博宁联合化疗治疗骨转移癌的疗效分析

目的 :分析单纯化疗与博守联合化疗对实体瘤骨转移引起疼痛治疗的效果。方法 :42例病人随机分为单纯化疗组和化疗联合博宁组 ,对疼痛缓解程度和活动能力改善等进行对照研究。结果 :化疗联合应用博宁组疼痛缓解率及肿瘤变化方面明显优于单纯联合化疗组 (P <0 .0 5 ) ,而在活动能力改善方面则无明显差别。结论 :博宁联合化疗治疗骨转移癌引起的疼痛效果优于单纯联合化疗     

Synthetic Route to a Benzooxazole Derivative with Heparanase Inhibitory Activity

The synthesis of a benzooxazol-5-yl acetic acid derivative (9) with strong heparanase and angiogenesis inhibitory activity, and thus possible commercial interest, is described in detail.     

基于免疫磁性纳米球快速高效准确检测淋巴结转移癌细胞

发展了一种基于免疫磁性纳米球(IMNs)快速、高效、准确检测淋巴结转移癌细胞(LNMCCs)的策略.首先利用本课题组发展的方法制备了具有磁性和生物靶向双功能的IMNs,然后利用IMNs通过免疫磁分选对淋巴结转移癌病人淋巴结穿刺物中的LNMCCs进行分离和富集,最后采用瑞氏染色法和免疫细胞化学(ICC)对富集的LNMCCs进行鉴定,实现对LNMCCs的快速高效准确检测.免疫磁分选实现了LNMCCs的分离和富集,可以有效降低淋巴结穿刺物中的背景干扰;瑞氏染色法和ICC鉴定为准确诊断提供了更多可靠依据,因此,传统细胞学敏感性、特异性和诊断准确率不高的问题得到明显改善.其次,淋巴结穿刺物与IMNs的孵育只需5 min,简便快速,完整保留了LNMCCs的形态学特征,为淋巴结转移癌(LNMC)的分类和后续病理学分析提供了重要基础.此外,IMNs对淋巴结穿刺物中上皮来源癌细胞的特异性捕获可以确诊捕获的细胞为LNMCCs,实现了LNMC和恶性淋巴瘤的鉴别诊断.最后,采用本方法检测了110例病人淋巴结穿刺物中的LNMCCs,总诊断准确率高达98.2%,特异性为100.0%,敏感性为98.0%,相比于传统细胞学诊断都有明显的提高.因此,IMNs用于LNMC病人淋巴结穿刺物中LNMCCs的检测是一次新的尝试,为LNMC的诊断和研究提供了新思路.     

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

Objective

To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.

Methods

Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.

Results

Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.

Conclusion

Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.     

The mechanical problems in tumor and tumor microenvironment

肿瘤微环境包括肿瘤细胞、间质细胞、细胞外基质等.其在肿瘤的生长和发展过程中起着关键作用.肿瘤的微环境与正常组织的微环境有着显著的不同.肿瘤中的压应力对微环境有着多方面的影响, 例如, 可调控血管与淋巴管的功能, 造成代谢异常和间质高压, 压缩间隙基质, 增大药物输运的困难, 促进间质细胞变异并诱导肿瘤细胞转移. 因此, 肿瘤中的力学因素引起了广泛关注.本文总结了肿瘤及其微环境力学问题的研究进展, 讨论了肿瘤微环境中应力产生、药物输运、肿瘤转移等问题, 介绍了肿瘤微环境正常化的策略及其对肿瘤治疗的意义.     

Imaging‐Guided Combined Photothermal and Radiotherapy to Treat Subcutaneous and Metastatic Tumors Using Iodine‐131‐Doped Copper Sulfide Nanoparticles

Combining different therapeutic strategies to treat cancer by overcoming limitations of conventional cancer therapies has shown great promise in both fundamental and clinical studies. Herein, by adding ¹³¹I when making iodine‐doped CuS nanoparticles, CuS/[¹³¹I]I nanoparticles are obtained, which after functionalization with polyethylene glycol (PEG) are used for radiotherapy (RT) and photothermal therapy (PTT), by utilizing their intrinsic high near‐infrared absorbance and the doped ¹³¹I‐radioactivity, respectively. The combined RT and PTT based on CuS/[¹³¹I]I‐PEG is then conducted, achieving remarkable synergistic therapeutic effects as demonstrated in the treatment of subcutaneous tumors. In the meanwhile, as revealed by bimodal nuclear imaging and computed tomography (CT) imaging, it is found that CuS/[¹³¹I]I‐PEG nanoparticles after being injected into primary solid tumors could migrate to and retain in their nearby sentinel lymph nodes. Importantly, the combined RT and PTT applied on those lymph nodes to assist surgical resection of primary tumors results in remarkably inhibited cancer metastasis and greatly prolonged animal survival. In vivo toxicology studies further reveal that our CuS/I‐PEG is not obviously toxic to animals at fourfold of the treatment dose. This work thus demonstrates the potential of combining RT and PTT using a single nanoagent for imaging‐guided treatment of metastatic tumors.     

Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1α levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.     

纵隔神经内分泌癌的肾小球内转移

报告一例十分罕见的肾小球内癌转移病例。肾活检标本进行了光镜、免疫荧光、免疫组化及透射电镜检查。组织学观察,肾小球毛细血管内异常细胞堆积。免疫荧光结果：异常细胞IgG,IgA,IgM,C3,C1q,FRA,ALb,κ链及λ链均阴性。免疫组化染色异常细胞LCA及F8阴性,chrmogranin阳性。电镜观察异常细胞胞质内含特征性的致密核心颗粒。病理诊断神经内分泌癌肾小球内转移。上述结果显示,电镜检查及免疫组织化学方法对本例有诊断意义。