-
Shi Ke,
Wei Wang,
Xiuchun Qiu, Fujun Zhang,
Jason T Yustein,
Arlin G Cameron,
Siyuan Zhang,
Dihua Yu,
Chaoxia Zou,
Xu Gao,
Jie Lin,
Sasidhar Yallampalli,
Min Li
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer is a heterogenetic tumor at the cellular level with multiple factors and components. The inconsistent expression of molecular markers during disease progression reduces the accuracy of diagnosis and efficacy of target-specific therapy. Single target-specific imaging agents can only provide limited tumor information at one time point. In contrast, multiple target-specific imaging agents can increase the accuracy of diagnosis. The aim of this study was to demonstrate the ability of multi-agent imaging to discriminate such differences in single tumor. Mice bearing human cancer cell xenografts were tested to determine individual differences under optimal experimental conditions. Neovasculature agent (RGD peptide), tumor stromal agent (matrix metalloproteinase), and tumor cell markers (epidermal growth factor, Her-2, interleukin 11) imaging agents were labeled with reporters. 18F-Fluorodeoxyglucose was used to evaluate the tumor glucose status. Optical, X-ray, positron emission tomography, and computer tomography imaging modalities were used to determine tumor characteristics. Tumor size and imaging data demonstrated that individual differences exist under optimal experimental conditions. The target-specific agents used in the study bind to human breast cancer cell lines in vitro and xenografts in vivo. The pattern of binding corresponds to that of tumor markers. Multi-agent imaging had complementary effects in tumor detection. Multiple noninvasive imaging agents and modalities are complementary in the interrogation of unique biological information from each individual tumor. Such multi-agent approaches provide methods to study several disease components simultaneously. In addition, the imaging results provide information on disease status at the molecular level.
Current Molecular Medicine 01/2013; · 5.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomography (CT)-guided interstitial (125)I seed implantation with traditional radiochemotherapy for treatment of recurrent gliomas.
The response rate at 1, 3, 6 and 12 months after (125)I seed implantation was 68.6, 74.3, 77.1 and 62.8% respectively, which was significantly higher than the group treated with the conventional chemoradiation protocol (p < 0.05). Patients exposed to (125)I seed implantation had a median survival of 29.0 months, whereas the median survival of those treated with traditional radiochemotherapy was 19.0 months. The difference observed between the two groups was significant. There were no severe complications or mortality associated with either treatment, except for one case of intracerebral hemorrhage around the tumor area in the (125)I seed implants group.
From November 2002 to May 2010, 73 consecutive patients with recurrent gliomas were treated with CT-guided (125)I seed implantation (35 cases) or traditional radiochemotherapy (38 cases). Patients were followed up after treatment and the therapeutic effect was evaluated by comparing the response and survival rates of the two groups. In particular, patients treated with (125)I seed implantation were monitored for adverse side effects.
CT-guided (125)I seed implantation is safe and well-tolerated and more importantly, shows superior efficacy compared with conventional radiochemotherapy. This suggests that CT-guided (125)I seed implantation could be an alternative approach for recurrent gliomas.
Cancer biology & therapy 08/2012; 13(10):840-7. · 2.64 Impact Factor
-
Wei Wang,
Jie Lin,
Sushovan Guha,
Zhimin Tong,
Arlin G Cameron, Fujun Zhang,
Xiuchun Qiu,
Chaoxia Zou,
Xu Gao,
Michel E Mawad,
Shi Ke
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to develop target-specific binding agents for in vitro and in vivo imaging of human pancreatic cancer.
A monoclonal neutrophil gelatinase-associated lipocalin (NGAL)-specific antibody and a peptide specific for matrix metalloproteinase (MMP) were labeled with a near-infrared dye for in vitro and in vivo imaging studies. Fluorescence or confocal microscopy was used to determine antibody or peptide binding and internalization of agents into human AsPC-1, Panc-1, and MiaPaCa pancreatic cancer cell lines and in mice bearing ectopic or orthotopic pancreatic tumor transplants.
