多药耐药相关蛋白在人恶性黑色素瘤转移性淋巴结组织中的表达意义 …

目的 研究多药耐药相关蛋白（ＭＲＰ）在人恶性黑色博物馆生淋巴结组织中的表达及其与以顺铂、氮唏咪胺为主的联合化疗中（ＰＤＢＶ）疗效的关系。方法 免疫组织化学技术对石蜡包埋组织标本进行检测。结果 ２６例晚期恶性黑色素素瘤患者转移性淋巴结中ＭＲＰ表达阳性检出率为３８．５％（１０／２６）。ＭＲＰ表达与ＰＤＢＶ化疗疗效无显著相关（Ｐ〉０．０５）。结论 ＭＲＰ在人恶性黑色素瘤转移性淋巴结组织中有一定程度表达，     

99Tcm-甲氧基异丁基异腈SPECT预测肺癌多药耐药及化疗疗效

化疗作为肺癌特别是非小细胞肺癌综合治疗的主要手段之一.肺癌耐药尤其是多药耐药成为化疗失败的重要原因.早期发现多药耐药,选择合适的化疗方案,对于肺癌患者至关重要.肺癌的多药耐药与多药耐药相关蛋白(MRP)在肺癌中表达相关,某些亲脂性抗癌化疗药物和99Tcm-甲氧基异丁基异腈(99Fcm-MIBI)可能同为某些MRP的底物,它们在肿瘤细胞中的滞留与MRP的表达相关.因而行无创性的肺99Tcm-MIBI SPECT,在化疗前预测体内MRP的表达或在化疗过程中监测MRP表达的变化,有助于预测肺癌多药耐药及化疗疗效.     

X线照射对人鼻咽癌细胞株MRP基因和MRP表达的影响

化疗药物可以诱导肿瘤细胞多药耐药相关基因(MRP基因)及其蛋白(MRP)的过度表达,从而产生多药耐药,导致化疗疗效降低[1-2].放疗也能引起肿瘤细胞的MRP基因和MRP表达增强[3],但照射后肿瘤细胞MRP基因和MRP表达随时间的变化情况,目前少见报道.本研究采用体外培养的鼻咽癌CNE-1细胞株,检测照射前、后细胞MRP基因和MRP的表达随时间变化情况以及细胞对顺铂(DDP)敏感性的变化,从而探讨照射与鼻咽癌多药耐药性的关系.     

99Tcm-MIBI显像对肿瘤多药耐药检测的应用

MDR(多药耐药)是目前肿瘤化疗失败的主要原因,对MDR的检测可以帮助化疗决策的制定,从而使肿瘤患者得到更有效的治疗。99Tcm-MIBI(99Tcm-甲氧基异丁基异腈)是mdr1基因编码的P-gp(P-糖蛋白)和MRP(多药耐药相关蛋白)的转运底物,肿瘤细胞内99Tcm-MIBI摄取减低表明其P-gp的高表达,并与MRP的表达相关。因此,99Tcm-MIBI显像可在治疗前预测对化疗的反应,并为选择更有效的化疗策略提供依据。99m     

多药耐药相关基因在胃癌的表达

检测从未接受过化疗瓣胃癌病人胃癌组织及癌旁组织的酸性谷胱甘肽S－转移酶（GST－π）基因、多药耐药相关蛋白（MRP）基因、肺耐药蛋白（LRP）基因和多药耐药基因1（MDR1）。使用半定量逆转录聚合链酶反应（RT－PCR）方法。结果显示,在胃癌组织中,GST－π、MRP、LRP和MDR1表达阳性率分别为36.00%、12.00%、10.00%和10.00%,无显著高于癌旁组织中的表达,表达的总阳性率达46.00％。说明上述4种基因在未化疗过的胃癌组织中均有不同程度的高表达;但它们之间无共表达。近半数的胃癌病人可能存在固有性耐药。     

