阿霉素肝动脉热化疗治疗兔肝VX2移植癌

背景与目的:研究表明,加热可提高兔VX2细胞对阿霉素(adriamycin,ADM)的增敏作用,可促进ADM进入细胞内,从而提高ADM的抗癌作用。作者在兔VX2细胞行ADM热化疗研究和兔肝VX2细胞移植瘤模型建立基础上,进行ADM兔肝动脉热灌注,以评价介入性化疗与介入性热化疗对兔肝癌的抑瘤效果。方法:将VX2细胞接种于60只新西兰白兔肝右叶,建立兔肝VX2移植癌模型。随机分4组,每组15只。利用导管经肝动脉分别给各组37℃生理盐水(第1组)、37℃ADM溶液(第2组)、60℃生理盐水(第3组)、60℃ADM溶液(第4组),1周后观察各组肿瘤体积及血清AST水平,观察荷瘤兔的存活期。结果:第4组肿瘤生长率(0.53±0.21)%,与第1组(3.48±1.17)%相比有显著性差异(P<0.01),与第2组的(1.09±0.26)%、第3组的(3.32±1.28)%相比亦有显著性差异(P<0.05)。第4组存活期(87.0±2.0)天,与第1组(40.5±3.0)天相比差异有显著性(P<0.05)。第4组血清AST水平给药前后变化与其它各组相比无显著性差异(P>0.05),与对第1组相比有显著性差异(P<0.05)。结论:60℃ADM溶液热灌注可降低肿瘤生长率,延长存活期,而对肝功能的损害是可逆的。     

Antitumor and antivascular effects of AC-7700, a combretastatin A-4 derivative,against rat liver cancer

Background. Unlike the many chemotherapeutic agents that do not effectively stop blood flow or induce necrosis in hepatocellular carcinoma, AC-7700 has been shown to inhibit tubulin polymerization and selectively stop tumor blood flow. The aim of this study was to elucidate the antivascular and antitumor effects of AC-7700 on rat hepatoma. Methods. AH-130 cells, a rat hepatoma cell line, were solidified and implanted into the liver of Donryu rats. Vascularity of the liver tumor was directly identified by in-vivo fluorescence microscopy from 0 to 60 min after the injection of 10 mg/kg AC-7700. To observe the antivascular effect of AC-7700, the vascular density of the tumor was measured and assessed as the ratio of preinjection to postinjection values. The antitumor effects were evaluated with histopathologic findings and analysis of animal survival. Results. In-vivo microscopic observation showed that tumor perfusion diminished within 30 min after AC-7700 administration. Vascular density in the AC-7700 group was significantly less than that in the control group at 60 min (AC-7700, 26.3 ± 16.4%; control, 88.5 ± 9.2%; P < 0.001). After AC-7700 injection, marked necrosis of tumor cells was observed histologically, and tumor area was decreased significantly (AC-7700, 11.5 ± 15.4 mm²; control, 43.5 ± 18.3 mm²; P < 0.05). The survival rate (50%) of the AC-7700 group animals was better than that of the control group (0%; P < 0.01). Conclusion. Markedly decreased tumor perfusion was induced by AC-7700 within 30 min, and this decrease may have contributed to the tumor necrosis and favorable outcome in the treatment group. AC-7700 appears to be a promising agent for the treatment of hepatocellular carcinoma. Received: September 14, 2001 / Accepted: February 21, 2002     

Investigation of QOL after Laryngectomy Using the UW-QOL Questionnaire with Chinese Patients