Both the NGAL-specific antibody and MMP peptide bound to pancreatic cancer cells with high specificity; most NGAL-specific antibody localized to the cytosol. In vivo imaging results demonstrated high signal intensity of both agents bound to the tumor. The average tumortr-to-background ratio of antibody and peptide was 1.29 and 2.86, respectively. Signal was also detectable in the liver, kidneys, and bladder.
Both NGAL-specific antibody and MMP peptide bound to cancer cells, and the labeled antibody was internalized. These results demonstrate that both agents can be used to enhance detection of human pancreatic cancer xenografts. However, the biodistribution patterns of these agents might limit their use in research and clinical practice.
Pancreas 07/2011; 40(5):689-94. · 2.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Developing agents with 'seek, treat and see' capability is critical for personalized molecular medicine. Those agents will specifically target the disease markers for diagnosis and apply the biologically effective dose for treatment. Retinoids regulate a multitude of biological processes. In addition, retinoic acid can reverse premalignancy, significantly decrease second primary tumors and provide a treatment benefit in head and neck, lung, esophagus, colon and bladder cancer. These data suggest that cancer cells can take up retinoids. Therefore, retinoids are potential tumor-imaging agents. We developed near-infrared (NIR)-labeled retinoid agents to detect human cancers, visualize drug redistribution within the body, determine the optimal biological dose and reduce systemic toxicity. Our data demonstrate that the retinoid agent, but not the free dye, binds to the human tumor cells and is internalized, where it permits the imaging of human cancer xenografts. The high dose of retinoid agent is significantly associated with systemic toxicity. In summary, synthetic NIR-labeled retinoid agents can be used to detect multiple human cancer xenografts as the agent is internalized by cancer cells. The binding of the agent to the tumor xenografts is dependent on the redistribution of the agent. Therapeutic agents labeled with reporters will interrogate tumor-drug interactions and permit analysis of biodistribution, pharmacokinetics and pharmacodynamics in real time. At the same time, we can apply the biologically effective dose for therapy, instead of the traditional maximum tolerated dose, to reduce systemic toxicity.
Contrast Media & Molecular Imaging 07/2011; 6(4):200-8. · 3.33 Impact Factor
-
Cancer 06/2011; 117(12):2822-3. · 4.77 Impact Factor
-
Xin Li,
Weijun Fan,
Liang Zhang,
Ming Zhao,
Zilin Huang,
Wang Li,
Yangkui Gu,
Fei Gao,
Jinhua Huang,
Chuanxing Li, Fujun Zhang,
Peihong Wu
[show abstract]
[hide abstract]
ABSTRACT: Microwave ablation has recently been developed as a safe and effective treatment for a variety of tumors. The authors evaluated the safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation of adrenal malignant tumors.
Nine patients between 41 and 83 years of age (average age, 54 years) with adrenal carcinoma (a total of 10 lesions) received CT-guided percutaneous water-cooled microwave ablation. The 9 cases included 1 primary adrenocortical carcinoma and 8 metastatic carcinomas (4 from lung cancer, 2 from hepatocellular carcinoma, 1 from intrahepatic cholangiocarcinoma, and 1 from left tibial osteosarcoma). Of the 8 metastatic cases, 7 were unilateral, and 1 was bilateral. All cases were pathologically confirmed by aspiration biopsy or postsurgical biopsy. The tumor diameters ranged from 2.1 cm to 6.1 cm (average, 3.8 cm). The average number of ablation sites was 1.5 sites (1-3 sites), and the average accumulated ablation time was 7.7 minutes (4-15 minutes). The procedures were performed using a cooled-shaft antenna.
