P〈0．01）。结论Ki67表达水平可以作为乳腺癌NACT的敏感性预测指标,NACT前后Ki67表达下降水平可作为评价化疗效果的重要指标。     

Cyclin-dependent kinase 15 upregulation is correlated with poor prognosis for patients with breast cancer

ObjectiveTo investigate the clinical significance of cyclin-dependent kinase (CDK) 15 in breast cancer.MethodsThis prospective observational study enrolled 154 patients with breast cancer. Tumor tissues and paired paracancerous normal tissues were collected. Additionally, 85 samples of benign breast lesions were obtained from patients with mammary gland hyperplasia. Patient characteristics were recorded, and CDK15, human epidermal growth factor receptor (HER)2, estrogen receptor, progesterone receptor, and Ki67 immunohistochemical expression were determined.ResultsThe rate of strong CDK15 expression was 63.6% (98/154) in breast cancer tissues, which was remarkably higher than that in benign breast lesions (34.1%, 29/85). Similarly, the ratio of strong CDK15 expression was markedly higher in tumor tissues (63.6%, 98/15) than in paracancerous normal tissues (27.3%, 42/154). Pearson’s analysis showed that the CDK15 expression score was positively correlated with HER2 and Ki67. Patients with high CDK15 expression showed markedly higher ratios of TNM stage III to IV, lymph node metastasis, and increased tumor diameters but a significantly lower rate of ductal carcinoma in situ. The median survival time of these patients was significantly shorter. Kaplan–Meier curve analysis showed that low CDK15 expression predicted longer survival times.ConclusionUpregulated CDK15 predicted poor clinical outcomes in breast cancer.     

Expression of 34βE12 may be an independent predictor of survival in breast cancer

ObjectivesTo investigate the relationship between high-molecular-weight cytokeratin (34βE12) and clinicopathological parameters (including HER-2, Ki67 and steroid receptors) in breast cancer to determine its usefulness as a prognostic marker.MethodsIn this retrospective study, the expression level 34βE12 was assessed in surgically resected breast cancer specimens by immunohistochemical staining. Data were correlated with the patients’ clinicopathological parameters.ResultsOf the 348 breast cancer tissue samples, 232 (67%) showed positive expression of 34βE12. There were statistically significant differences between the positive and negative 34βE12 expression groups in tumour size, lymph node involvement, oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. There were no differences between groups in age, tumour grade, or Ki67 status. In addition, patients who were positive for 34βE12 had significantly extended overall survival. In multivariate analysis, the expression level of 34βE12 was found to be a significant independent prognostic factor.ConclusionThese results suggest that positive 34βE12 expression is associated with a favourable outcome in breast cancer and so may be a useful prognostic factor. Further studies are required to confirm these results.     

Expression patterns of cyclins D1, E and cyclin‐dependent kinase inhibitors p21waf1/cip1, p27kip1 in colorectal carcinoma: correlation with other cell cycle regulators (pRb,p53 and Ki‐67 and PCNA) and clinicopathological features

Aberrations in the cell cycle regulators are common features of many tumours and several have been shown to have prognostic significant in colorectal cancer. The expression patterns of cyclins D1 and E as well as cyclin‐dependent kinase (CDK) inhibitors p21waf1/cip1 and p27kip1 and their interrelationship with other cell cycle checkpoint proteins [p53, pRb, Ki‐67 and proliferative cell nuclear antigen (PCNA)] were investigated in colorectal cancer in order to ascertain coregulation and influence on tumour behaviour or survival. These molecular markers were localisated immunohistochemically using the monoclonal antibodies anticyclin D1 (DCS‐6), anticyclin E (13A3), anti‐p21 (4D10), anti‐p27 (1B4), anti‐p53 (DO7), anti‐Rb (AB‐5), MIB1 and PC10 in colorectal cancer tissue from 97 patients. Data were analysed statistically using the spss software program. Overexpression of cyclin D1, cyclin E and p21waf1/cip1 proteins (>5% positive neoplastic cells) was observed in 5.9%, 30% and 7.2% of the cases respectively. Increased levels of cyclin D1 (p = 0.0001) and p21waf1/cip1 protein (p = 0.03) in tumours with mucous differentiation were observed. Overexpression of cyclin D1 was correlated with tumour stage (p = 0.03), the lymph node involvement (p = 0.02), as well as p21waf1/cip1 protein expression (p < 0.0001). Cyclin E was positively correlated with p21waf1/cip1 (p = 0.014), as well as with the cell proliferation as measured by PCNA‐labelling index (p = 0.011) and Ki‐67 score (p = 0.007). A positive relationship of p21waf1/cip1 expression with the proliferative‐associated index Ki‐67 was noted (p = 0.005). Downregulation of p27kip1 was observed in 47.4% of the cases and was correlated with downregulation of pRb (p = 0.002) and PCNA score (p = 0.004). The prognostic significance of cyclins D1, E and CDK inhibitors p21waf1/cip1, p27kip1 in determining the risk of recurrence and overall survival with both univariate (long‐rang test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. In conclusion, these findings suggest that, the levels of the cell cycle regulators studied, do not seems to have a prognostic value, in terms of predicting the risk of early recurrence and overall survival. In addition, the interrelationships, probably means their contribution to the regulation of cell growth, through different pathways in colorectal carcinogenesis.     