OBJECTIVE To assess the postoperative QOL(Quality of Life) of Chinese laryngeal cancer patients who have undergone a partial or total laryngec-tomy, and to analyze their prognostic factors, as well as to assess the feasibility of using the University of Washington Quality of Life (UW-QOL) questionnaire in QOL studies of laryngeal cancer patients, METHODS Using the UW-QOL questionnaire, a survey was conducted in patients treated by a partial or total laryngectomy for laryngeal cancer. RESULTS Questionnaires were sent to 142 patients who were disease-free for more than half a year after surgery. Replies were received from 130 patients (91% response rate) with 118 patients completing the questionnaire. These patients were divided into 2 groups: a partial-laryngectomy group (n=81; excluding cordectomy) and a total -laryngectomy group (n=37). The composite QOL scores of the partial-laryngectomy group (692.3±127.9) were higher than those of total-laryngectomy group (636.4±140.0), showing a statistically significant difference (P<0.05). The partial-laryngectomy group (74.3±23.8; 80.9±20.3) was better than the total-laryngectomy group (40.3±25.8; 69.6±27.1) in speech and appearance (P<0.001; P<0.05); but the total-laryngectomy group (92.6±13.0) was superior to the partial-laryngectomy group (83.0±20.5) in pain (P< 0.01). Six factors including cancer stage, operative modality, complications, postoperative radiotherapy or chemotherapy, living partners and chronic disease before or after operation were related to postlaryngecto-my QOL. CONCLUSION Partial laryngectomy is superior to total laryngectomy in speech, appearance and overall QOL. Besides operative modality, cancer stage, complications, postoperative radiotherapy or chemotherapy, living partners and chronic diseases before or after operation are factors influencing postlaryngectomy QOL. As a whole, the UW-QOL questionnaire is a good instrument for studying QOL of laryngeal cancer patients in China, and it can be used to explore the QOL outcomes obtained from different reconstructive techniques.     

A Molecular Adsorbent Recycling System in Treating Posthepatectomy Acute Hepatic Failure Patients with Hepatocellular Carcinoma： a Bridge to Liver Transplantation

OBJECTIVE To evaluate the effect and safety of a Molecular Adsorbent Recycling System (MARS) in treating posthepatoectomy hepatic failure (AHF) patients surgically treated for primary hepatocellular carcinoma (HCC). METHODS 12 AHF patients induced by resection of HCC were treated with MARS before orthotopic liver transplantation (OLT). Their vital signs, urine volume, APACHEⅢand Glasgow scores were monitored. Routine laboratory blood tests, measurements of coagulatory function, liver and kidney function, serum ammonia, lactic acid and blood gas were conducted before and after treatment with MARS. All of the patients were followed up for a period of 6 months after OLT for prognosis and complication assessment. RESULTS Each patient was treated with MARS for 2-5 times (average of 3.6) with a length of 8-24 h each time. Their mean arterial blood pressure and urine volume were improved, APACHEⅢand Glasgow scores were better. Liver function was improved with the following alterations before and after treatment with MARS: serum ammonia (127.1±21.4 umol/L vs. 77.4±19.7 umol/L, P<0.05), lactic acid (6.53±0.45 mmol/L vs. 3.75±0.40 mmol/L, P<0.05) and total bilirubin (452.3±153.7 umol/L vs. 230.9±115.2 umol/L, P<0.05). However, there was no significant change in platelet count (44.25±3.60×109/L vs. 43.19±8.26×109/L, P>0.05) on international normalized ratio (INR) (2.74±0.50 us. 2.82±0.60, P>0.05), which showed the safety of MARS. For all patients no serious adverse effects occurred during the treatment with MARS. CONCLUSION MARS is effective and safe for treatment of AHF patients with HCC, especially as a bridge to OLT when a donor organ is not available.     

Doxorubicin hydrochloric increases tumour coagulation and end-point survival in percutaneous microwave ablation of tumours in a VX2 rabbit tumour model

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually.

Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5?min and 40 W for 5?min), intravenous injection of 4?mg/kg DOX, and combined therapy. Tumours were analysed at 4?h and 24?h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24?h after treatment.

Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52?cm² ± 0.48 (SD), 4.08?cm² ± 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52?cm² ± 0.48 (SD), 1.69?cm² ± 0.34?cm², respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4?h and 24?h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4?h and 24?h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p < 0.01) or the DOX group (mean 35.17 days ± 7.63, p < 0.01).

Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.     