The patients were followed for 3-37 months, with an average of 11.3 months. Nine of 10 lesions were completely necrotized after first treatment. The other lesion was completely necrotized after 2 treatments. One of the patients experienced hypertensive crisis during treatment. No patient experienced recurrent tumor at the treated site, and this lack of recurrence indicated effective local control. All patients had progression of metastatic disease at extra-adrenal sites.
CT-guided percutaneous water-cooled microwave ablation is a minimally invasive and effective method for the treatment of adrenal carcinoma.
Cancer 04/2011; 117(22):5182-8. · 4.77 Impact Factor
-
Xin Li,
Weijun Fan MD,
Liang Zhang,
Ming Zhao,
Zilin Huang,
Wang Li,
Yangkui Gu,
Fei Gao,
Jinhua Huang,
Chuanxing Li, Fujun Zhang,
Peihong Wu MD
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND:Microwave ablation has recently been developed as a safe and effective treatment for a variety of tumors. The authors evaluated the safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation of adrenal malignant tumors.METHODS:Nine patients between 41 and 83 years of age (average age, 54 years) with adrenal carcinoma (a total of 10 lesions) received CT-guided percutaneous water-cooled microwave ablation. The 9 cases included 1 primary adrenocortical carcinoma and 8 metastatic carcinomas (4 from lung cancer, 2 from hepatocellular carcinoma, 1 from intrahepatic cholangiocarcinoma, and 1 from left tibial osteosarcoma). Of the 8 metastatic cases, 7 were unilateral, and 1 was bilateral. All cases were pathologically confirmed by aspiration biopsy or postsurgical biopsy. The tumor diameters ranged from 2.1 cm to 6.1 cm (average, 3.8 cm). The average number of ablation sites was 1.5 sites (1-3 sites), and the average accumulated ablation time was 7.7 minutes (4-15 minutes). The procedures were performed using a cooled-shaft antenna.RESULTS:The patients were followed for 3-37 months, with an average of 11.3 months. Nine of 10 lesions were completely necrotized after first treatment. The other lesion was completely necrotized after 2 treatments. One of the patients experienced hypertensive crisis during treatment. No patient experienced recurrent tumor at the treated site, and this lack of recurrence indicated effective local control. All patients had progression of metastatic disease at extra-adrenal sites.CONCLUSIONS:CT-guided percutaneous water-cooled microwave ablation is a minimally invasive and effective method for the treatment of adrenal carcinoma. Cancer 2011;. © 2011 American Cancer Society.
Cancer 04/2011; 117(22):5182 - 5188. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate (125)I seed brachytherapy combined with sorafenib in the treatment of patients with multiple lung metastases after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).
From July 2006 to December 2009, eight patients with multiple lung metastases after OLT for HCC underwent (125)I brachytherapy combined with sorafenib, and laboratory and radiologic examinations were performed before and after the treatment. Changes in symptoms and survival time were noted at follow-up.
The follow-up time ranged from 14 to 37 months. The local control rates of multiple lung metastases after OLT for HCC after 4, 6, 12, 18 and 24 months were 92.2, 82.4, 76.2, 73.3 and 72.2%, respectively. Four patients died (survival time 14, 15, 25 and 37 months, respectively), and four patients are alive at the time of this writing (follow-up time 18, 21, 26 and 30 months, respectively). The overall 1-, 2- and 3-year survival rates were 100, 50 and 12.5%, respectively. The median survival time was 21 months. Procedure-related complications were minimal.
(125)I brachytherapy combined with sorafenib is safe, feasible and promising approach in the treatment of patients with multiple lung metastases after OLT for HCC, but large-scale randomized clinical trials are necessary for confirmation.