乳腺癌Ki一67P—gp表达创面脱落细胞检查临床意义相关性研究

目的研究不同病期乳腺癌中Ki一67、P—gp表达及根治术中创面冲洗液脱落细胞情况,揭示其三者之间的相关性及与预后的关系。方法采用免疫组化方法检测90例不同病期乳腺癌患者手术根治标本中Ki一67、P—gP表达水平,采用离心沉淀法检测其根治手术创面冲洗液中有无癌细胞,同时对上述病例跟踪随访3年,观察其有无复发转移情况及3年生存率,计算Pearson相关系数。结果Ki一67在乳腺癌Ⅰ、Ⅱ、Ⅲ期的阳性表达率分别是60．0％,71．8％,90．5％;P—gp阳性表达率分别为36．7％,38．5％,57．1％;脱落细胞的阳性率分别是3．3％,7．7％,14．3％。结论Ki一67、P—gp、创面脱落细胞在乳腺癌Ⅰ、Ⅱ、Ⅲ期阳性表达率存在正相关关系。     

Effect of N-substituted arginine compounds on blood pressure in anesthetized rats.

Inhibition of endothelium-dependent relaxation by NG-monomethyl L-arginine (L-NMMA) and its reversal by excess L- but not D-arginine is used to support the hypothesis that the endothelium-derived relaxing factor (EDRF) is generated exclusively from the metabolism of L-arginine. However, in freshly isolated vascular tissues, L-arginine is a poor vasodilator when compared to the N-substituted arginine compound, N alpha-benzoyl L-arginine ethyl ester (BAEE). Here, we show that such N-substituted compounds are potent hypotensive agents in anesthetized rats. In contrast, L-arginine elicits hypotensive effect only at higher concentrations (greater than 100 mg/kg). This effect of L-arginine is not antagonized by L-NMMA. Furthermore, D-arginine, L-homoarginine and L-lysine also have hypotensive effects at these concentrations. Indomethacin treatment partially attenuates the hypotensive effects of the basic amino acids. In contrast, the hypotensive effect of BAEE is antagonized by L-NMMA in a dose-dependent manner and by methylene blue, which is an inhibitor of soluble guanylate cyclase. In addition, substitution at the arginine moiety determines the hypotensive effect. When the amino acid glycine is inserted between the benzoyl group and arginine as in benzoyl-glycine-arginine, significant attenuation of the hypotensive effect is observed. These data demonstrate that compounds such as BAEE generate an EDRF-like agent in vivo and basic amino acids such as L-arginine elicit hypotension at concentrations above 100 mg/kg by mechanisms other than the generation of EDRF.     

乳腺癌彩色多普勒超声的诊断及鉴别诊断

目的探讨彩色多普勒超声在乳腺癌诊断与鉴别诊断中的应用价值。方法回顾性分析经手术病理证实的68例乳腺癌患者与67例乳腺良性肿块患者声像图资料,对乳腺癌二维超声图像与彩色多普勒血流图像(CDFI)特点进行总结,并将超声与病理结果相对照。结果乳腺恶性肿块与乳腺良性肿块的二维声像图存在差别;彩色多普勒血流图检查恶性肿块血流显示率为96%,良性肿块血流显示率为48%;恶性肿块多表现为穿入性动脉血管(76%),并呈高阻血流信号(RI>0.7)。结论彩色多普勒血流的分布特点与频谱变化是反映乳腺新生血管的一个重要特征,二维超声与彩色多普勒血流图结合能进一步提高乳腺癌的诊断率。     

Effects of high doses of glucocorticoids on free amino acids,ribosomes and protein turnover in human muscle

BACKGROUND: Treatment with glucocorticosteroids causes a negative nitrogen balance, but the kinetic mechanisms responsible for this catabolic effect are controversial. We investigated the effects of 60 mg day(-1) prednisolone on protein synthesis and degradation in human skeletal muscle. MATERIALS AND METHODS: Healthy adults (n = 9) were studied in the postabsorptive state, before and after 3 days of prednisolone treatment. The L-[ring 2,6(-3)H(5)]-phenylalanine tracer technique, concentration and size distribution of the ribosomes, mRNA content of the ubiquitin-proteasome pathway components in muscle, phenylalanine flux across the leg, and the free amino acid concentrations in skeletal muscle were used to study muscle protein metabolism. RESULTS: The concentrations of most amino acids in arterial blood increased after prednisolone. There were also increased effluxes of phenylalanine, asparagine, arginine, alanine, methionine and isoleucine from the leg. The rate of protein degradation, as measured by the appearance rate (Ra) of phenylalanine, increased by 67% (P = 0.023) which, together with a doubling of the net release of phenylalanine from the leg (P = 0.007), indicated accelerated protein degradation. The pathway was not identified but there was no significant increase in mRNAs' encoding components of the ubiquitin-proteasome pathway. There was a 6% reduction in polyribosomes (P = 0.007), suggesting a decrease in the capacity for protein synthesis, although there was no measured decrease in the rate of protein synthesis. CONCLUSIONS: These findings indicate that high doses of prednisolone lead to a sharp increase in net protein catabolism, which depends more on enhanced protein breakdown, and an uncertain effect on protein synthesis. The mechanisms stimulating proteolysis and the pathway stimulated to increase muscle protein degradation should be explored.     