Microwave ablation of the liver abutting the stomach: Insulating effect of a chitosan-based thermosensitive hydrogel

Purpose: Collateral thermal injury can occur as a serious complication of microwave ablation. This study aimed to assess the insulating effect of a thermosensitive, chitosan-based hydrogel during the percutaneous microwave ablation of liver tissue abutting the stomach. Materials and methods: Thermometry needles (R1–R4) were positioned at 5-mm intervals from a thermal source to measure in vitro the temperature differences due to the hydrogel (R1 closest to the thermal source). Subsequently, two groups of eight rabbits each were injected with 10?mL of hydrogel solution or 410?±?95?mL of 5% saline between the liver and stomach wall. A control group of eight rabbits received no ablation protection measures. The livers were ablated with 40?W for 300?s in 24 ablation zones. The severity of thermal injury to the stomach wall was assessed histologically. Results: In vitro, the mean maximum temperature difference between the R1 and R2 thermometry needles was 31.3°?±?0.1?°C. When R1 was over 60?°C, the mean temperatures at R2, R3, and R4 were 29.8°?±?0.1?°C, 18.6?±?0.3?°C, and 18.1°?±?0.1?°C, respectively. After ablation for 300?s, the maximum temperature at R2 was 48.7°?±?0.2?°C. None of the rabbits injected with gel showed any injury after ablation; however, the other two groups showed varying degrees of thermal injury. Conclusion: The in situ gel protected the adjacent stomach wall from injury during percutaneous microwave ablation of liver tissue. Although the present technique appears promising, further studies are necessary prior to clinical application.     

Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia

Heat-induced hepatotoxicity accompanying hyperthermic liver perfusion was studied in the isolated, haemoglobin-free perfused rat liver. Trypan blue uptake, a sensitive indicator of cell death, was used to examine the relationship between the efflux of oxidized glutathione (oxidative stress), the appearance of cytosolic enzymes in the perfusate and cell death. Livers were perfused at 37, 42, 42.5 and 43°C. The efflux of total glutathione (GSH) and oxidized glutathione (GSSG) increased with time and temperature. Differences between temperature groups were significant for both parameters for 37 versus 42, 42.5 and 43°C (p < 0.05). Temperature-related differences in GSH levels appeared at 15 min for 37 versus 42 °C and in GSSG levels at 30 min for 37 versus 42 and 42.5°C. Biliary excretion of total GSH increased from 72 nmol at 37°C to 144 nmol at 42°C, 160 nmol at 42.5°C and 124 nmol at 43°C, which was significant for 37 versus 42 and 42.5°C (p < 0.05). The release of allantoin into the perfusate, a measure of purine catabolism and flux through xanthine oxidase, was increased at 42, 42.5 and 43°C compared to 37°C (p < 0.05). Liver injury was assessed by measuring the release of asportate aminotransferase (AST) and lactate dehydrogenase (LDH) and uptake of trypan blue after perfusion at each temperature. There was a pronounced release of LDH and AST into the perfusate after 60 min of perfusion at 42, 42.5 and 43°C, the levels of which were significantly different from the 37°C mean level. There was no uptake of trypan blue after 60 min perfusion at 37°C. Perfusion at 42, 42.5 and 43°C resulted in the uptake of trypan blue in the pericentral areas, but the dye uptake was significant (p < 0.05) compared to 37°C at 42.5 and 43°C only. These data show that heat-induced pericentral cell death is minimal after 60 min at 42–43°C, and that the biochemical processes which occurred during this period suggest ‘oxidative stress’ as a causative factor in hyperthermic hepatotoxicity. In addition, this liver toxicity is probably related to xanthine oxidase activity or the depletion of GSH as the initiating event which leads to lipid peroxidation and cellular damage.     

Effect of fat volume on postoperative complications and survival rate after D2 dissection for gastric cancer

