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91.
Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases 总被引:4,自引:0,他引:4
Holger Palmedo Stefan Guhlke Hans Bender Johannes Sartor Georg Schoeneich Jörn Risse Frank Grünwald F.F. Russ Knapp Jr. Hans-Jürgen Biersack 《European journal of nuclear medicine and molecular imaging》2000,27(2):123-130
The aim of this study was to determine the maximum tolerated dose of rhenium-188 hydroxyethylidene diphosphonate (HEDP) in
prostate cancer patients with osseous metastases who are suffering from bone pain. Twenty-two patients received a single injection
of escalating doses of carrier-added 188Re-HEDP [1.3 GBq (35 mCi), 2.6 GBq (70 mCi), 3.3 GBq (90 mCi) and 4.4 GBq (120 mCi)]. Blood counts and biochemical parameters
were measured weekly over a period of 8 weeks. Haematological toxicity (WHO grading) of grade 3 or 4 was considered unacceptable.
Clinical follow-up studies including methods of pain documentation (medication, pain diary) were performed for 6 months after
treatment. In the 1.3-GBq group, no haematological toxicity was observed. First haematotoxic results were noted in those patients
with a dose of 2.6 GBq 188Re-HEDP. In the 3.3-GBq group, one patient showed a reversible thrombopenia of grade 1, one a reversible thrombopenia of grade
2 and three a reversible leukopenia of grade 1. In the 4.4-GBq group, thrombopenia of grades 3 and 4 was observed in one and
two patients (baseline thrombocyte count <200×109/l), respectively, and leukopenia of grade 3 was documented in one patient. The overall nadir of thrombopenia was at week
4. The individual, maximum percentage decrease in thrombocytes in the 1.3-, 2.6-, 3.3- and 4.4-GBq groups was 17%, 40%, 60%
and 86%, respectively. In two patients, a transient increase in serum creatinine was observed (max. 1.6 mg/dl). Pain palliation
was reported by 64% of patients, with a mean duration of 7.5 weeks. The response rate seemed to increase with higher doses,
reaching 75% in the 4.4-GBq group. It is concluded that in prostate cancer patients, the maximum tolerated dose of 188Re-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200×109/l. In patients with thrombocyte counts significantly above 200×109/l, a dose of 4.4 GBq might be tolerable. Thrombo- and leukopenia are the most important side-effects. Pain palliation can
be achieved in 60%–75% of patients receiving a dose of 2.6 GBq or more of 188Re-HEDP. Studies in a larger patient population are warranted to evaluate further the palliative effect of 188Re-HEDP.
Received 7 July and in revised form 6 October 1999 相似文献
92.
Chun-Hui Su Bor-Tsung Hsieh Stephen-Wan Leung Chiung-Jen Wu Sheng-Yi Chiu 《International journal of radiation biology》2013,89(10):707-716
Purpose: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-κB) in neointimal hyperplasia following intracoronary irradiation.Materials and methods: Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, β-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 (188Re) β-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination.Results: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy 188Re β-irradiation, respectively. The expression of arterial NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-κB p65 expression in both gene and protein levels, and such induction could be significantly reduced by 188Re β-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the β-irradiation could not be observed in ICAM-1 and VCAM-1.Conclusion: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-κB p65. 相似文献
93.
《Hemoglobin》2013,37(2):85-102
Acute chest syndrome (ACS) is the most common cause of death in patients with sickle cell anemia. Its management is primarily palliative. We performed a Phase I evaluation of purified poloxamer 188 (a non‐ionic surfactant) in the management of ACS. Forty‐three patients with sickle cell disease and ACS were treated with doses as high as 2960 mg/day by continuous intravenous (IV) infusion. The maximum tolerated dose has not been identified. No evidence of renal toxicity or other limiting adverse events were found. One adult patient died due to sepsis and adult respiratory distress syndrome, which were unrelated to treatment. Poloxamer 188 is safe to administer to patients with ACS, and preliminary data suggest that it may shorten its duration and the length of hospitalization in a dose related manner. Children appeared to benefit more than adults. The data and safety profile justify further studies with purified poloxamer 188 in the treatment of ACS. 相似文献
94.