恶性黑色素瘤生物化疗的临床研究初探

目的 观察并比较Ⅲ、Ⅳ期恶性黑色素瘤患者应用生物化学治疗、生物治疗或化学治疗的近期和远期疗效.方法 分析82例Ⅲ、Ⅳ期恶性黑色素瘤患者化学治疗(顺铂、氮烯咪胺、吉西他滨),生物治疗(白介素2、干扰素α、树突状细胞疫苗)或生物化疗(上述两者结合)的临床疗效.其中生物化疗组32例、生物治疗组26例、化学治疗组24例.中位随访时间2年(1～4年).结果 近期疗效:生物化疗组有效率(RR)为71.9%,与生物治疗组(RR 46.2%)和化学治疗组(RR 54.2%)相比,有显著差异(P＜0.05).远期疗效:生物化疗组的中位生存时间(MST)为34个月,与生物治疗组(MST 26个月)和化学治疗组(MST 14个月)相比,有显著性差异(P＜0.05).各组的2年生存率分别为40.6%、38.5%和12.5%.生物化疗组毒副作用明显高于其他两组,但经一般处理,患者均可耐受.结论 细胞因子联合树突状细胞疫苗能明显提高接受化疗的恶性黑色素瘤患者治疗的有效率.     

^99Tc^m—MIBI显像对肿瘤多药耐药检测的应用

MDR（多药耐药）是目前肿瘤化疗失败的主要原因，对MDR的检测可以帮助化疗决策的制定，从而使肿瘤患得到更有效的治疗，^99Tc^m-MIBI^99Tc^m-甲氧基异丁基甲腈）是mdr1基因编码的P-gp(P-糖蛋白）和MRP（多药耐药相关蛋白）的转运底物，肿瘤细胞内^99Tc^m-MIBI摄取减低表明其P-gp的高表达，并与MRP的表达相关，因此，^99Tc^m-MIBI显像可在治疗前预测对化疗的反应，并为选择更有效的化疗策略提供依据。     

多药耐药基因表达与肺癌相关病理因素的关系

目的　探讨多药耐药基因 (MDR 1)表达与肺癌相关病理因素的关系。方法　应用逆转录—多聚酶链反应 (RT RCR)技术对 41例原发性肺癌 ,癌旁组织及 34枚淋巴结中MDR 1基因的表达进行检测分析。结果　肺癌组织及癌旁组织中MDR 1阳性率分别为 5 4%和 10 % ,两者比较具有显著性差异 (P <0 .0 0 1) ;转移淋巴结组织MDR 1阳性率为 5 3% ,而非淋巴结组织中未见MDR 1阳性表达 ;各病理类型中不同分化程度肿瘤的MDR 1阳性分布不同 ,低分化腺癌的MDR 1阳性率较高 (73 % )。术前化疗病例的MDR 1阳性率 (78% )高于未化疗者 (4 7% )。随访发现 ,MDR 1阳性患者肿瘤复发、转移的发生率 (5 0 % )高于MDR 1阴性者 (13 % )。结论　原发性肺癌组织中MDR 1基因表达增高 ,术前化疗可能起诱导作用 ;肺癌组织与其转移淋巴结中MDR 1表达具有一致性 ,MDR 1的阳性表达与肿瘤的大小 ,临床分型 ,TNM分期无明显关系 ,但可能提示肿瘤的恶性行为。     

缺氧诱导因子1α、多药耐药相关蛋白1在脊索瘤中的表达及其临床意义

目的探讨缺氧诱导因子1α(HIF-1α)蛋白、多药耐药相关蛋白1(MRP1)在脊索瘤中的表达水平及其与脊索瘤病理特征和放化疗抵抗之间的关系。方法收集2000年1月-2008年12月接受手术治疗的50例脊索瘤患者的肿瘤组织石蜡标本,另取15例骨软骨瘤标本作为对照。50例脊索瘤患者中男35例,女15例;年龄17～77岁,平均53.3岁;原发病例26例,复发病例24例;病理类型包括普通型48例,去分化型1例,外周型1例。采用免疫组化Envision法检测HIF-1α、MRP1蛋白表达情况,分析其与放化疗抵抗的关系,并探讨HIF-1α、MRP1表达与脊索瘤临床病理特征的关系。结果50例脊索瘤组织HIF-1α、MRP1的阳性表达率分别为80%和74%,均明显高于骨软骨瘤组织(分别为20%和27%,P<0.01)。相关性分析显示,脊索瘤组织中HIF-1α与MRP1的表达呈正相关关系(r=0.80,P<0.01)。脊索瘤组织中HIF-1α、MRP1的表达水平与患者性别、年龄、发病次数及肿瘤大小、部位、分化程度、分期、淋巴结转移均无明显关系。结论脊索瘤组织中HIF-1α和MRP1表达明显增高,且两者表达水平呈正相关,其过度表...     