Background. D2 lymph node dissection in gastric cancer is controversial in Western countries because of the relatively high complication and mortality rates. The purpose of this study was to clarify the effects of fat volume on operation factors, postoperative complications, and survival in gastric cancer surgery. Methods. We studied 293 consecutive patients who had undergone distal gastrectomy with D2 dissection for gastric cancer at our hospital between 1990 and 1997. The patients were classified into three groups according to their body mass index (BMI; kg/m²). We analyzed differences in the operation time, the amount of blood loss, the postoperative complications and the survival rate among the three groups. Results. Group A patients had a BMI of less than 20 (n = 61), group B had a BMI of 20–25 (n = 178), and group C had a BMI of more than 25 (n = 54). There were significant differences in operation time (group A, 206 ± 66 min; group B, 226 ± 61 min; group C, 252 ± 61 min; P < 0.05), blood loss (group A, 417 ± 282 ml; group B, 501 ± 295 ml; group C, 605 ± 333 ml; P < 0.05), and postoperative complications (group A, 3.3%; group B, 5.6%; group C, 22.0%). There were significant differences in postoperative complications between groups A and C, and between groups B and C. However, the difference between groups A and B was not significant, and no significant difference in survival rate was seen among the three groups. Conclusion. Fat volume definitely increases the postoperative complications. Accordingly, the high rate of postoperative complications of D2 surgery in Western countries may be related to the patients' relative obesity. Received: September 1, 2000 / Accepted: October 23, 2000     

Double-blind,placebo-controlled lithium treatment in chemotherapy induced aplasia for AML: Reduced antibiotic requirement

A double-blind placebo-controlled study on lithium (Li) therapy after chemotherapy-induced bone marrow aplasia was undertaken in 53 patients with acute myeloblastic leukemia (AML). No difference was observed between the two groups for the duration of aplasia, the number of units of platelets or RBC transfused, the complete remission rate or the disease free survival. However, a statistically significant reduction in the number of days of antibiotic therapy required was found in the treated group (10.55 ± 2.72 vs 12.73 ± 3.60,P < 0.05).     

靶向IGFIR的siRNA抑制人肝癌细胞SMMC7721裸鼠移植瘤的实验研究

Objective:To investigate the effect of insulin-like growth factor 1 receptor (IGF1R) small interfering RNA (siRNA)on the growth of human liver cancer SMMC7721 cell xenograft in nude mice.Methods:siRNAtargeting IGF1R was designed,and plasrnid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-1GF1R-siRNAcells); the cells transfected with SMMC7721-1GF1 R-mutation (SMMC7721-1GF1 R-mutation cells) were used as negative control,and untransfected cells as empty control.Stable cell clones were screened by G418,and transplanted into nude mice to establish cancer xenograft.Tumor growth was monitored.Tumor morphology was observed with HE staining.The expression of IGF1R protein in tumor tissues was detected by Western blot.Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry.Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.Results:The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P＜0.05).Necrosis and cell apoptosis were found in SMMC7721-1GF1R-siRNA group.The expression of tGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P＜0.05).MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (11.3±4.4 vs.36.7±7.6 and 28.4±6.5,P＜0.05).The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1 R-mutation and SMMC7721 groups [(50.2±6.4)% vs.(5.4±1.0)% or (6.0±2.1)%,P＜0.05].Conclusion:1GF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.     

Lentivirus-mediated CD/TK fusion gene transfection neural stem cell therapy for C6 glioblastoma

A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat’s neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells’ transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p?<?0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6 %, p?<?0.05) either in vitro or in vivo (35.47 %, p?<?0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76?±?1.37 mm³, which is smaller than the others (group2 27.28?±?4.11 mm³, group3 27.94?±?2.08 and 28.61?±?2.97 mm³; p?<?0.05). The other groups’ tumor size was not significant (p?>?0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p?<?0.05; group 1 48.86?±?1.97, group 2 28.67?±?3.75, group 3 31.5?±?1.27, group 4 29.3?±?1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl–guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.     

Interaction between adriamycin cytotoxicity and hyperthermia: growth-phase-dependent thermal sensitization