ER、PR以及Ki-67状态与乳腺癌新辅助化疗疗效的相关性

目的 探究雌激素受体(ER)、孕激素受体(PR)以及Ki67抗原(Ki67)状态与乳腺癌(BC)新辅助化疗疗效的相关性.方法 选取本院2015年12月至2020年5月216例乳腺癌患者,术前均进行新辅助化疗.采用免疫组织化学染色检测ER、PR、Ki-67,评价疗效,分析ER、PR、Ki-67与疗效的关系.结果 总有效率...     

Metabolism in hypothermically perfused human kidney carcinoma: utilization and production of amino acids and glucose

The metabolism of human kidney carcinoma was studied during hypothermic perfusion. Ten kidneys with carcinomas of different size were perfused in a Gambro perfusion machine for 6 days at +8 degrees C to +10 degrees C. The tumourous kidneys were allocated to one of two groups depending on the relative size of the tumour. Tumours occupying more than 40% of the total kidney volume were designated as "large tumours" and tumours occupying less than 40% as "small tumours". The net glucose uptake was greater during perfusion of kidneys with large tumours than during perfusion of kidneys with small tumours. A lower gluconeogenesis was found in kidneys with large tumours compared to perfusion of kidneys with small tumours and this could explain a large part of the difference in net glucse uptake. The uptake of fatty acids per unit kidney weight was lower during perfusion of kidneys with large tumours. A considerable uptake and release of amino acids were found in both groups. The uptake of proline, aspartate, glycine, and arginine as well as the release of alanine and serine was lower during perfusion of kidneys with large tumours. The nitrogen balance was negative in both groups, with a net release of amino acids to the perfusate. The results suggest a higher glucose uptake, a lower gluconeogenesis, a lower fatty acid uptake and a decreased metabolization of amino acids in the tumour compared to the renal tissue. The model appears promising for studies of human kidney carcinomas at various experimental conditions.     

Increased expression of osteopontin in patients with triple-negative breast cancer

Background Patients with triple‐negative [oestrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER‐2/neu) negative] breast cancer, accounting for about 15% of breast cancer cases, are associated with aggressive histology, poor prognosis and shorter survival. Osteopontin is a chemokine‐like phosphorylated glycoprotein that plays important role in cancer progression and is found to be a metastasis‐associated protein in breast cancer. The goal of the study was to evaluate osteopontin protein expression levels in triple‐negative breast carcinomas to determine if they correlated with clinicopathological parameters, thus providing additional support for osteopontin functioning and better understanding of triple‐negative breast cancer. Materials and methods A database of 239 patients, in whom all three markers (ER, PR, and HER‐2/neu) were available, was reviewed. We performed osteopontin protein expression analyses by means of immunohistochemistry on 117 breast carcinoma tissue samples, and then assessed the mean value of osteopontin expression against triple‐negative status and clinicopathological parameters. Results Of the 239 patients in the study, 47 were classified as triple negative. Of the 117 osteopontin‐test patients in this cohort, mean osteopontin levels were significantly higher in the triple‐negative breast cancers than in non‐triple‐negative subtype (P = 0·035). TNM (tumours, nodes, metastases) stage were significantly associated with osteopontin levels (P = 0·038). Univariate analysis showed tumour cell osteopontin positivity above an optimized cut‐point to be significantly associated with decreased disease‐free survival, but not overall survival. In the multivariate model, osteopontin was an independent prognostic factor for disease‐free survival. Conclusions Patients with osteopontin overexpression develop predominantly triple‐negative tumours. Osteopontin overexpression is associated with tumour aggressiveness and poor prognosis.     

乳腺癌患者组织中FOXA1、BRCA-1表达与临床病理参数的相关性

目的 研究乳腺癌患者组织中叉头框蛋白A1(FOXA1)、乳腺癌易感基因1(BRCA-1)表达与临床病理参数的相关性.方法 回顾性分析2018年3月至2019年5月于本院收治的97例乳腺癌患者的临床病理资料,采用免疫组织化学法检测FOXA1、BRCA-1的表达,采用Pearson法分析FOXA1、BRCA-1的表达与乳腺...     

Evaluation of somatostatin receptors in human cancer.

The binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.