Journal of Cancer Research and Clinical Oncology 11/2010; 136(11):1633-40. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to evaluate high-intensity focused ultrasound (HIFU) ablation combined with transcatheter arterial chemoembolisation (TACE) in the treatment of larger hepatocellular carcinoma (HCC). Eighty-nine (89) patients with unrespectable larger HCC were randomised into a TACE group (n=45) and a TACE plus HIFU group (n=44). Therapeutic effects were assessed at follow-up with physical examination, level of serum alpha-fetoprotein and computed tomography or magnetic resonance imaging. All patients were followed up to observe long-term therapeutic effects and evaluated prognostic factors for survival. No severe complication was observed. Follow-up images showed that total effective rate in tumour response accounted for 72.8% in the TACE-HIFU group, which were significantly higher than that of TACE group (44.5%, P<0.05). The 1-, 2-, 3- and 5-year overall survival rates for the TACE-HIFU group were 72.7%, 50.0%, 31.8% and 11.4%, respectively; correspondingly, for the TACE group were 47.2%, 16.7%, 2.8% and 0%, respectively (P<0.01). The 1-, 2-, 3- and 5-year disease-free survival rates for the TACE-HIFU group were 34.1%, 18.2%, 9.1% and 0%, respectively; correspondingly, for the TACE group were 13.9%, 5.6%, 0% and 0%, respectively (P<0.01). TNM stage, portal vein tumour thrombosis and Child-Pugh classification each had a significant effect on the survival. HIFU ablation combined with TACE is safe, effective and a promising approach for the treatment of larger HCC.
European journal of cancer (Oxford, England: 1990) 09/2010; 46(13):2513-21. · 4.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: High-intensity focused ultrasound (HIFU) is a new, noninvasive technique with potential to ablate and inactivate tumors. Treatment of solid tumors with HIFU has been reported. In this study, the safety and effects of HIFU in the clinical therapy of malignant bone tumors were assessed.
Biochemical markers and magnetic resonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT) were used to evaluate 25 patients with malignant bone tumors before and after HIFU treatment.
HIFU resulted in significant improvement in biochemical markers, and no severe complications were observed. After HIFU treatment, 21 (87.5%) patients were completely relieved of pain, and 24 (100%) experienced significant relief. On the basis of MRI or PET-CT, HIFU was effective: For patients with primary bone tumors, 6 (46.2%) had a complete response, 5 (38.4%) had a partial response, 1 (7.8%) had a moderate response, and 1 suffered progressive disease; the response rate was 84.6%. For patients with metastatic bone tumors, 5 (41.7%) had complete response, 4 (33.3%) had partial response, 1 (8.3%) had a moderate response, 1 (8.3%) had stable disease, and 1 suffered progressive disease; the response rate was 75.0%. The 1-, 2-, 3-, and 5-year survival rates were 100.0%, 84.6%, 69.2%, and 38.5%, respectively, for patients with primary bone tumors and 83.3%, 16.7%, 0%, and 0%, respectively, for patients with metastatic bone tumors. The survival rates for patients with primary bone tumors were significantly better than for those with metastatic tumors.
HIFU safely and noninvasively ablated malignant bone tumors and relieved pain. HIFU ablation should be further investigated, as it appears to be successful in the treatment of primary malignant bone tumors.
Cancer 08/2010; 116(16):3934-42. · 4.77 Impact Factor
-
Dechao Jiao,
Linxue Qian,
Yanling Zhang, Fujun Zhang,
Chuanxing Li,
Zilin Huang,
Liang Zhang,
Weidong Zhang,
Peihong Wu,
Xinwei Han,
Guangfeng Duan,
Jianjun Han
[show abstract]
[hide abstract]
ABSTRACT: To evaluate effects of microwave ablation with a 2,450-MHz internally cooled-shaft antenna in animal experiments and in a clinical study.
Microwave ablation was performed using a cooled-shaft antenna in eight in vivo (36 ablations) porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Sixty patients (44 men, 16 women; mean age 53 years) with 96, 1-8 cm (mean 3.20 +/- 0.17 cm) liver cancers were treated with the same microwave ablation technique. Complete ablation (CA), local tumor progression (LTP) rates and complications were determined.