Thermal sensitization of adriamycin cytotoxicity was studied in vitro and in vivo using tumour cells originated from a spontaneous mouse fibrosarcoma, FSa-II. The adriamycin dose-cell survival curve for exponentially growing cells was biphasic with the initial sensitive portion followed by a resistant tail. The survival curves determined in vitro as a function of treatment time at various temperatures were also biphasic. With increasing temperatures the initial portion became steeper and the resistant fraction decreased. At a temperature of 43°C, which gives lethal damage to cells by itself, the cell survival decreased rapidly during the initial 30 min of treatment and became relatively constant for subsequent treatment times up to 180 min. The tumour response determined by the median tumour growth time for one-half of treated tumours to reach 1000 mm³ from the treatment day (35 mm³) indicated that the tumour response to adriamycin was independent of temperature. Hyperthermia at 43·5°C for 60 min prolonged the tumour growth time without showing chemosensitization. The maximum drug dose used was 12 mg/kg that is <LD₁₀ or the drug dose that kills animals with < 10% probability. The dose-response curves (tumour growth versus drug dose) showed identical slopes at room temperature, 41·5 and 43·5°C. Further studies were conducted in vitro. Plateau phase cells were treated with graded adriamycin doses for 60 min at 37°C, or with a constant adriamycin dose of 0·25 µg/ml for various times at 37 or 43°C. The dose-cell survival curves for both exponential and plateau phase cells were biphasic, but the plateau phase cells were more resistant to adriamycin at 37°C than the exponential phase cells. The survival curve for plateau phase cells, determined as a function of treatment time, showed an initial shoulder followed by an exponential portion. Compared with the heat survival curve at 43°C, the survival curve for the drug treatment at 43°C was identical to that for the heat alone treatment for the first 60 min and then became steeper than the heat alone survival curve. These results suggest that adriamycin cytotoxicity may be enhanced at elevated temperatures only when tumours are treated for a prolonged time or possibly with a large drug dose.     

Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human Hepatocel-Lular Carcinoma in Nude Mice

Objective To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) in combination of ganciclovir (GCV) against human hepatocellular carcinoma in nude mice. Methods HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups (n=8 each group) Ganciclovir group (Ⅰ), Ad group (Ⅱ), AdCMV-tk/GCV group (under the driving of CMV promoter) (Ⅲ) and AdKDR-tk/GCV group (Ⅳ). Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/(kg·d), ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and Ⅳ (P＜0.05). The mean MVDs in group Ⅰ, Ⅱ, Ⅲand Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 (microvessels/mm2), respectively. Significant differences were found between group Ⅲ and Ⅱ (P＜0.05), Ⅳ and Ⅱ (P＜0.01), and Ⅳ and Ⅲ (P＜0.01). Conclusion Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC.     

Radiofrequency ablation (RFA)-induced systemic tumor growth can be reduced by suppression of resultant heat shock proteins

Purpose: To determine the role of hepatic radiofrequency ablation (RFA) heating parameters and their activation of heat shock proteins (HSPs) in modulating distant tumor growth.

Methods and materials: First, to study the effects of RFA dose on distant tumor growth, rats with subcutaneous R3230 adenocarcinoma (10?±?1?mm) were assigned to 3 different hepatic RF doses (60?°C?×?10?min, 70?°C?×?5?min or 90?°C?×?2?min) that induced identical sized ablation or sham (n?=?6/arm). Post-RFA tumor growth rates, cellular proliferation (Ki-67) and microvascular density (MVD) were compared at 7d. Next, the effect of low and high power doses on local HSP70 expression and cellular infiltration (α-SMA +?myofibroblasts and CD68?+?macrophages), cytokine (IL-6) and growth factor (HGF and VEGF) expression was assessed. Finally, 60?°C?×?10?min and 90?°C?×?2?min RFA were combined with anti-HSP micellar quercetin (MicQ, 2?mg/ml). A total of 150 animals were used.

Results: Lower RF heating (70?°C?×?5?min and 60?°C?×?10?min) resulted in larger distant tumors at 7d (19.2?±?0.8?mm for both) while higher RF heating (90?°C?×?2) led to less distant tumor growth (16.7?±?1.5?mm, p?p?p?p?p?p?p?Conclusion: Hepatic RF heating parameters alter periablational HSP70, which can influence and stimulate distant tumor growth. Modulation of RF heating parameters alone or in combination with adjuvant HSP inhibition can reduce unwanted, off-target systemic tumorigenic effects.     