实时荧光定量RT—PCR检测胃癌细胞中MRP2、MRP3及MRP5mRNA的表达

目的研究多药耐药相关蛋白2（MRP2）基因及MRP3、MRP5基因在正常胃细胞系GES-1、胃癌细胞株（BGC-823）及胃癌耐药细胞株BGC-823／ADM的表达差异,并探讨其在胃癌耐药中的意义。方法分别提取GES-1、BGC-823及BGC-823／ADM细胞的总RNA,逆转录cDNA,利用实时荧光定量PCR,根据标准品绘制标准曲线,检测MRP2、MRP3、MRP5基因的表达水平。结果MRP2基因在胃癌耐药细胞株BGC～823／ADM细胞中的表达量明显高于在胃癌细胞株（BGC-823）的表达,而与其在正常胃细胞系GES-1的表达没有显著性差异;MRP3、MRP5基因表达量在三种细胞中均有显著性差异。结论MRP2可能参与了胃癌的内在性耐药,而MRP3、MRP5可能与胃癌的获得性耐药有关,实时荧光定量方法是一种灵敏度高,特异性强,重复性好的定量检测方法。     

Tetrofosmin as predictors of tumour response.

Non-invasive imaging methods in the evaluation of chemotherapy response in malignant tumours are currently being explored. Standard Nuclear Medicine procedures seem to offer the clinician a promising tool in the management of those oncologic patients, who might benefit from chemotherapy. Early studies focused on the relationship between radionuclides used in tumour diagnosis and factors associated with multidrug resistance (MDR). The tumour expression of P-glycoprotein (Pgp) and multidrug resistance-related protein-1 expression (MRP) have been suggested as important factors in the failure of chemotherapy. Most studies found an association between Pgp levels and (99m)Tc-sestamibi ((99m)Tc-MIBI) or (99m)Tc-Tetrofosmin uptake ((99m)Tc-TF). Currently investigations in nuclear medicine oncology are focusing on the potential role of radionuclide imaging in the assessment of chemotherapy. Recent papers discuss the usefulness of radionuclides as (99m)Tc-MIBI and (99m)Tc-TF as non-invasive procedures to predict and to monitor therapy response in patients affected by malignant tumours treatable using chemotherapy. This chapter will review the latest development in (99m)Tc-TF, giving an overview of recent investigations carried out using this radiotracer in therapy oncology, with emphasis on its potential role as predictor of tumour response.     

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation 20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity.     

99mTc-MIBI imaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression.

In vitro studies have demonstrated that (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) is a transport substrate of multidrug resistance (MDR)-related proteins. The aim of this clinical study was to evaluate whether (99m)Tc-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and (99m)Tc-MIBI imaging to predict the clinical outcome. We also examined whether the scintigraphic parameters would help to distinguish the functional capacity of P-glycoprotein (Pgp) and MRP. METHODS: Twenty-four patients with a diagnosis of osteosarcoma were studied before neoadjuvant chemotherapy. Tumor-to-background ratios of both early (10 min) and delayed (1 h) images and the percentage washout rate (WR%) of (99m)Tc-MIBI were calculated. Immunohistochemical analysis of MRP and Pgp was performed on biopsy specimens, and the response to preoperative chemotherapy was assessed by histopathologic examination. RESULTS: Fifteen of 24 osteosarcoma samples in our series (62.5%) showed significant expression of MRP. The level of MRP expression was significantly correlated with the WR% of (99m)Tc-MIBI (r = 0.58, P = 0.003), and the WR% of (99m)Tc-MIBI was significantly faster in patients with high MRP expression than in those with a low MRP score (P = 0.007). The clearance rate of (99m)Tc-MIBI was significantly slower in tumor samples with negative or low expression of both Pgp and MRP (16% +/- 6.2%) when compared with osteosarcomas with high expression of both proteins (31.7% +/- 8.7%) (P = 0.001). There was not a significant difference between the WR% of (99m)Tc-MIBI in tumors with coexpression of both proteins and in tumors with high expression of either Pgp or MRP. Both the rate of MRP expression and the WR% of (99m)Tc-MIBI were significantly correlated with response rate. CONCLUSION: Our results suggest that the WR% of (99m)Tc-MIBI is correlated with MRP expression. Both the WR% of (99m)Tc-MIBI and MRP expression are correlated with therapy response. (99m)Tc-MIBI can be used as a general probe for functional imaging of both Pgp and MRP; however, it is not capable of differentiating the functional status of either MDR-related glycoprotein.     