Kelly RF Hursey TL Patel RB Parrillo JE Schaer GL 《Journal of thrombosis and thrombolysis》1998,5(3):239-247
Poloxamer 188 is a surfactant with hemorheological, antithrombotic, and neutrophil-inhibitory properties. This agent has been demonstrated to reduce infarct size and to improve left ventricular function in animal models of myocardial infarction and reperfusion, and recently in a randomized trial of patients receiving thrombolytic therapy for acute myocardial infarction. In addition to reducing reperfusion injury, poloxamer 188 might be beneficial by increasing collateral blood flow. The purpose of this study was to determine the effect of poloxamer 188 on collateral blood flow, myocardial infarct size, and left ventricular function in a canine model of prolonged (3 hours) coronary occlusion and reperfusion. Closed-chest dogs (n = 21) underwent a 3-hour coronary occlusion and 3 hours of reperfusion. At 1 hour of occlusion, dogs received poloxamer 188, 75 mg/kg IV bolus, followed by 150 mg/kg/h IV for the final 2 hours of coronary occlusion and throughout reperfusion, or a saline placebo. Regional myocardial blood flow was measured using colored microspheres. Myocardial infarct size and area at risk were determined by postmortem histochemical staining. Compared with controls, poloxamer 188–treated dogs showed no significant increase in collateral blood flow during the final 2 hours of a 3-hour coronary artery occlusion. In addition, poloxamer 188 treatment had no beneficial effect on infarct size or left ventricular function in this model. Increased collateral blood flow is unlikely to be a beneficial mechanism of poloxamer 188 in myocardial infarction. These data also question the benefit of this agent to reduce reperfusion injury in the setting of more prolonged (3-hour) coronary occlusion. 相似文献
95.
Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review 总被引:4,自引:1,他引:4
Ibrahim SM Lewandowski RJ Sato KT Gates VL Kulik L Mulcahy MF Ryu RK Omary RA Salem R 《World journal of gastroenterology : WJG》2008,14(11):1664-1669
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. The majority of patients with HCC present with unresectable disease. These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies. Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses, limiting the use of external beam radiation. Because of these limitations, novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization) represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused, these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles. Embedded within the arterioles, the ^90y.impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor. Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight two currently available radioembolic devices ^90Y, ^188Rh) and provide the reader with a recent review of the literature. 相似文献
96.
97.
Yuhua S Ligen L Jiake C Tongzhu S 《Burns : journal of the International Society for Burn Injuries》2012,38(1):95-101
Objective
To discuss the effect of Poloxamer 188 (P188) on deepening of deep second-degree burn wounds in the early stage after burn.Methods
We divided Wistar rats with deep second-degree burn wounds on the backs thereof into two groups, then intravenously injected P188 for the treatment group and intravenously injecting physiological saline for the control group, detecting the activity of Na+–K+–adenosine triphosphatase (Na+–K+–ATPase), myeloperoxidase (MPO) and the content of malonaldehyde (MDA) and succinic dehydrogenase (SDH) in the burn wound, and showing the degree of necrosis in the wound by haematoxylin–eosin (HE) and proliferating cell nuclear antigen (PCNA) immunohistochemical staining.Results
In the control group and treatment group, the activity of SDH and Na+–K+–ATPase dropped to the lowest point 24 h after the burn took place, and then increased gradually, but was still far lower than the normal level at the furthest time point. At 24 h after burn, activity of SDH and Na+–K+–ATPase in the treatment group was higher than that of the control group (P < 0.05); the activity of MPO of the control group reached the highest point at 24 h while that of MPO of the treatment group reached the highest point after 48 h; later, that of MPO of both groups decreased, but was still higher than the normal level. Compared with the highest values of the activity of MPO of both groups, that of the control group was higher than that of the treatment group (p < 0.05); the contents of MDA of both groups kept increasing after the burn; 72 h later, that of the control group was higher than that of the treatment group (p < 0.05). HE and PCNA staining showed progressive damage of the wound in the treatment group, which was decreased with treatment, particularly at the early stages.Conclusion
Systemic application of P188 on deep second-degree burn wounds at the early stage may alleviate wound deepening, whose mechanism may be related to timely sealing up the damaged cell membrane and inhibiting the inflammatory reaction. 相似文献98.
miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression
Hongtuan Zhang Shiyong Qi Tao Zhang Andi Wang Ranlu Liu Jia Guo Yuzhuo Wang Yong Xu 《Oncotarget》2015,6(8):6092-6104
Elucidation of the molecular targets and pathways regulated by the tumour-suppressive miRNAs can shed light on the oncogenic and metastatic processes in prostate cancer (PCa). Using miRNA profiling analysis, we find that miR-188-5p was significantly down-regulated in metastatic PCa. Down-regulation of miR-188-5p is an independent prognostic factor for poor overall and biochemical recurrence-free survival. Restoration of miR-188-5p in PCa cells (PC-3 and LNCaP) significantly suppresses proliferation, migration and invasion in vitro and inhibits tumour growth and metastasis in vivo. We also find overexpression of miR-188-5p in PC-3 cells can significantly enhance the cells'' chemosensitivity to adriamycin. LAPTM4B is subsequently identified as a direct target of miR-188-5p in PCa, and is found to be significantly over-expressed in PCa. Knockdown of LAPTM4B phenotypically copies miR-188-5p-induced phenotypes, whereas ectopic expression of LAPTM4B reverses the effects of miR-188-5p. We also find that restoration of miR-188-5p can inhibit the PI3K/AKT signaling pathway via the suppression of LAPTM4B. Taken together, this is the first report unveils that miR-188-5p acts as a tumour suppressor in PCa and may therefore serve as a useful therapeutic target for the development of new anticancer therapy. 相似文献
99.
100.
【摘要】 目的 探讨miRNA-188-5p(miR-188-5p)在皮肤鳞状细胞癌(鳞癌)组织和细胞中的表达,分析其表达下调对皮肤鳞癌细胞增殖和侵袭能力的影响。方法 2012年11月至2018年10月在河南省新乡医学院第一附属医院收集50例手术切除的皮肤鳞癌组织及50例癌旁正常皮肤组织。实时荧光定量PCR(qPCR)检测皮肤鳞癌组织、癌旁正常皮肤组织、皮肤鳞癌细胞系SCL-1、A431、HSC-5和人永生化角质形成细胞株HaCaT细胞中miR-188-5p的表达。培养的A431和HSC-5细胞分别分为2组:miR-188-5p抑制剂组和阴性对照组,对转染miR-188-5p抑制剂的细胞和阴性对照组细胞,通过qPCR检测miR-188-5p的相对表达(2-△△Ct),并以CCK8法和Transwell小室分别检测各组细胞的增殖活性和侵袭能力。双荧光素酶报告实验检测miR-188-5p和PTEN的相互作用,Western印迹法检测PTEN、总Akt(t-Akt)和磷酸化Akt(p-Akt)的表达。两独立样本比较采用t检验。结果 皮肤鳞癌组织中miR-188-5p的相对表达(5.213 ± 3.138)显著高于癌旁正常皮肤组织(1.010 ± 0.364,t = 9.187,P < 0.001)。SCL-1、A431和HSC-5细胞中miR-188-5p的表达(3.858 ± 0.163、7.068 ± 0.262和4.572 ± 0.413)均显著高于HaCaT细胞(1.079 ± 0.300,t = 17.890、21.110和8.737,均P < 0.05)。与阴性对照组相比,miR-188-5p抑制剂组A431和HSC-5细胞miR-188-5p表达显著下调(均P < 0.01),细胞增殖和侵袭能力下降(均P < 0.05)。双荧光素酶报告实验显示,miR-188-5p表达下调显著上调A431和HSC-5细胞中PTEN的表达,但抑制p-Akt的表达。结论 miR-188-5p在皮肤鳞癌组织和细胞中高表达,且miR-188-5p表达下调可能通过调控PTEN/Akt途径,抑制皮肤鳞癌细胞增殖活性和侵袭能力。 相似文献