The efficacy and hyperthermic release of doxorubicin from liposomal doxorubicin hydrochloride in rabbit VX2 tumours

Abstract

Purpose: To establish optimum conditions for anti-tumour therapy, we evaluated the efficacy of doxorubicin using liposomal doxorubicin and local hyperthermia to improve the anti-tumour efficacy over liposomal doxorubicin alone in rabbit VX2 tumours. Materials and methods: A VX2 tumour model was established in New Zealand white rabbits, which were randomly divided into five groups: 1) control, 2) free doxorubicin hydrochloride (Dox), 3) liposomal doxorubicin hydrochloride (L-Dox), 4) L-Dox plus 41?°C thermotherapy (L-Dox?+?41?°C TT); and 5) L-Dox plus 43?°C thermotherapy (L-Dox?+?43?°C TT). To achieve complete tumour remission, multiple high-dose administrations (5?mg/kg, once per week for a total of 3 weeks) were given. An ultrasound hyperthermia instrument was used to induce local hyperthermia and the systemic toxicity of Dox was evaluated by changes in weight, blood count and serum lactic dehydrogenase. The anti-tumour effect of Dox was evaluated by observing the gross tumour volume, weight and rabbit survival. Results: The white blood cell count following administration of Dox or L-Dox was lower than for control animals and those treated with L-Dox?+?41?°C TT. There was no difference between the groups with regard to the red blood cell count. Compared with the control and Dox groups, tumour proliferation was significantly inhibited following administration of L-Dox, L-Dox?+?41?°C TT and L-Dox?+?43?°C TT, as evidenced by the difference in tumour volume, weight and survival time. Differences in tumour proliferation were also found between the L-Dox and thermotherapy groups. Conclusion: Local hyperthermia combined with L-Dox can significantly improve anti-tumour efficacy and reduce systemic toxicity.     

A prognostic fingerprint in liver transplantation for hepatocellular carcinoma based on plasma metabolomics profiling

IntroductionTumor recurrence is a major cause of post-transplant mortality in liver transplantation for hepatocellular carcinoma (HCC). This study aimed to explore an effective noninvasive approach to accurately predict post-transplant tumor recurrence.Materials and methodsMetabolomics profiling was performed on pre-operative plasma from 122 HCC patients undergoing liver transplantation, 52 healthy controls (HC) and 25 liver cirrhosis (LC) patients.ResultsFive prognostic metabolites were identified by univariate analysis (P < 0.01), including phosphatidylcholine (PC) (16:0/P-18:1), PC(18:2/OH-16:0), PC(o-16:0/20:4), nutriacholic acid and 2-oxo-4-methylthiobutanoic acid. In the HCC group, PC(o-16:0/20:4), nutriacholic acid and 2-oxo-4-methylthiobutanoic acid were decreased, while PC(18:2/OH-16:0) was elevated compared with the LC group (e < 0.05). PC(16:0/P-18:1) was associated with tumor size, vascular invasion, and neutrophil-lymphocyte ratio (NLR; P < 0.05). Moreover, PC(18:2/OH-16:0) was also related to tumor number and NLR (P < 0.05). Multivariate cox regression showed that PC(16:0/P-18:1), PC(18:2/OH-16:0), nutriacholic acid and alpha-fetoprotein (AFP) were independent risk factors for tumor recurrence (P < 0.01). A prognostic fingerprint was established as a nomogram, which divided the patients into low risk (n = 45), moderate risk (n = 48) and highrisk groups (n = 29) with discriminated prognosis (P < 0.001). In patients fulfilling the Hangzhou criteria, the fingerprint/nomogram could also successfully stratify the patients into two groups with different recurrence risk (P < 0.05).ConclusionsThe established pre-operative plasma fingerprint/nomogram is efficient in the prediction of recurrence risk, which could facilitate candidate selection in liver transplantation for HCC.     

Repeated inductive heating using a sintered MgFe2O4 needle for minimally invasive local control in breast cancer therapy

Purpose: This study investigated the efficacy of repeated thermotherapy for breast cancer utilising a novel sintered MgFe₂O₄ needle and alternating current (AC) magnetic field in xenograft animal models mimicking human breast cancer.