In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.     

MSCT灌注成像对淋巴结转移瘤的鉴别诊断和疗效评价的临床研究

目的研究淋巴结转移瘤与肌肉CT灌注值的差异和相关性,并进行淋巴结转移瘤治疗前后比较。方法淋巴结转移瘤患者40例,测定淋巴结和相应层面肌肉的CT灌注值,其中部分淋巴结转移瘤病例于治疗后复查CT灌注值。结果转移性淋巴结与肌肉灌注值有显著差异,转移淋巴结治疗前与治疗后灌注值有显著差异。结论CT灌注成像法对淋巴结转移瘤的鉴别诊断及评价转移性淋巴结治疗效果和判断复发上具有临床应用价值。     

Role of ultrasound-guided core needle biopsy of axillary lymph nodes in the initial staging of breast carcinoma

OBJECTIVE: To evaluate the role of US-guided core biopsy in detection of metastatic axillary lymph nodes in preoperative staging of breast cancer. MATERIALS AND METHODS: US-guided core biopsy of suspicious axillary lymph nodes was performed in 39 patients with breast cancer. Biopsy results were compared to the axillary dissection results. Sensitivity, specificity and accuracy of the core biopsy in the detection of malignancy were calculated. RESULTS: Thirty-nine patients were assessed with biopsy; 30 patients were found to have metastatic carcinoma and nine had benign reactive hyperplasia. In 26 of 30 cases with biopsy-proven metastatic disease, there were malignant lymph nodes detected at axillary dissection. Four cases that had positive biopsy results and negative axillary dissection were accepted as complete response to chemotherapy. In three of nine cases with benign reactive hyperplasia, axillary dissection revealed metastatic disease. No significant complications were observed other than pain responding to analgesics. The sensitivity, specificity and accuracy of core biopsy in detection of malignancy were 90%, 100% and 92%, respectively. The results were statistically significant (p<0.001). CONCLUSION: Ultrasonographically detected lymph nodes can be easily assessed by US-guided biopsy. Core biopsy is a reliable and easily performed method without significant complications.     

Lack of correlation between Tc-99m-sestaMIBI uptake and cadherin expression in infiltrating ductal breast carcinoma as prognostic indicators

Despite using various kinds of prognostic indicators, it is still not possible to predict the biological behavior of breast cancer in all patients. Tc-99m-sestaMIBI (MIBI) uptake determined by breast scintigraphy and cadherin expression of tumor tissue revealed by immunohistochemistry are suggested as potential agents for this purpose. We hypothesize that there can be a correlation between MIBI whose cellular mitochondrial content is claimed to play a significant role in its tumor uptake and cadherin whose downregulation causes an increase in mitochondrial activity in human mammary carcinoma cell lines. The aim of this study was to assess the relationship between the degree of MIBI tumor uptake and cadherin expression in infiltrating ductal breast carcinoma. Correlation with response to chemotherapy and some known prognostic factors of breast cancer such as tumor size, number of metastatic axillary lymph nodes and microscopic grading was also done. Fourteen patients who underwent scintimammography and subsequent surgical excisional biopsy that revealed infiltrating ductal carcinoma were enrolled in this study. Statistical analysis did not show any correlation between MIBI uptake and cadherin expression (p > 0.05). Also, no statistically significant correlation was noted between MIBI uptake and tumor size, number of metastatic lymph nodes, microscopic grade, stage of the disease or response to chemotherapy. Similarly, there was no statistically significant correlation between cadherin expression and tumor size, number of metastatic lymph nodes, microscopic grade, stage of the disease or chemotherapy response. The results of this study imply that there is no correlation between MIBI tumor uptake and cadherin expression with neither of them good enough to be used as prognostic indicators for breast cancer.