Search

Purpose:To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC). Materials and methods:Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For bothin vitroconfirmation andin vivovalidation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology. Results:In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29 ± 6% vs. 56 ± 9%, 93 ± 4%, and 100 ± 5%,p < .05). Ultrasound imaging of treated animal xenografts showed smaller relative tumour volume in combination therapy group than those in three control groups (0.74 ± 0.19 vs. 1.79 ± 0.24, 3.14 ± 0.49 and 3.22 ± 0.52,p < .05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumours in the combination therapy group, compared to those in three control groups (1.2 ± 0.1 vs. 1.9 ± 0.2% vs. 3.3 ± 0.6% vs. 3.5 ± 0.4%,p < .05). These imaging findings were correlated well with histologic confirmation. Conclusion:RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the technical feasibility of using ultrasound-guided intratumoral radiofrequency hyperthermia (RFH) to enhance local chemotherapy of rat orthotopic pancreatic cancers., Materials and Methods: Orthotopic pancreatic cancer masses were established by inoculating luciferase/mCherry labeled-pancreatic cancer cells into the pancreatic tails of Lewis model rats via a laparotomy approach. Twenty-four rats with pancreatic cancer and 24 mice with subcutaneous pancreatic cancer xenografts in four study groups (n = 6/group) received various treatments: i) combination therapy of intratumoral MR imaging-heating-guidewire-mediated RFH (42oC) plus local chemotherapy (gemcitabine); ii) intratumoral chemotherapy alone; iii) RFH alone; and (iv)phosphate-buffered saline (PBS). Transcutaneous ultrasound imaging was used to guide the treatment and subsequently follow changes in tumor sizes. Bioluminescence optical imaging was performed to follow photon signal changes. Sonographic and optical findings were correlated with histology at 14 days., Results: Optical imaging demonstrated a significantly decreased bioluminescence signal in mice with combination therapy group, compared with the other control groups (0.51±0.18 VS 1.6±0.4 VS 3.18±0.9 VS 3.5±0.96, p < 0.05). Ultrasound imaging showed the smallest tumor volumes of both mice and rat group with the combination therapy, compared with other control groups (0.62±0.16 VS 1.25±0.19 VS 2.28±0.25 VS 2.64±0.26, p < 0.05) and (0.75±0.18 VS 1.31±0.30 VS 1.61±0.28 VS 1.72±0.28, p < 0.05). Both imaging findings were confirmed by histologic correlation., Conclusion: Intratumoral RFH can augment the chemotherapeutic effect in an orthotopic pancreatic cancer model.

Despite recent advances in surgical technique and treatment strategies for esophageal cancer (EC), to effectively manage the advanced (metastatic or disseminated) and recurrent EC still remain a great challenge. The aim of this study was to determine the feasibility of using intra-esophagus radiofrequency hyperthermia to enhance local HSV-TK/ganciclovir-mediated suicide gene therapy of an innovative animal models with orthotopic esophageal squamous cancers. Human esophageal squamous cancer (ESCa) cells were labeled with lentivirus/luciferase. ESCa cells and nude rats with orthotopic ESCa were divided into in four groups (n = 6/group) and treated with: i) combination therapy of MR imaging-heating-guidewire-mediated radiofrequency hyperthermia ((RFH, 42°C) plus local HSV-TK/GCV; ii) HSV-TK/GCV alone; iii) RFH alone; and (iv) phosphate-buffered saline (PBS). Bioluminescence optical imaging and transcutaneous ultrasound imaging were used to follow up bioluminescence signal and size changes of tumors among different groups over two weeks, which were correlated with subsequent histology. We demonstrated that combination therapy of RFH with gene therapy resulted in the lowest cell proliferation (37.5±8.6%, P<0.0001), rendered the smallest relative tumor volume (0.90±0.15, P<0.01), and relative bioluminescence optical imaging photon signal intensity (0.81±0.17, P<0.01) of orthotopic esophageal cancers, compared with groups treated with gene therapy alone, RFH alone and PBS. Our study indicated that intra-esophageal radiofrequency hyperthermia could enhance the HSV-TK-mediated effect on esophageal squamous cancers.

Objective: To retrospectively explore the status of primary patency after subintimal angioplasty (SIA) and identify the risk factors affecting for primary patency of occlusive lesions in femoral arteries after SIA in patients with diabeticses mellitus., Methods: From January 2009 to May 2011, 43 diabetics patients with 43 occlusive femoral arteries were successfully underwent subintimal angioplasty successfully with or without stenting.Recurrent stenosis was defined as an arterial diameter reduction of over 50%. And arterial occlusion was confirmed by an absence of color or power signal in the arterial lumen measured on color Doppler. The Kaplan-Meier method was employed to determine the primary patency. A multivariate analysis was performed with Cox's proportional hazard regression model to determine the independent factors for effects on primary patency., Results: A total of 17 morphologic abnormalities occurred during a median follow-up period of 21 (14-32) months. The median follow time of the successful 43 patients was 21 months (from 14 to 32 month). Minor complications occurred in 4 patents. There was no early mortality. A total of 17 morphologic abnormalities occurred during follow-up. The cumulative primary patency at 6, 12, 12 and 24 months were (86 ± 5)%, (75% ± 7)% and (43 ± 12)% respectively. Primary patency was affected negatively by the number of occlusive run-off vessels (B = -4.417, SX- = 1.627, P = 0.007) and the severity degree according to the Inter-society consensus for the management of peripheral arterial disease (TASC II) classification (B = -2.502, SX- = 0.955, P = 0.009), and positively by the a history of smoking (B = 3.115, SX- = 1.523, P = 0.041)., Conclusions: Subintimal angioplasty is a less invasive procedure with a lower rate of morbidity and adequate cceptable patency. And the number of occlusive run-off vessels, lesion typing degree of severity according to the TASC II classification negatively and smoking positively have significant influence effects on the primary patency in diabetics patients.

Background: The importance of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population., Methods: Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms (SNPs) (rs1801131, rs1801133, rs2274976) genotypes of the MTHFR gene were determined by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)., Results: The average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G (χ(2) = 22.7, P < 0.01) and rs1801131A/A (χ(2) = 14.3, P = 0.008) were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes (G/A and A/A) and of the rs1801131C allele genotypes (A/C and C/C) were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups (χ(2) = 20.69, P = 0.000 124)., Conclusions: These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.