Materials and methods: A sintered MgFe₂O₄ needle and an apparatus to apply an AC magnetic field were prepared for this study. Animals bearing BT-474 tumours (mean (±standard deviation) volume, 471 ± 153 mm³) were divided into four groups. A sintered MgFe₂O₄ needle (length, 5 mm) was placed in the centre of each tumour. An AC magnetic field (amplitude, 4 kA/m; 2 kW; 540 kHz) was applied for 10 min once, twice or three times for the first, second and third groups, respectively, and was not applied for the control group. Temperature during treatment and tumour volume 8 weeks after first treatment were assessed.

Results: Maximum tumour temperature tended to increase in repeated-application groups: group 1, 59.2 ± 4°C; group 2, 58.9 ± 3.3°C and 61.2 ± 8.9°C for the first and second applications; and group 3, 60.4 ± 4.6°C, 62.1 ± 7.8°C and 71.1 ± 6.1°C for the first, second and third applications. Tumour volumes in control, groups 1, 2 and 3 at 8 weeks after treatment were 3633 ± 2478 mm³, 3240 ± 1031 mm³, 1252 ± 1289 mm³ and 0 mm³, respectively. Tumours were significantly smaller in group 3 than in the control and group 1 at 8 weeks.

Conclusions: The efficacy of repeated inductive heating utilising a sintered MgFe₂O₄ needle was demonstrated. Thermotherapy using the present method may offer an effective non-surgical treatment for human breast cancer.     

思他宁在晚期胃肠道肿瘤患者合并恶性肠梗阻治疗中的应用

Objective:To investigate the effectiveness of stilarnin in malignant bowel obstruction (MBO) due to advanced gastrointestinal carcinoma patients.Methods:62 patients with MBO due to gastrointestinal carcinoma were randomly divided into two groups:routine therapy group (control group 30 patients) and stilamin group (32 patients).Stilamin group received routine therapy combined with stilamin (6 mg/d) by 24 hours continuous infusion for three to twelve days.The curative effectiveness was observed and compared between the two groups.Results:After treatment,the clinical symptoms of abdominal distention and abdominal pain were relieved significantly in stilamin group compared with the control group (84.4% vs 57.6%;P＜0.05).The exhaust of anus was more earlier (62.1% vs 25.6%;P＜0.05),and the average volume of gastrointestinal decompression reduced more rapidly in stilamin group compared with the control group [(216 ± 158) mL/d vs (522 184) mL/d;P＜0.001),smaller and less fluid-air in the intestinal and in the colon at the 81.3% of patients plain abdominal radiography were observed in stilamin group.Quality of life,evaluated with Kamofsky score (57 ± 7 vs 45 ± 9;P＜0.01),was improved significantly.Conclusion:The administration of stilamin,in combination with routine treatment can be very effective in the management of MBO.It can effectively relieve the symptoms of MBO and improve the quality of life in patients.     

Expression and clinical significance of vascular endothelial growth factor in benign and malignant tissues of breast

Objective:To detect the expression of vascular endothelial growth factor(VEGF)and microvessel density(MVD)count in breast benign affection,breast atypical hyperplasia and breast carcinoma in situ,and to clarify the relationship between VEGF expression,MVD and the clinicopathological features of these diseases. Methods:The expression of VEGF and MVD count in 115 cases breast benign diseases(including 40 breast fibroid tumor,40 breast cystic hyperplasia and 35 intraductal papilloma,19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining(SP-method). Results:The positive rate of VEGF in breast benign diseases,breast atypical hyperplasia and breast carcinoma in situ were 21.74%(25/115)、31.58.%(6/19)and 53.13%(17/32)respectively.It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The expression of VEGF increased gradually in the three groups(P＜0.05).The MVD count of the three groups were 14.41±2.59,18.89±4.47 and 21.13±4.12 respectively,It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The MVD count of the three groups increased gradually(P＜0.05).In VEGF positive group,MVD count was 19.41±4.78;In VEGF negative group,MVD count was 14.91±3.15.The MVD count was higher in VEGF positive group than that in VEGF negative group(P＜0.05). Conclusion:The results of this study suggested that VEGF could promote microvessel growth in breast tumors.The occurrence and progression of breast cancer might be related with the expression of VEGF.