In vivo livers, short axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60-W group R(2) = 0.76, 80-W group R(2) = 0.87), with a relative plateau achieved within 10 min for power settings of 60 or 80 W. Within 10 min in the 60 and 80-W groups, respectively, 89 and 85.76% of maximum short axis diameter were achieved. CA rates in small (3.0 cm), intermediate (3.1-5.0 cm) and large (5.1-8.0 cm) liver cancers were 96.43% (54/56), 92.31% (24/26) and 78.57% (11/14), respectively. During a mean follow-up period of 17.17 +/- 6.52 months, LTP occurred in five (5.21%) treated cancers. There was no significant difference in the CA and LTP rate between the HCC and liver metastasis patient subgroups (P > 0.05).
The short axis diameter enlargement has a relative plateau within 10 min by fixing power output to 60 or 80 W, using the 2,450-MHz internally cooled-shaft antenna in vivo porcine livers. Effective local tumor control was achieved during one microwave ablation session.
Journal of Cancer Research and Clinical Oncology 02/2010; 136(10):1507-16. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to evaluate the effectiveness of ultrasonographically guided high-intensity focused ultrasound (HIFU) ablation for superficial malignant tumors. HIFU ablation was applied to 38 cases. The diameter of tumors ranged from 1.5-18 cm, including < or =3 cm in seven cases, >3 to < or =5 cm in four cases, >5 to <10 cm in 15 cases, and > or =10 cm in 12 cases. Using imaging techniques, the volume and activity of tumors were observed before and after HIFU ablation, and the effectiveness of HIFU ablation in superficial malignant tumors was evaluated. For tumors < or =5 cm in diameter, HIFU ablation was completely effective in 100% (11/11) of cases; for tumors >5 cm in diameter, HIFU ablation was completely effective in 25.9% (7/27) of cases, partially effective in 14.8% (4/27) of cases, moderately effective in 33.3% (9/27) of cases; the disease remained stable in 14.8% (4/27) of cases and progressed in 11.1% (3/27) of cases. No significant difference was observed in the tumor volumes before (202.6 +/- 230.4 cm(3)) and 6-8 w after HIFU ablation (188.1 +/- 215.8 cm(3)). However, the difference in the active volume before (202.6 +/- 230.4 cm(3)) and after (127.6 +/- 189.7 cm(3)) HIFU ablation was statistically significant. Among 38 the cases, 32 reported painful symptoms, with a pain score of 4.39 +/- 2.36, before the ablation; the values dropped to 0.19 +/- 0.54 after HIFU, and the difference was statistically different. Thus, HIFU is a safe, effective and promising approach for the treatment of superficial malignant tumors.
Cancer biology & therapy 12/2009; 8(24):2398-405. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to prospectively evaluate the use of ultrasonographically guided high-intensity focused ultrasound (HIFU) in the salvage of limbs in patients with osteosarcoma. Seven patients underwent HIFU ablation. Laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No severe complications were observed, and preexisting severe pain disappeared in patients treated with HIFU. Alkaline phosphatase did not show statistically significant changes before and after HIFU treatment, although Alkaline phosphatase did change 1 mo and 2 mo after HIFU. Complete response of the tumor was achieved in three patients with osteosarcoma. Partial response was achieved in another three patients treated with HIFU. Pulmonary metastasis was noted in only one patient 5 mo after HIFU. The median survival time was 68 mo. All patients were alive 3 y after HIFU treatment. Five patients were alive at follow-up visits after 5 y. One patient died from cachexia and infection after 4 y, another patient died of cardiac arrest attack after 4 y. Three patients died of lung dysfunction from pulmonary metastases after 5 y. The five-year survival rate was 71.4%. The authors concluded that HIFU ablation was a safe and feasible method of treatment of osteosarcoma which salvages the limb, but large-scale randomized clinical trials are necessary for confirmation.
Cancer biology & therapy 07/2009; 8(12):1102-8. · 2.64 Impact Factor
