Overexpression of ABCG2 confers resistance to pevonedistat, an NAE inhibitor.

Pevonedistat is a potent, selective, first-in-class NEDD8 activating enzyme inhibitor. It is now under multiple clinical trials that investigate its anticancer effect against solid tumors and leukemia. ATP-binding cassette (ABC) transporters are membrane proteins that are involved in mediating multidrug resistance (MDR). In this article, we reveal that pevonedistat is a substrate of ABCG2 which decreases the therapeutic effect of pevonedistat. The cytotoxicity of pevonedistat was significantly weakened in ABCG2-overexpressing cells, and the drug resistance can be reversed by ABCG2 inhibitors. The ATPase assay suggested that pevonedistat can stimulate ABCG2 ATPase activity in a concentration-dependent manner. Pevonedistat showed little effect on the expression level or subcellular localization of ABCG2 after 72 h treatment. Furthermore, a pevonedistat resistance cell line S1-PR was established and overexpressed ABCG2. Generally, our study provides evidence that ABCG2 can be a prominent factor leading to pevonedistat-resistance. Furthermore, ABCG2 may also be utilized as a biomarker to monitor the development of pevonedistat resistance during cancer treatment.

Computer-aided rigid choledochoscopy lithotripsy for hepatolithiasis.

BACKGROUND: Hepatolithiasis is challenging for surgeons to treat especially in patients with previous hepatobiliary surgery. The aim of the study was to report our experience of rigid choledochoscopy lithotripsy in targeted treatment of hepatolithiasis under the guidance of a medical image three-dimensional visualization system, which we developed and patented (software copyright no: 2008SR18 798) by comparing it with hepatectomy without a three-dimensional (3D) reconstruction technique. METHODS: Between December 2007 and March 2013, 64 patients underwent rigid choledochoscopy lithotripsy based on 3D visualization technology conducted by a medical image three-dimensional visualization system for hepatolithiasis (group A). During the same period, 61 patients with hepatolithiasis were selected for hepatectomy (group B). Comparative analysis was made of demographic and perioperative characteristics of the two groups. RESULTS: 3D visualization was instructive for surgeons on how the stones were distributed and what the spatial relationship was between stones and the intrahepatic vascular system. Compared with patients in group B, those in group A had a significantly lower intermediate residual stone rate, a faster operating time, a lower intraoperative blood loss and intraoperative blood transfusion, a shorter postoperative hospital stay, less postoperative complications, and more liver function reserved (P < 0.05 for all). Final residual stone rate, stone recurrence rate, and recurrent cholangitis rate were similar. CONCLUSIONS: 3D visualization technology provides an important reference and a valuable planning for rigid choledochoscopy lithotripsy, which is a feasible and effective method for management of hepatolithiasis.

A comparative study of the diagnostic accuracy of the medical image three-dimensional visualization system, MRCP, CT and US in hepatolithiasis.

BACKGROUND/AIMS: The aim of this study was to compare the results of the Three-Dimensional Visualization System (MI-3DVS or 3D) in the diagnostic accuracy of hepatolithiasis. METHODOLOGY: From February 2007 to March 2013, forty-eight patients with hepatolithiasis were admitted to our department. Meanwhile, choosing forty-one patients without hepatolithiasis as controlgroup. MI-3DVS, MRCP, CT, and US were performed and the results of these imaging methods in detecting calculi distribution, bile duct dilatation/stricture, and liver atrophy/hypertrophy were analyzed. RESULTS: The total display accuracy on bile duct stricture/dilatation using by 3D was higher than using by MRCP, CT, US. The total accuracy of 3D in detecting the liver atrophy was 96.6%, which was superior to that of US (p=0.009) and CT (p=0.044), and there was no significant difference compared with MRCP (P=0.120). The results on diagnosis of calculi distribution by 3D was better than US (p=0.003) and MRCP (p=0.029), but had no significantly difference compared with CT (P=0.246), and they were all close to intraoperative findings. CONCLUSIONS: MI-3DVS could be used to select patients with hepatolithiasis as a supplement approach to other imaging methods and as an innovative means in pre-operative assessment and post-operative follow-ups in hepatolithiasis.

Management complicated hepatolithiasis with operative rigid choledochoscope guided by computed tomography (CT)-based 3D reconstruction technique.

BACKGROUND: Treatment of complicated hepatolithiasis is complex and difficult. In this report, we present a novel approach to manage complicated hepatolithiasis using the rigid choledochoscope guided by CT-based 3D reconstruction technique with or without hepatectomy. METHODS: Between February 2012 to December 2013, 25 patients with complicated hepatolithiasis underwent rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy. 27 patients with complicated hepatolithiasis underwent a traditional operation (traditional method group) from June 2011 to January 2012. All operations were performed by the authors. RESULTS: The final stone clearance rate of the rigid choledochoscope group was 96%, whereas that of the traditional method group was 74.1% (P=0.032). There was no patient died of postoperative mortality in two groups. Moreover, the operative time in the traditional method group was significantly longer than that in the rigid choledochoscope group (P=0.010). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSIONS: Operative rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy may be an effective and safe treatment for complicated hepatolithiasis.

3D Reconstruction Aids Surgery For Complicated Hepatolithiasis.

BACKGROUND/AIMS: Three-dimensional (3D) imaging may improve surgical interventions for complicated hepatolithiasis. METHODOLOGY: Between July 2008 and December 2012 a total of 131 patients with complicated hepatolithiasis underwent surgical therapy in the Department of Hepatobiliary Surgery Zhujiang Hospital, Southern Medical University. 77 patients received preoperative planning using a computed tomography (CT)-based 3D reconstruction technique, and 54 received treatment based on preoperative planning with traditional imaging (CT, ultrasonography, magnetic resonance imaging/magnetic resonance cholangiography). Perioperative and long-term outcomes were analyzed. RESULTS: 3D reconstruction facilitated significantly more accurate diagnosis of pathological morphology than conventional imaging methods, as confirmed during surgery. Patients that received 3D reconstruction preoperative planning had significantly better clinical outcomes. The immediate stone clearance rates were 92.2% and 61.1%, respectively. Additional postoperative choledochoscopic lithotripsy raised the clearance rates to 94.8% and 81.5%, respectively. The hospital mortality rates were 0% and 1.9%, respectively, and the complication rates were 33.8% and 44.4%, respectively. With a median follow-up of 28 months (5-38 months), the long-term overall asymptomatic survival rates were 80.5% and 46.3%, respectively. 3D reconstruction preoperative planning was a significant prognostic protective factor of long-term asymptomatic survival for the patients with complicated hepatolithiasis (Cox regression analysis, RR = 0.348, 95% confidence interval 0.185-0.657, p = 0.001). CONCLUSION: Surgical therapy conducted following preoperative planning using 3D reconstruction achieved better clinical outcomes than conventional imaging techniques. Whilst conventional imaging techniques accurately identify intrahepatic stones, they are less capable of identifying bile duct stricture.

Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects.

BACKGROUND: The impact of hepatic venous anatomic variations on hepatic resection and transplantation is the least understood aspect of liver surgery. METHODS: A prospective three-dimensional computed tomography study was undertaken on 200 consecutive subjects with normal livers to determine the prevalence of surgically significant hepatic venous anatomic variations. RESULTS: The prevailing pattern of the three hepatic veins in these subjects was a right hepatic vein (RHV) and a common trunk for the middle (MHV) and left (LHV) hepatic veins (122/200, 61%). The remaining patients had the RHV, MHV, and LHV draining independently into the inferior vena cava (IVC). In 39% of patients, the RHV was small and was compensated by a large right inferior hepatic vein (21.0%), an accessory RHV (8.5%) or a well-developed MHV (6.5%). A segment 4 vein was seen in 51.5% of patients. This segment 4 vein joined the LHV (26%), the MHV (17.5%), or the IVC (8%). An umbilical vein and a segment 4 vein were seen in 3.5% of patients. These two veins joined either the LHV (2.0%) or the MHV (1.5%). CONCLUSIONS: Knowing the variations of hepatic veins before surgery is useful during both partial hepatectomy and donor operations for living related liver transplantation.

Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression.

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.

Decreasing hyaluronic acid combined with drug-loaded nanoprobes improve the delivery and efficacy of chemotherapeutic drugs for pancreatic cancer.

Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

Gold nanoparticles: synthesis, physiochemical properties and therapeutic applications in cancer.

Gold nanoparticles (AuNPs) have been shown to be useful as carriers of various anticancer drugs as well as diagnosis platforms. In this review, we discuss the synthesis and physiochemical properties of AuNPs. We also highlight the photothermal and photodynamic properties of AuNPs and relevant applications in therapeutic studies. Furthermore, we review the applications of AuNPs in cancer treatment as and their underlying anticancer mechanisms in multiple types of cancer.

Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model.

Cabozantinib (CBZ) is a small molecule tyrosine kinase receptor inhibitor, which could also inhibit the ABCG2 transporter function. Therefore, CBZ could re-sensitize cancer cells that are resistant to ABCG2 substrate drugs including topotecan (TPT). However, its reversal effect against TPT resistance has not been tested in a TPT-induced resistant cancer model. In this study, a new TPT selected human non-small cell lung cancer (NSCLC)-resistant cell model NCI-H460/TPT10 with ABCG2 overexpression and its parental NCI-H460 cells were utilized to investigate the role of CBZ in drug resistance. The in vitro study showed that CBZ, at a non-toxic concentration, could re-sensitize NCI-H460/TPT10 cells to TPT by restoring intracellular TPT accumulation via inhibiting ABCG2 function. In addition, the increased cytotoxicity by co-administration of CBZ and TPT may be contributed by the synergistic effect on downregulating ABCG2 expression in NCI-H460/TPT10 cells. To further verify the applicability of the NCI-H460/TPT10 cell line to test multidrug resistance (MDR) reversal agents in vivo and to evaluate the in vivo efficacy of CBZ on reversing TPT resistance, a tumor xenograft mouse model was established by implanting NCI-H460 and NCI-H460/TPT10 into nude mice. The NCI-H460/TPT10 xenograft tumors treated with the combination of TPT and CBZ dramatically reduced in size compared to tumors treated with TPT or CBZ alone. The TPT-resistant phenotype of NCI-H460/TPT10 cell line and the reversal capability of CBZ in NCI-H460/TPT10 cells could be extended from in vitro cell model to in vivo xenograft model. Collectively, CBZ is considered to be a potential approach in overcoming ABCG2-mediated MDR in NSCLC. The established NCI-H460/TPT10 xenograft model could be a sound clinically relevant resource for future drug screening to eradicate ABCG2-mediated MDR in NSCLC.

VKNG-1 Antagonizes ABCG2-Mediated Multidrug Resistance via p-AKT and Bcl-2 Pathway in Colon Cancer: In Vitro and In Vivo Study.

The emergence of multidrug resistance (MDR) to chemotherapeutic drugs is a major problem in the therapy of cancer. Knowledge of the mechanisms of drug resistance in cancer is necessary for developing efficacious therapies. ATP-binding cassette (ABC) transporters are transmembrane proteins that efflux chemotherapeutic drugs from cancer cells, thereby producing MDR. Our research efforts have led to the discovery of VKNG-1, a compound that selectively inhibits the ABCG2 transporter and reverses resistanctabe to standard anticancer drugs both in vitro and in vivo. VKNG-1, at 6 µM, selectively inhibited ABCG2 transporter and sensitized ABCG2-overexpressing drug-resistant cancer cells to the ABCG2 substrate anticancer drugs mitoxantrone, SN-38, and doxorubicin in ABCG2-overexpressing colon cancers. VKNG- 1 reverses ABCG2-mediated MDR by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the mRNA and protein levels. Moreover, VKNG-1 inhibits the level of phosphorylated protein kinase B (PKB/p-AKT), and B-cell lymphoma-2 (Bcl-2) protein which may overcome resistance to anticancer drugs. However, the in vitro translocation of ABCG2 protein did not occur in the presence of 6 µM of VKNG-1. In addition, VKNG-1 enhanced the anticancer efficacy of irinotecan in ABCG2- overexpressing mouse tumor xenografts. Overall, our results suggest that VKNG-1 may, in combination with certain anticancer drugs, represent a treatment to overcome ABCG2-mediated MDR colon cancers.

Application of a medical image processing system in liver transplantation.

BACKGROUND: At present, imaging is used not only to show the form of images, but also to make three-dimensional (3D) reconstructions and visual simulations based on original data to guide clinical surgery. This study aimed to assess the use of a medical image-processing system in liver transplantation surgery. METHODS: The data of abdominal 64-slice spiral CT scan were collected from 200 healthy volunteers and 37 liver cancer patients in terms of hepatic arterial phase, portal phase, and hepatic venous phase. A 3D model of abdominal blood vessels including the abdominal aorta system, portal vein system, and inferior vena cava system was reconstructed by an abdominal image processing system to identify vascular variations. Then, a 3D model of the liver was reconstructed in terms of hepatic segmentation and liver volume was calculated. The FreeForm modeling system with a PHANTOM force feedback device was used to simulate the real liver transplantation environment, in which the total process of liver transplantation was completed. RESULTS: The reconstructed model of the abdominal blood vessels and the liver was clearly demonstrated to be three-dimensionally consistent with the anatomy of the liver, in which the variations of abdominal blood vessels were identified and liver segmentation was performed digitally. In the model, liver transplantation was simulated subsequently, and different modus operandi were selected successfully. CONCLUSION: The digitized medical image processing system may be valuable for liver transplantation.

[Application of the medical image three-dimensional visualization system of abdomen in diagnosis and evaluating resectability of pancreatic tumors].

OBJECTIVE: To study the value and the clinical application of the Medical Image three-dimensional Visualization System of Abdomen (MI-3DVS) in diagnosis and evaluating resectability of pancreatic tumor. METHODS: Twelve patients with pancreatic tumor were tested with 64-slice helical CT (64-MSCT) angiography, and the CT data was reconstructed with MI-3DVS from November 2008 to August 2009. The 3D findings were adopted in diagnosis and evaluating resectability, and the results were compared with surgical operation and the pathological finding. There were 7 male and 5 female, aged from 14 to 83 years. Within the 12 cases, there were 4 cases with pancreatic carcinoma, 5 cases with pancreatic solid pseudopapillary tumor, 2 cases with pancreatic serous cystadenoma, 1 case with pancreatic cyst (ductal epithelial papillary hyperplasia). RESULTS: Nine tumors which had been regarded as removable pre-operatively with MI-3DVS were removed successfully. Three patients who were considered unresectable by other hospitals with CT were operated successfully with MI-3DVS. The other 3 patients' tumors were actually not able to be removed as pre-operative evaluation. CONCLUSION: MI-3DVS plays an important role in diagnosis and assessment of resectability of pancreatic tumor.

Methyl-Cantharidimide (MCA) Has Anticancer Efficacy in ABCB1- and ABCG2-Overexpressing and Cisplatin Resistant Cancer Cells.

In this study, we investigated the efficacy of methyl-cantharidimide (MCA), a cantharidin (CTD) analog, as an anticancer drug, in cancer cells overexpressing either ABCB1 or ABCG2 transporters and in cisplatin-resistant cancer cells. The results indicated that: (i) MCA was efficacious in the ABCB1-overexpressing cell line, KB-C2, and the ABCB1-gene-transfected cell line, HEK293/ABCB1 (IC50 from 6.37 to 8.44 mM); (ii) MCA was also efficacious in the ABCG2-overexpressing cell line, NCI-H460/MX20, and the ABCG2-gene-transfected cell lines, HEK293/ABCG2-482-R2, HEK293/ABCG2-482-G2, and the HEK293/ABCG2-482-T7 cell lines (IC50 from 6.37 to 9.70 mM); (iii) MCA was efficacious in the cisplatin resistant cancer cell lines, KCP-4 and BEL-7404/CP20 (IC50 values from 7.05 to 8.16 mM); (iv) MCA (up to 16 mM) induced apoptosis in both BEL-7404 and BEL-7404/CP20 cancer cells; (v) MCA arrested both BEL-7404 and BEL-7404/CP20 cancer cells in the G0/G1 phase of the cell cycle; (vi) MCA (8 mM) upregulated the expression level of the protein, unc-5 netrin receptor B (UNC5B) in HepG2 and BEL-7404 cancer cells. Overall, our results indicated that MCA's efficacy in ABCB1- and ABCG2-overexpressing and cisplatin resistant cancer cells is due to the induction of apoptosis and cell cycle arrest in the G0/G1 phase.

Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor.

Overexpression of ABCG2 remains a major impediment to successful cancer treatment, because ABCG2 functions as an efflux pump of chemotherapeutic agents and causes clinical multidrug resistance (MDR). Therefore, it is important to uncover effective modulators to circumvent ABCG2-mediated MDR in cancers. In this study, we reported that AZ-628, a RAF kinase inhibitor, effectively antagonizes ABCG2-mediated MDR in vitro. Our results showed that AZ-628 completely reversed ABCG2-mediated MDR at a non-toxic concentration (3 µM) without affecting ABCB1-, ABCC1-, or ABCC10 mediated MDR. Further studies revealed that the reversal mechanism was by attenuating ABCG2-mediated efflux and increasing intracellular accumulation of ABCG2 substrate drugs. Moreover, AZ-628 stimulated ABCG2-associated ATPase activity in a concentration-dependent manner. Docking and molecular dynamics simulation analysis showed that AZ-628 binds to the same site as ABCG2 substrate drugs with higher score. Taken together, our studies indicate that AZ-628 could be used in combination chemotherapy against ABCG2-mediated MDR in cancers.

Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line.

While topotecan (TPT) is a first- and second-line chemotherapeutic drug in treating lung cancer, the development of drug resistance in tumors still reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of topotecan resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in topotecan-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143. The NCI-H460/TPT10 cell line and its parental cell line can be useful for drug screening and developing targeted strategies to overcome ABCG2-mediated MDR in NSCLC.

Lipid-Saporin Nanoparticles for the Intracellular Delivery of Cytotoxic Protein to Overcome ABC Transporter-Mediated Multidrug Resistance In Vitro and In Vivo.

Although the judicious use of anticancer drugs that target one or more receptor tyrosine kinases constitutes an effective strategy to attenuate tumor growth, drug resistance is commonly encountered in cancer patients. The ATP-binding cassette transporters are one of the major contributors to the development of multidrug resistance as their overexpression significantly decreases the intracellular concentration and thus, the efficacy of certain anticancer drugs. Therefore, the development of treatment strategies that would not be susceptible to efflux or excretion by specific ABC transporters could overcome resistance to treatment. Here, we investigated the anticancer efficacy of saporin, a ribosome-inactivating protein. Since saporin has poor permeability across the cell membrane, it was encapsulated in a lipid-based nanoparticle system (EC16-1) that effectively delivered the formulation (EC16-1/saporin) intracellularly and produced anti-cancer efficacy. EC16-1/saporin, at nanomolar concentrations, significantly inhibited the cellular proliferation of parental and ABCB1- and ABCG2-overexpressing cancer cells. EC16-1/saporin did not significantly alter the subcellular localization of ABCB1 and ABCG2. In addition, EC16-1/saporin induced apoptosis in parental and ABCB1- and ABCG2-overexpressing cancer cells. In a murine model system, EC16-1/saporin significantly inhibited the tumor growth in mice xenografted with parental and ABCB1- and ABCG2-overexpressing cancer cells. Our findings suggest that the EC16-1/saporin combination could potentially be a novel therapeutic treatment in patients with parental or ABCB1- and ABCG2-positive drug-resistant cancers.

[Minimally invasive surgical treatment with per-pancreat region for sever acute pancreatitis.].

OBJECTIVE: To investigate the clinical effect of the minimally invasive surgical treatment with per-pancreat region for sever acute pancreatitis (SAP). METHODS: Fify-four cases of SAP were divided into two groups, patients of group A (n = 28) were given minimally invasive surgical treatments (step 1: under local anesthesia, patients were put the home-made double cannula in the abdominal around the region of pancreas.step 2:patients with biliary stone were performed by laparoscopical operations). Patients of group B (n = 26) were treatment by open operations including biliary decompression, gastrostomy, jejunostomy, removing necrotic pancreatic organizations and puting the double cannula around the region of pancreas. Through double cannula around the pancreas area, all patient's cavity were persistently douched using 0.5% 5-FU saline solution. RESULTS: Washed after one week, two groups patient's drainage fluid amylase concentration were decreased significantly (t = 2.68, P = 0.013; t = 2.41, P = 0.028), patient's white cell count, body temperature, heart rate of Groups A were also decreased significantly (t = 2.32, P = 0.035; t = 2.39, P = 0.021; t = 2.38, P = 0.023). Compared with group B, the mortality, the incidence of complications, hospitalization time and total cost of treatment of group A patients were significantly lower than that of group B (chi(2) = 8.62, P = 0.001; chi(2) = 6.35, P = 0.014; t = 2.22, P = 0.034; t = 2.67, P = 0.010), but the cure rate was significantly higher than that of group B (chi(2) = 3.89, P = 0.045). CONCLUSIONS: Minimally invasive surgical treatment of per-pancreatic region for SAP can not only remove the causes, but also fully drainage and timely block the pathological vicious cycle of SAP. What is more, it is simple, minimally invasive and have few complications and significant effect.

[Study on the application of value of digital medical technology in the operation on primary liver cancer].

OBJECTIVE: To study the clinical application of digital medical in the operation on primary liver cancer. METHODS: The patients (n=11) with primary hepatic carcinoma treated between February and July 2008, including 9 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma, were scanned using 64 slices helicon computerized tomography (CT) and the datasets was collected. Segment and three-dimensional (3D) reconstruction of the CT image was carried out by the medical image processing system which was developed. And the 3D moulds were imported to the FreeForm Modeling System for smoothing. Then the hepatectomy in treatment of hepatoma and implanting of catheter were simulated with the force-feedback equipment (PHANToM). Finally, 3D models and results of simulation surgery were used for choosing mode of operation and comparing with the findings during the operation. RESULTS: The reconstructed models were true to life, and their spatial disposition and correlation were shown clearly; Blood supply of primary liver cancer could be seen easily. In the simulation surgery system, the process of virtual partial hepatectomy and implanting of catheter using simulation scalpel and catheter on 3D moulds with PHANToM was consistent with the clinical course of surgery. Life-like could be felt and power feeling can be touched during simulation operation. CONCLUSIONS: Digital medical benefited knowing the relationship between primary liver cancer and the intrahepatic pipe. It gave an advantage to complete primary liver cancer resection with more liver volume remained. It can improve the surgical effect and decrease the surgical risk and reduce the complication through demonstrating visualized operation before surgery.

Targeting carbon nanotubes based on IGF-1R for photothermal therapy of orthotopic pancreatic cancer guided by optical imaging.

Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity. Single-walled carbon nanotubes (SWNTs) can remedy the above inadequacies. Herein, we report our water-soluble, bio-stable and low-toxicity SWNTs with excellent photothermal conversion efficiency. Specific modifications can enable visualization of the aggregate characteristics of SWNTs at the macroscopic or microscopic level in tumors. The dye-conjugated SWNTs bound with targeting antibodies that can induce them specifically targeting to pancreatic tumors for purposes of performing dyes imaging-guided cytotoxic PTT. PTT using this method achieves precise and excellent curative effects with minimal adverse effects, thus providing a promising strategy for anticancer therapy.